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Sample records for preventive peptide lunasin

  1. Antioxidant and anti-inflammatory properties of cancer preventive peptide lunasin in RAW 264.7 macrophages.

    PubMed

    Hernández-Ledesma, Blanca; Hsieh, Chia-Chien; de Lumen, Ben O

    2009-12-18

    Oxidative stress and inflammation are two of the most critical factors implicated in carcinogenesis and other degenerative disorders. We have investigated how lunasin, a known anti-cancer seed peptide, affect these factors. This peptide inhibits linoleic acid oxidation and acts as 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenger. Furthermore, using LPS-stimulated RAW 264.7 macrophages, we have demonstrated that lunasin reduces, in a significant dose-dependent manner, the production of reactive oxygen species (ROS) by LPS-induced macrophages. Lunasin also inhibits the release of pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha] and interleukine-6 [IL-6]). On the basis of these potent antioxidant and anti-inflammatory properties, we propose lunasin not only as a cancer preventive and therapeutic agent but also as an agent against other inflammatory-related disorders.

  2. The protective role of the Bowman-Birk protease inhibitor in soybean lunasin digestion: the effect of released peptides on colon cancer growth.

    PubMed

    Cruz-Huerta, Elvia; Fernández-Tomé, Samuel; Arques, M Carmen; Amigo, Lourdes; Recio, Isidra; Clemente, Alfonso; Hernández-Ledesma, Blanca

    2015-08-01

    Lunasin is a naturally-occurring peptide demonstrating chemopreventive, antioxidant and anti-inflammatory properties. To exhibit these activities, orally ingested lunasin needs to survive proteolytic attack of digestive enzymes to reach target tissues in active form/s. Preliminary studies suggested the protective role of protease inhibitors, such as the Bowman-Birk inhibitor and Kunitz-trypsin inhibitor, against lunasin's digestion by both pepsin and pancreatin. This work describes in depth the behaviour of lunasin under conditions simulating the transit through the gastrointestinal tract in the absence or presence of soybean Bowman-Birk isoinhibitor 1 (IBB1) in both active and inactive states. By liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS), the remaining lunasin at the end of gastric and gastro-duodenal phases was quantified. Protection against the action of pepsin was independent of the amount of IBB1 present in the analyzed samples, whereas an IBB1 dose-dependent protective effect against trypsin and chymotrypsin was observed. Peptides released from lunasin and inactive IBB1 were identified by MS/MS. The remaining lunasin and IBB1 as well as their derived peptides could be responsible for the anti-proliferative activity against colon cancer cells observed for the digests obtained at the end of simulated gastrointestinal digestion.

  3. Lunasin-aspirin combination against NIH/3T3 cells transformation induced by chemical carcinogens.

    PubMed

    Hsieh, Chia-Chien; Hernández-Ledesma, Blanca; de Lumen, Ben O

    2011-06-01

    Carcinogenesis is a multistage process involving a number of molecular pathways sensitive to intervention. Chemoprevention is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combination of two or more chemopreventive agents is commonly considered as a better preventive and/or therapeutic strategy. Lunasin is a promising cancer preventive peptide identified in soybean and other seeds. Its efficacy has been demonstrated by both in vitro and in vivo models. This peptide has been found to inhibit human breast cancer MDA-MB-231 cells proliferation, suppressing cell cycle progress and inducing cell apoptosis. Moreover, lunasin potentiates the effects on these cells of different synthetic and natural compounds, such as aspirin and anacardic acid. This study explored the role of lunasin, alone and in combination with aspirin and anacardic acid on cell proliferation and foci formation of transformed NIH/3T3 cells induced by chemical carcinogens 7,12-dimethylbenz[a]anthracene or 3-methylcholanthrene. The results revealed that lunasin, acting as a single agent, inhibits cell proliferation and foci formation. When combined with aspirin, these effects were significantly increased, indicating that this combination might be a promising strategy to prevent/treat cancer induced by chemical carcinogens.

  4. An effective and simple procedure to isolate abundant quantities of biologically active chemopreventive lunasin-protease inhibitor concentrate (LPIC) from soybean

    USDA-ARS?s Scientific Manuscript database

    Lunasin is a 5-kDa soybean bioactive peptide with demonstrated anti-cancer and anti-inflammatory properties. The use of lunasin as a chemopreventive agent in large-scale animal studies and human clinical trials is hampered by the paucity of large quantities of lunasin. Recently, purification methods...

  5. Oral Administration of CardioAid and Lunasin Alleviates Liver Damage in a High-Fat Diet Nonalcoholic Steatohepatitis Model.

    PubMed

    Drori, Ariel; Rotnemer-Golinkin, Dvorah; Zolotarov, Lidya; Ilan, Yaron

    2017-01-01

    Several of the drugs in development for treatment of nonalcoholic steatohepatitis (NASH) target liver fibrosis or have side effects that prohibit their long-term use in patients with mild to moderate disease. Lunasin is a soy-derived peptide with anti-inflammatory properties. ADM's CardioAid™ is a plant sterol extract that exerts cholesterol- and triacylglycerol-lowering effects. To determine the immunomodulatory effects of CardioAid and lunasin in a high-fat diet (HFD) animal model of NASH. C57BL/6 mice on an HFD were orally administered CardioAid or lunasin for 25 weeks. The effects on the immune system, liver function, insulin resistance and lipid profile were studied. Treatment with CardioAid and lunasin was associated with a significant decrease in the CD4/CD8 ratio and an increase in CD4+CD25+ lymphocytes. A decrease in interleukin 1-alpha serum levels and an increase in transforming growth factor beta serum levels were noted. These were associated with alleviation of liver damage as indicated by a significant decrease in liver enzymes and improvement in the histological nonalcoholic fatty liver disease activity score (NAS). Decreases in both serum triglyceride and serum glucose levels were observed in treated mice. A decrease in total body fat measured by EchoMRI was also observed in treated mice. CardioAid and lunasin exerted hepatoprotective and glucose-protective effects in an HFD NASH model. These data and the high-safety profiles of CardioAid and Lunasin support their use in patients in the early stages of NASH to prevent deterioration due to the disease. © 2017 S. Karger AG, Basel.

  6. Efficient production of native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein system in Escherichia coli.

    PubMed

    Setrerrahmane, Sarra; Zhang, Yi; Dai, Guangzhi; Lv, Jing; Tan, Shuhua

    2014-09-01

    To develop an efficient and cost-effective approach for the production of small preventive peptide lunasin with correct natural N terminus, a synthetic gene was designed by OPTIMIZER & Gene Designer and cloned into pTWIN1 vector at SapI and PstI sites. Thus, lunasin was N-terminally fused to the pH-induced self-cleavable Ssp DnaB mini-intein linked to a chitin binding domain (CBD) with no extra residues. The resultant fusion protein was highly expressed by lactose induction in Escherichia coli BL21 (DE3) in a 7-l bioreactor and bound to a chitin affinity column. After washing the impurities, the Ssp DnaB intein mediated on-column self-cleavage was easily triggered by shifting pH and temperature to allow the native lunasin released. The final purified lunasin yielded up to 75 mg/l medium. Tricine/SDS-PAGE and matrix-assisted laser desorption time-of-flight (MALDI-TOF)/mass spectrometry (MS) verified the structural authenticity of the product, implying the correct cleavage at the junction between Ssp DnaB intein and lunasin. MTT assay confirmed its potent proliferation inhibitory activity to human cancer cells HCT-116 and MDA-MB-231; however, no cytotoxicity to normal human lens epithelial cell SRA01/04 and hepatoma HepG2. Taken together, we provide a novel strategy to produce recombinant native lunasin with correct N-terminal processing by using the pH-induced self-cleavable Ssp DnaB mini-intein.

  7. Lunasin, with an arginine-glycine-aspartic acid motif, causes apoptosis to L1210 leukemia cells by activation of caspase-3.

    PubMed

    de Mejia, Elvira Gonzalez; Wang, Wenyi; Dia, Vermont P

    2010-03-01

    Lunasin is a novel chemopreventive peptide featuring a cell adhesion motif composed of arginine-glycine-aspartate (RGD) which has been associated to cytotoxicity to established cell lines. The objectives of this study were to determine the effect of lunasin on the viability of L1210 leukemia cells and to understand the underlying mechanisms involved. Pure lunasin and lunasin enriched soy flour (LES) caused cytotoxicity to L1210 leukemia cells with IC(50) of 14 and 16 microM (lunasin equivalent), respectively. Simulated gastrointestinal digestion showed that 25% of the original amount of lunasin survived 3 h of pepsin digestion and 3% of lunasin remained after sequential pepsin-pancreatin digestion for a total of 6 h. Cell cycle analysis showed that lunasin caused a dose-dependent G2 cell cycle arrest and apoptosis. Treatment of L1210 leukemia cells with 1 mg/mL of LES for 18 h led to an increase in the amount of apoptotic cells from 2 to 40%. Compared to untreated cells, treatment with 1 mg/mL LES showed a 6-fold increase on the expressions of caspases-8 and -9, and and a 12-fold increase on the expression of caspase-3. These results showed for the first time that lunasin, a naturally occurring peptide containing an RGD motif, caused apoptosis to L1210 leukemia cells through caspase-3 activation.

  8. Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis.

    PubMed

    Price, Samuel J; Pangloli, Philipus; Krishnan, Hari B; Dia, Vermont P

    2016-12-01

    Soybean contains several biologically active components and one of this belongs to the bioactive peptide group. The objectives of this study were to produce different lunasin-enriched preparations (LEP) and determine the effect of Bowman-Birk inhibitor (BBI) and Kunitz trypsin inhibitor (KTI) concentrations on the stability of lunasin against pepsin-pancreatin hydrolysis (PPH). In addition, the effect of KTI mutation on lunasin stability against PPH was determined. LEP were produced by calcium and pH precipitation methods of 30% aqueous ethanol extract from defatted soybean flour. LEP, lunasin-enriched commercially available products and KTI control and mutant flours underwent PPH and samples were taken after pepsin and pepsin-pancreatin hydrolysis. The concentrations of BBI, KTI, and lunasin all decreased after hydrolysis, but they had varying results. BBI concentration ranged from 167.5 to 655.8μg/g pre-hydrolysis and 171.5 to 250.1μg/g after hydrolysis. KTI concentrations ranged from 0.3 to 122.3μg/g pre-hydrolysis and 9.0 to 18.7μg/g after hydrolysis. Lunasin concentrations ranged from 8.5 to 71.0μg/g pre-hydrolysis and 4.0 to 13.2μg/g after hydrolysis. In all products tested, lunasin concentration after PPH significantly correlated with BBI and KTI concentrations. Mutation in two KTI isoforms led to a lower concentration of lunasin after PPH. This is the first report on the potential role of KTI in lunasin stability against PPH and must be considered in designing lunasin-enriched products that could potentially survive digestion after oral ingestion. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms.

    PubMed

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P; Sze, Siu Kwan

    2016-05-18

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer's health and risk of chronic diseases.

  10. Commercial processed soy-based food product contains glycated and glycoxidated lunasin proteoforms

    PubMed Central

    Serra, Aida; Gallart-Palau, Xavier; See-Toh, Rachel Su-En; Hemu, Xinya; Tam, James P.; Sze, Siu Kwan

    2016-01-01

    Nutraceuticals have been proposed to exert positive effects on human health and confer protection against many chronic diseases. A major bioactive component of soy-based foods is lunasin peptide, which has potential to exert a major impact on the health of human consumers worldwide, but the biochemical features of dietary lunasin still remain poorly characterized. In this study, lunasin was purified from a soy-based food product via strong anion exchange solid phase extraction and then subjected to top-down mass spectrometry analysis that revealed in detail the molecular diversity of lunasin in processed soybean foods. We detected multiple glycated proteoforms together with potentially toxic advanced glycation end products (AGEs) derived from lunasin. In both cases, modification sites were Lys24 and Lys29 located at the helical region that shows structural homology with a conserved region of chromatin-binding proteins. The identified post-translational modifications may have an important repercussion on lunasin epigenetic regulatory capacity. Taking together, our results demonstrate the importance of proper chemical characterization of commercial processed food products to assess their impact on consumer’s health and risk of chronic diseases. PMID:27189269

  11. Kunitz trypsin inhibitor in addition to Bowman-Birk inhibitor influence stability of lunasin against pepsin-pancreatin hydrolysis

    USDA-ARS?s Scientific Manuscript database

    Soybean contains several biologically active components and one of this belongs to the bioactive peptide group. The objectives of this study were to produce different lunasin-enriched preparations (LEP) and determine the effect of Bowman-Birk inhibitor and Kunitz trypsin concentrations on the stabil...

  12. The Effect of Lunasin on Receptor Activator of Nuclear Factor Kappa-B Ligand-mediated Osteoclast Formation from RAW 264.7 Cells.

    PubMed

    Bachala, Daisy; El-Refai, Nivine; Greenfield, Edward; Aminoshariae, Anita; Mickel, Andre

    2018-06-01

    To date, no study has investigated the antiresorptive property of lunasin. Hence, the present study aimed to assess the ability of lunasin to inhibit the osteoclast formation using RAW 264.7 cells. We hypothesized that lunasin is able to inhibit osteoclast formation. In the present study, the murine monocytic cell line RAW 264.7 was induced to differentiate into mature osteoclasts in the presence of recombinant receptor activator of nuclear factor kappa-B ligand. Tartrate-resistant acid phosphatase, a marker of osteoclasts, was used to identify osteoclasts. Cell lines were divided into different groups and exposed to different concentrations of 50 μmol/L, 75 μmol/L, and 100 μmol/L active and inactive lunasin. The control group was RAW 264.7 cells with receptor activator of nuclear factor kappa-B ligand. Tartrate-resistant acid phosphatase-positive cells of 3 or more nuclei, indicative of mature osteoclasts, were counted by 3 observers. The mean number of the data collected was analyzed using 1-way analysis of variance and the multiple comparison post hoc Bonferroni correction. There was a significant difference in the reduction of osteoclast formation in all the active lunasin groups (P < .001) compared with the control group and the inactive lunasin group (P < .001). Considering the suppressive effect of lunasin on osteoclastogenesis, the use of lunasin as a potential antiresorptive agent can be evaluated in future studies. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  13. Bioactive Peptide of Marine Origin for the Prevention and Treatment of Non-Communicable Diseases

    PubMed Central

    Pangestuti, Ratih; Kim, Se-Kwon

    2017-01-01

    Non-communicable diseases (NCD) are the leading cause of death and disability worldwide. The four main leading causes of NCD are cardiovascular diseases, cancers, respiratory diseases and diabetes. Recognizing the devastating impact of NCD, novel prevention and treatment strategies are extensively sought. Marine organisms are considered as an important source of bioactive peptides that can exert biological functions to prevent and treatment of NCD. Recent pharmacological investigations reported cardio protective, anticancer, antioxidative, anti-diabetic, and anti-obesity effects of marine-derived bioactive peptides. Moreover, there is available evidence supporting the utilization of marine organisms and its bioactive peptides to alleviate NCD. Marine-derived bioactive peptides are alternative sources for synthetic ingredients that can contribute to a consumer’s well-being, as a part of nutraceuticals and functional foods. This contribution focus on the bioactive peptides derived from marine organisms and elaborates its possible prevention and therapeutic roles in NCD. PMID:28282929

  14. Diet-influenced chromatin modification and expression of chemopreventive genes by the soy peptide, lunasin

    USDA-ARS?s Scientific Manuscript database

    Epigenetic silencing of tumor suppressors and pro-apoptosis genes in cancer cells, unlike genetic mutations, can potentially be reversed by the use of DNA demethylating agents (to remove methylation marks on the DNA) and HDAC inhibitors (to increase histone acetylation). It is now well established t...

  15. Peptide vaccines prevent tumor growth by activating T cells that respond to native tumor antigens.

    PubMed

    Jordan, Kimberly R; McMahan, Rachel H; Kemmler, Charles B; Kappler, John W; Slansky, Jill E

    2010-03-09

    Peptide vaccines enhance the response of T cells toward tumor antigens and represent a strategy to augment antigen-independent immunotherapies of cancer. However, peptide vaccines that include native tumor antigens rarely prevent tumor growth. We have assembled a set of peptide variants for a mouse-colon tumor model to determine how to improve T-cell responses. These peptides have similar affinity for MHC molecules, but differ in the affinity of the peptide-MHC/T-cell receptor interaction with a tumor-specific T-cell clone. We systematically demonstrated that effective antitumor responses are generated after vaccination with variant peptides that stimulate the largest proportion of endogenous T cells specific for the native tumor antigen. Importantly, we found some variant peptides that strongly stimulated a specific T-cell clone in vitro, but elicited fewer tumor-specific T cells in vivo, and were not protective. The T cells expanded by the effective vaccines responded to the wild-type antigen by making cytokines and killing target cells, whereas most of the T cells expanded by the ineffective vaccines only responded to the peptide variants. We conclude that peptide-variant vaccines are most effective when the peptides react with a large responsive part of the tumor-specific T-cell repertoire.

  16. C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy.

    PubMed

    Bhatt, Mahendra Prasad; Lim, Young-Cheol; Ha, Kwon-Soo

    2014-11-01

    Lack of C-peptide, along with insulin, is the main feature of Type 1 diabetes mellitus (DM) and is also observed in progressive β-cell loss in later stage of Type 2 DM. Therapeutic approaches to hyperglycaemic control have been ineffective in preventing diabetic vasculopathy, and alternative therapeutic strategies are necessary to target both hyperglycaemia and diabetic complications. End-stage organ failure in DM seems to develop primarily due to vascular dysfunction and damage, leading to two types of organ-specific diseases, such as micro- and macrovascular complications. Numerous studies in diabetic patients and animals demonstrate that C-peptide treatment alone or in combination with insulin has physiological functions and might be beneficial in preventing diabetic complications. Current evidence suggests that C-peptide replacement therapy might prevent and ameliorate diabetic vasculopathy and organ-specific complications through conservation of vascular function, as well as prevention of endothelial cell death, microvascular permeability, vascular inflammation, and neointima formation. In this review, we describe recent advances on the beneficial role of C-peptide replacement therapy for preventing diabetic complications, such as retinopathy, nephropathy, neuropathy, impaired wound healing, and inflammation, and further discuss potential beneficial effects of combined C-peptide and insulin supplement therapy to control hyperglycaemia and to prevent organ-specific complications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  17. Melanoma prevention by MC1R selective small peptide analogs of alpha MSH | Division of Cancer Prevention

    Cancer.gov

    This revised application will test the hypothesis that small peptide analogs of ¿-melanocortin (¿-MSH) that are selective agonists of the melanocortin 1 receptor (MC1R) will prevent melanoma tumor formation in transgenic mouse melanoma models by enhancing repair of ultraviolet radiation (UV)-induced DNA damage and stimulating melanogenesis. We have pioneered the research on

  18. A Chimeric Peptide Composed of a Dermaseptin Derivative and an RNA III-Inhibiting Peptide Prevents Graft-Associated Infections by Antibiotic-Resistant Staphylococci

    PubMed Central

    Balaban, Naomi; Gov, Yael; Giacometti, Andrea; Cirioni, Oscar; Ghiselli, Roberto; Mocchegiani, Federico; Orlando, Fiorenza; D'Amato, Giuseppina; Saba, Vittorio; Scalise, Giorgio; Bernes, Sabina; Mor, Amram

    2004-01-01

    Staphylococcal bacteria are a prevalent cause of infections associated with foreign bodies and indwelling medical devices. Bacteria are capable of escaping antibiotic treatment through encapsulation into biofilms. RNA III-inhibiting peptide (RIP) is a heptapeptide that inhibits staphylococcal biofilm formation by obstructing quorum-sensing mechanisms. K4-S4(1-13)a is a 13-residue dermaseptin derivative (DD13) believed to kill bacteria via membrane disruption. We tested each of these peptides as well as a hybrid construct, DD13-RIP, for their ability to inhibit bacterial proliferation and suppress quorum sensing in vitro and for their efficacy in preventing staphylococcal infection in a rat graft infection model with methicillin-resistant Staphylococcus aureus (MRSA) or S. epidermidis (MRSE). In vitro, proliferation assays demonstrated that RIP had no inhibitory effect, while DD13-RIP and DD13 were equally effective, and that the chimeric peptide but not DD13 was slightly more effective than RIP in inhibiting RNA III synthesis, a regulatory RNA molecule important for staphylococcal pathogenesis. In vivo, the three peptides reduced graft-associated bacterial load in a dose-dependent manner, but the hybrid peptide was most potent in totally preventing staphylococcal infections at the lowest dose. In addition, each of the peptides acted synergistically with antibiotics. The data indicate that RIP and DD13 act in synergy by attacking bacteria simultaneously by two different mechanisms. Such a chimeric peptide may be useful for coating medical devices to prevent drug-resistant staphylococcal infections. PMID:15215107

  19. C-peptide prevents SMAD3 binding to alpha promoters to inhibit collagen type IV synthesis.

    PubMed

    Li, Yanning; Zhong, Yan; Gong, Wenjian; Gao, Xuehan; Qi, Huanli; Liu, Kun; Qi, Jinsheng

    2018-07-01

    Activation of transforming growth factor β1 (TGFB1)/SMAD3 signaling may lead to additional synthesis of collagen type IV (COL4), which is a major contributor to extracellular matrix (ECM) accumulation in diabetic nephropathy (DN). C-peptide can attenuate fibrosis to have unique beneficial effects in DN. However, whether and how C-peptide affects TGFB1/SMAD3-activated COL4 synthesis is unclear. In this study, pathological changes, expression of COL4 a1-a5 chains ( Col4a1-a5 ), COL4 distribution and protein and TGFB1 and SMAD3 protein were first assessed in a rat model of diabetes. Then, rat mesangial cells were treated with high glucose (HG) and/or C-peptide to investigate the underlying mechanism. Col4a1-a5 expression, COL4 protein and secretion, TGFB1 protein, SMAD3 nuclear translocation and binding of SMAD3 to its cognate sites in the promoters of Col4a1a2 , Col4a3a4 and Col4a5 were measured. It was found that C-peptide attenuated glomerular pathological changes and suppressed renal Col4a1 -a5 mRNA expression, COL4 protein content and TGFB1 protein content. C-peptide had a dose-dependent effect to inhibit Col4a1-a5 mRNA expression, COL4 protein content and secretion, in HG-stimulated mesangial cells. In addition, the HG-induced increase in TGFB1 protein content was significantly reduced by C-peptide. Although not apparently affecting SMAD3 nuclear translocation, C-peptide prevented SMAD3 from binding to its sites in the Col4a1a2 , Col4a3a4 and Col4a5 promoters in HG-stimulated mesangial cells. In conclusion, C-peptide could prevent SMAD3 from binding to its sites in the Col4a1a2 , Col4a3a4 and Col4a5 promoters, to inhibit COL4 generation. These results may provide a mechanism for the alleviation of fibrosis in DN by C-peptide. © 2018 Society for Endocrinology.

  20. Tumstatin peptide, an inhibitor of angiogenesis, prevents glomerular hypertrophy in the early stage of diabetic nephropathy.

    PubMed

    Yamamoto, Yoshihiko; Maeshima, Yohei; Kitayama, Hiroyuki; Kitamura, Shinji; Takazawa, Yuki; Sugiyama, Hitoshi; Yamasaki, Yasushi; Makino, Hirofumi

    2004-07-01

    In the early stage of diabetic nephropathy (one of the major microvascular complications of diabetes) glomerular hyperfiltration and hypertrophy are observed. It is clinically important to regulate glomerular hypertrophy for preventing glomerulosclerosis. The number of glomerular endothelial cells is known to be increased in diabetic nephropathy associated with enlarged glomerular tufts, suggesting that the mechanism is similar to that of angiogenesis. Tumstatin peptide is an angiogenesis inhibitor derived from type IV collagen and inhibits in vivo neovascularization induced by vascular endothelial growth factor (VEGF), one of the mediators of glomerular hypertrophy in diabetic nephropathy. Here, we show the effect of tumstatin peptide in inhibiting alterations in early diabetic nephropathy. Glomerular hypertrophy, hyperfiltration, and albuminuria were suppressed by tumstatin peptide (1 mg/kg) in streptozotocin-induced diabetic mice. Glomerular matrix expansion, the increase of total glomerular cell number and glomerular endothelial cells (CD31 positive), and monocyte/macrophage accumulation was inhibited by tumstatin peptide. Increase in renal expression of VEGF, flk-1, and angiopoietin-2, an antagonist of angiopoietin-1, was inhibited by tumstatin treatment in diabetic mice. Alteration of glomerular nephrin expression, a podocyte protein crucial for maintaining glomerular filtration barrier, was recovered by tumstatin in diabetic mice. Taken together, these results demonstrate the potential use of antiangiogenic tumstatin peptide as a novel therapeutic agent in early diabetic nephropathy.

  1. Sequestration of the Aβ Peptide Prevents Toxicity and Promotes Degradation In Vivo

    PubMed Central

    de Barros, Teresa Pereira; van Dijk Härd, Iris; Brorsson, Ann-Christin; Macao, Bertil; Persson, Cecilia; Crowther, Damian C.; Lomas, David A.; Ståhl, Stefan; Dobson, Christopher M.; Härd, Torleif

    2010-01-01

    Protein aggregation, arising from the failure of the cell to regulate the synthesis or degradation of aggregation-prone proteins, underlies many neurodegenerative disorders. However, the balance between the synthesis, clearance, and assembly of misfolded proteins into neurotoxic aggregates remains poorly understood. Here we study the effects of modulating this balance for the amyloid-beta (Aβ) peptide by using a small engineered binding protein (ZAβ3) that binds with nanomolar affinity to Aβ, completely sequestering the aggregation-prone regions of the peptide and preventing its aggregation. Co-expression of ZAβ3 in the brains of Drosophila melanogaster expressing either Aβ42 or the aggressive familial associated E22G variant of Aβ42 abolishes their neurotoxic effects. Biochemical analysis indicates that monomer Aβ binding results in degradation of the peptide in vivo. Complementary biophysical studies emphasize the dynamic nature of Aβ aggregation and reveal that ZAβ3 not only inhibits the initial association of Aβ monomers into oligomers or fibrils, but also dissociates pre-formed oligomeric aggregates and, although very slowly, amyloid fibrils. Toxic effects of peptide aggregation in vivo can therefore be eliminated by sequestration of hydrophobic regions in monomeric peptides, even when these are extremely aggregation prone. Our studies also underline how a combination of in vivo and in vitro experiments provide mechanistic insight with regard to the relationship between protein aggregation and clearance and show that engineered binding proteins may provide powerful tools with which to address the physiological and pathological consequences of protein aggregation. PMID:20305716

  2. Prevention of ESKAPE pathogen biofilm formation by antimicrobial peptides WLBU2 and LL37.

    PubMed

    Lin, Qiao; Deslouches, Berthony; Montelaro, Ronald C; Di, Y Peter

    2018-05-09

    Bacterial biofilm-dependent infections (e.g., cystic fibrosis, surgical sites, and medical implants) are associated with enhanced drug-resistance and thus difficult to eradicate. The goal of this study was to systematically compare three distinct classes of antimicrobial peptides (AMPs) that include the clinically used antibiotic colistin, the natural AMP LL37, the engineered cationic-AMP WLBU2, and four commonly used antibiotics with different bactericidal mechanisms (tobramycin, ciprofloxacin, ceftazidime and vancomycin) for biofilm prevention properties. Using biofilm-prevention assays, we detected bacterial biomass post-attachment in subinhibitory concentrations (1/3 of the MIC) for each AMP, by the crystal violet method, to distinguish the commonly known bactericidal from potentially distinct mechanisms of biofilm prevention. Biofilm regulatory gene expression was assessed using RT-qPCR for correlation with biofilm growth inhibition. Commonly used antibiotics at 1x MIC showed modest ESKAPE biofilm prevention while 1/3 MIC of AMPs demonstrated up to 90% of biofilm prevention. WLBU2 was generally more effective in preventing bacterial attachment than colistin and LL37. Changes in expression of bacterial genes known to affect biofilm regulation were consistent with biofilm prevention. The data warrant further exploration of AMPs with optimized structures to fill a knowledge gap on the potential application of AMPs to difficult-to-cure bacterial biofilm-related infections. Copyright © 2018. Published by Elsevier B.V.

  3. Vasoactive intestinal peptide prevents lung injury due to xanthine/xanthine oxidase.

    PubMed

    Berisha, H; Foda, H; Sakakibara, H; Trotz, M; Pakbaz, H; Said, S I

    1990-08-01

    Reactive oxygen species mediate injury and inflammation in many tissues. The addition of xanthine and xanthine oxidase to perfused rat lungs led to increases in peak airway pressure and perfusion pressure, pulmonary edema, and increased protein content in bronchoalveolar lavage fluid. Treatment with 1-10 micrograms.kg-1.min-1 of vasoactive intestinal peptide (VIP), a widely distributed neuropeptide, markedly reduced or totally prevented all signs of injury. Simultaneously, VIP also diminished or abolished the associated generation of arachidonate products. Similar protection was provided by catalase (100 micrograms/ml) but not by the VIP-related peptides secretin or glucagon. The pulmonary vasodilator papaverine (0.15 mg/ml) was also ineffective. Injured lungs that were not treated with VIP released large amounts of this peptide in the perfusate. The results indicate that VIP has potent protective activity against injury triggered by xanthine/xanthine oxidase and may be a physiological modulator of inflammatory tissue damage associated with toxic oxygen metabolites.

  4. Evolving Use of Natriuretic Peptides as Part of Strategies for Heart Failure Prevention.

    PubMed

    McDonald, Ken; Wilkinson, Mark

    2017-01-01

    Heart failure (HF) remains one of the major cardiovascular challenges to the Western world. Once established, HF is characterized by compromised life expectancy and quality of life with considerable dependence on hospital care for episodic clinical deterioration. Much is understood about the risk factors that predispose to the development of HF. With such a broad range of factors, it is clear that there is a large population at risk, potentially in excess of 25% of the adult population. Therein lies the major challenge at the outset of our efforts to prevent HF. With such a large population at risk, how do we develop an effective prevention strategy? HF prevention requires a multimodal approach. In this review, we focus primarily on the role of natriuretic peptide (NP) as a tool in a prevention strategy. Prevention of HF is a major public health challenge, underlined by the concerning epidemiological trends, the associated costs, and the continued difficulty to find effective therapies for the growing number of patients with preserved systolic function HF. Population-based approaches focusing on lifestyle and risk factor control have made some impact but not to a satisfactory level and also tend to result in a uniform approach across a population with different risk profiles. Individualizing risk is therefore required, with emerging data indicating that NP-guided risk stratification and intervention can reduce downstream incident HF and other cardiovascular events. © 2016 American Association for Clinical Chemistry.

  5. Kefir Peptides Prevent Hyperlipidemia and Obesity in High-Fat-Diet-Induced Obese Rats via Lipid Metabolism Modulation.

    PubMed

    Tung, Yu-Tang; Chen, Hsiao-Ling; Wu, Hsin-Shan; Ho, Mei-Hsuan; Chong, Kowit-Yu; Chen, Chuan-Mu

    2018-02-01

    Obesity has reached epidemic proportions worldwide. Obesity is a complex metabolic disorder that is linked to numerous serious health complications with high morbidity. The present study evaluated the effects of kefir peptides on high fat diet (HFD)-induced obesity in rats. Kefir peptides markedly improved obesity, including body weight gain, inflammatory reactions and the formation of adipose tissue fat deposits around the epididymis and kidney, and adipocyte size. Treating high fat diet (HFD)-induced obese rats with kefir peptides significantly reduced the fatty acid synthase protein and increased the p-acetyl-CoA carboxylase protein to block lipogenesis in the livers. Kefir peptides also increased fatty acid oxidation by increasing the protein expressions of phosphorylated AMP-activated protein kinase, peroxisome proliferator-activated receptor-α, and hepatic carnitine palmitoyltransferase-1 in the livers. In addition, administration of kefir peptides significantly decreased the inflammatory response (TNF-α, IL-1β, and TGF-β) to modulate oxidative damage. These results demonstrate that kefir peptides treatment improves obesity via inhibition of lipogenesis, modulation of oxidative damage, and stimulation of lipid oxidation. Therefore, kefir peptides may act as an anti-obesity agent to prevent body fat accumulation and obesity-related metabolic diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Evaluation of free or anchored antimicrobial peptides as candidates for the prevention of orthopaedic device-related infections.

    PubMed

    D'Este, Francesca; Oro, Debora; Boix-Lemonche, Gerard; Tossi, Alessandro; Skerlavaj, Barbara

    2017-10-01

    The prevention of implant-associated infection, one the most feared complications in orthopaedic surgery, remains a major clinical challenge and urges development of effective methods to prevent bacterial colonization of implanted devices. Alpha-helical antimicrobial peptides (AMPs) may be promising candidates in this respect due to their potent and broad-spectrum antimicrobial activity, their low tendency to elicit resistance and possible retention of efficacy in the immobilized state. The aim of this study was to evaluate the potential of five different helical AMPs, the cathelicidins BMAP-27 and BMAP-28, their (1-18) fragments and the rationally designed, artificial P19(9/G7) peptide, for the prevention of orthopaedic implant infections. Peptides were effective at micromolar concentrations against 22 Staphylococcus and Streptococcus isolates from orthopaedic infections, while only BMAP-28 and to a lesser extent BMAP-27 were active against Enterococcus faecalis. Peptides in solution showed activities comparable to those of cefazolin and linezolid, on a molar basis, and also a variable capacity to neutralize bacterial lipopolysaccharide, while devoid of adverse effects on MG-63 osteoblast cells at concentrations corresponding to the MIC. The (1-18) BMAP fragments and P19(9/G7) were selected for further examination, based on better selectivity indices, and showed effectiveness in the presence of hyaluronic acid and in synovial fluid, while human serum affected their activity to variable extents, with BMAP-27(1-18) best retaining activity. This peptide was immobilized on streptavidin-resin beads and retained activity against reference Staphylococcus epidermidis and Staphylococcus aureus strains, with negligible toxicity towards osteoblasts, underlining its potential for the development of infection-resistant biomaterials for orthopaedic application. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and

  7. Insect antimicrobial peptides: potential tools for the prevention of skin cancer.

    PubMed

    Tonk, Miray; Vilcinskas, Andreas; Rahnamaeian, Mohammad

    2016-09-01

    Antimicrobial peptides/proteins (AMPs) are biologically active molecules with diverse structural properties that are produced by mammals, plants, insects, ticks, and microorganisms. They have a range of antibacterial, antifungal, antiviral, and even anticancer activities, and their biological properties could therefore be exploited for therapeutic and prophylactic applications. Cancer and cancer drug resistance are significant current health challenges, so the development of innovative cancer drugs with minimal toxicity toward normal cells and novel modes of action that can evade resistance may provide a new direction for anticancer therapy. The skin is the first line of defense against heat, sunlight, injury, and infection, and skin cancer is thus the most common type of cancer. The skin that has been exposed to sunlight is particularly susceptible, but lesions can occur anywhere on the body. Skin cancer awareness and self-efficacy are necessary to improve sun protection behavior, but more effective preventative approaches are also required. AMPs may offer a new prophylactic approach against skin cancer. In this mini review, we draw attention to the potential use of insect AMPs for the prevention and treatment of skin cancer.

  8. Whey-hydrolyzed peptide-enriched immunomodulating diet prevents progression of liver cirrhosis in rats.

    PubMed

    Jobara, Kanta; Kaido, Toshimi; Hori, Tomohide; Iwaisako, Keiko; Endo, Kosuke; Uchida, Yoichiro; Uemoto, Shinji

    2014-10-01

    Liver fibrosis and subsequent cirrhosis is a major cause of death worldwide, but few effective antifibrotic therapies are reported. Whey-hydrolyzed peptide (WHP), a major peptide component of bovine milk, exerts anti-inflammatory effects in experimental models. A WHP-enriched diet is widely used for immunomodulating diets (IMD) in clinical fields. However, the effects of WHP on liver fibrosis remain unknown. The aim of this study was to investigate the antifibrotic effects of WHP in a rat cirrhosis model. Progressive liver fibrosis was induced by repeated intraperitoneal administration of dimethylnitrosamine (DMN) for 3 wk. Rats were fed either a WHP-enriched IMD (WHP group) or a control enteral diet (control group). The degree of liver fibrosis was compared between groups. Hepatocyte-protective effects were examined using hepatocytes isolated from rats fed a WHP diet. Reactive oxygen species and glutathione in liver tissue were investigated in the DMN cirrhosis model. Macroscopic and microscopic progression of liver fibrosis was remarkably suppressed in the WHP group. Elevated serum levels of liver enzymes and hyaluronic acid, and liver tissue hydroxyproline content were significantly attenuated in the WHP group. Necrotic hepatocyte rates with DMN challenge, isolated from rats fed a WHP-enriched IMD, were significantly lower. In the DMN cirrhosis model, reactive oxygen species were significantly lower, and glutathione was significantly higher in the WHP group's whole liver tissue. A WHP-enriched IMD effectively prevented progression of DMN-induced liver fibrosis in rats via a direct hepatocyte-protective effect and an antioxidant effect through glutathione synthesis. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Administration of bovine casein-derived peptide prevents cognitive decline in Alzheimer disease model mice.

    PubMed

    Min, Li-Juan; Kobayashi, Yodai; Mogi, Masaki; Tsukuda, Kana; Yamada, Akio; Yamauchi, Koji; Abe, Fumiaki; Iwanami, Jun; Xiao, Jin-Zhong; Horiuchi, Masatsugu

    2017-01-01

    There is a growing interest in identifying natural food ingredients that may serve to prevent dementia such as that due to Alzheimer disease (AD). Peptides derived from food proteins have been demonstrated to have various physiological activities such as a hypotensive action. Recent findings have indicated possible associations of hypertension with AD progression, and suggest that angiotensin converting enzyme (ACE) inhibitors with potential to pass through the blood brain barrier (BBB) may reduce the risk of AD. In this study, we investigated the effect of milk peptide (CH-3) on cognitive function in AD model mice. CH-3 contains a tripeptide (methionine-lysine-proline, MKP) that has been found to have a strong ACE inhibitory effect and the potential to pass through the BBB. Adult male ddY mice were used in this study, and an animal model of AD was induced by intracerebroventricular (ICV) injection of Aβ1-42. CH-3 (250 mg/kg/day) or MKP (0.5 mg/kg/day) was orally administered every day starting 2 days before ICV injection. At 3 weeks after ICV injection, cognitive function was evaluated by the Morris water maze test. Brain samples were obtained after behavioral testing, and expression of inflammatory cytokines and NADPH oxidase subunits was measured by real-time quantitative RT-PCR. ICV injection of Aβ1-42 significantly impaired cognitive function compared with that in PBS-injected mice. Daily administration of CH-3 markedly attenuated this Aβ1-42-induced cognitive decline. Aβ1-42 injection significantly enhanced the expression of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS) and p22phox in the mouse hippocampus compared with PBS injection, and showed a tendency to increase the expression of monocyte chemoattractant protein-1 (MCP-1), p47phox and gp91phox, whereas CH-3 treatment markedly reduced Aβ1-42-induced TNF-α, MCP-1, iNOS, p47phox and gp91phox expression. Finally, administration of MKP also attenuated Aβ1-42-induced

  10. Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

    PubMed Central

    Tan, Xiao Wei; Goh, Tze Wei; Saraswathi, P.; Nyein, Chan Lwin; Setiawan, Melina; Riau, Andri; Lakshminarayanan, R.; Liu, Shouping; Tan, Donald; Beuerman, Roger W.

    2014-01-01

    Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection. PMID:24957820

  11. Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.

    PubMed

    Walford, Geoffrey A; Ma, Yong; Christophi, Costas A; Goldberg, Ronald B; Jarolim, Petr; Horton, Edward; Mather, Kieren J; Barrett-Connor, Elizabeth; Davis, Jaclyn; Florez, Jose C; Wang, Thomas J

    2014-05-01

    We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP). The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887). At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

  12. PLGA nanoparticles loaded with beta-lactoglobulin-derived peptides modulate mucosal immunity and may facilitate cow's milk allergy prevention.

    PubMed

    Kostadinova, Atanaska I; Middelburg, Jim; Ciulla, Michele; Garssen, Johan; Hennink, Wim E; Knippels, Leon M J; van Nostrum, Cornelus F; Willemsen, Linette E M

    2018-01-05

    Beta-lactoglobulin (BLG)-derived peptides may facilitate oral tolerance to whey and prevent cow's milk allergy (CMA). Loading of BLG-peptides in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Pep-NP) may improve this. Here we studied the uptake of NP and the capacity of NP and Pep-NP to activate bone marrow dendritic cells (BMDC). Furthermore, CMA prevention was evaluated by orally exposing three-week-old female C3H/HeOuJ mice to Pep-NP, NP or free peptides (PepMix) for 6 days before oral sensitization with whole whey protein and effects on the spleen and small intestine lamina propria (SI-LP) were studied. In BMDC, NP and Pep-NP enhanced CD40 expression and IL-6 and TNF-α secretion, while tended to decrease CD80 expression and prevented PepMix-induced IL-12 secretion. In vivo, oral exposure to Pep-NP, but not NP or PepMix, prior to whey sensitization tended to partially prevent the acute allergic skin response to whole whey protein. Splenocytes of NP-pre-exposed mice secreted increased levels of whey-specific IL-6, but this was silenced in Pep-NP-pre-exposed mice which also showed reduced TNF-α and IFN-γ secretion. In the SI-LP, Pep-NP pre-exposure reduced the CD4 + T cell frequency in CMA mice compared to PBS pre-exposure. In addition, while NP increased whey-specific IL-6 secretion in the SI-LP, Pep-NP did not and maintained regulatory TGF-β secretion. This study presents a proof-of-concept that PLGA nanoparticles facilitate the capacity of BLG peptides to suppress the allergic response to whole whey protein. Hence, PLGA nanoparticles may be further developed as an adjunct strategy for BLG-peptide-based oral tolerance induction and CMA prevention. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation.

    PubMed

    Stathopoulos, Panagiotis; Papas, Serafim; Tsikaris, Vassilios

    2006-03-01

    Decomposition of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

  14. Inhibition of the Electrostatic Interaction between β -amyloid Peptide and Membranes Prevents β -amyloid-induced Toxicity

    NASA Astrophysics Data System (ADS)

    Hertel, C.; Terzi, E.; Hauser, N.; Jakob-Rotne, R.; Seelig, J.; Kemp, J. A.

    1997-08-01

    The accumulation of β -amyloid peptides (Aβ ) into senile plaques is one of the hallmarks of Alzheimer disease. Aggregated Aβ is toxic to cells in culture and this has been considered to be the cause of neurodegeneration that occurs in the Alzheimer disease brain. The discovery of compounds that prevent Aβ toxicity may lead to a better understanding of the processes involved and ultimately to possible therapeutic drugs. Low nanomolar concentrations of Aβ 1-42 and the toxic fragment Aβ 25-35 have been demonstrated to render cells more sensitive to subsequent insults as manifested by an increased sensitivity to formazan crystals following MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction. Formation of the toxic β -sheet conformation by Aβ peptides is increased by negatively charged membranes. Here we demonstrate that phloretin and exifone, dipolar compounds that decrease the effective negative charge of membranes, prevent association of Aβ 1-40 and Aβ 25-35 to negatively charged lipid vesicles and Aβ induced cell toxicity. These results suggest that Aβ toxicity is mediated through a nonspecific physicochemical interaction with cell membranes.

  15. Pharmacological potential of exercise and RAS vasoactive peptides for prevention of diseases.

    PubMed

    Petriz, Bernardo de Assis; de Almeida, Jeeser Alves; Migliolo, Ludovico; Franco, Octavio Luiz

    2013-09-01

    The Renin-Angiotensin-System (RAS) molecular network has been widely studied, especially with attention to angiotensin II, the main effector peptide among RAS. The relation of Ang II to hypertension pathogenesis has led to research being extended to other molecules from the RAS, such as angiotensin III and IV, angiotensin (1-5), and angiotensin (1-9). Moreover, great pharmacologic advances have been made in hypertension treatment by inhibiting renin and angiotensin converting enzymes and blocking the bonding of angiotensin II to its receptor AT1. Thus, RAS molecular signaling and its effect on blood pressure as well as its relationship to renal function and cardiovascular disease are still being investigated. It is a great challenge to fully cover and understand all molecules from the RAS, especially those that interfere with or have vasoactive properties. Some of these targets respond to exercise, stimulating nitric oxide synthesis and endothelial vasodilation. The activation of these specific molecules via exercise is a systematic way of controlling high blood pressure without pharmacological treatment. Angiotensin (1-7) has been focused due to its vasodilation properties and its responses to exercise, improving vascular function. Thus, stimulation of the ACE2/Ang (1-7)/Mas axis has been gaining ground as a prospective clinical means to attenuate cardiovascular diseases such as hypertension by modulating RAS activity. This review focuses on the vasoactive peptides from the RAS, their responses to exercise and possible trends for pharmacological development. In several cases where exercise training is not achievable, cardiovascular drug therapy with vasodilator peptides may possibly be an option.

  16. Whey peptides prevent chronic ultraviolet B radiation-induced skin aging in melanin-possessing male hairless mice.

    PubMed

    Kimura, Yoshiyuki; Sumiyoshi, Maho; Kobayashi, Toshiya

    2014-01-01

    Whey proteins or peptides exhibit various actions, including an antioxidant action, an anticancer action, and a protective action against childhood asthma and atopic syndrome. The effects of orally administered whey peptides (WPs) on chronic ultraviolet B (UVB) radiation-induced cutaneous changes, including changes in cutaneous thickness, elasticity, wrinkle formation, etc., have not been examined. In this study, we studied the preventive effects of WPs on cutaneous aging induced by chronic UVB irradiation in melanin-possessing male hairless mice (HRM). UVB (36-180 mJ/cm(2)) was irradiated to the dorsal area for 17 wk in HRM, and the measurements of cutaneous thickness and elasticity in UVB irradiated mice were performed every week. WPs (200 and 400 mg/kg, twice daily) were administered orally for 17 wk. WPs inhibited the increase in cutaneous thickness, wrinkle formation, and melanin granules and the reduction in cutaneous elasticity associated with photoaging. Furthermore, it has been reported that UVB irradiation-induced skin aging is closely associated with the increase in expression of matrix metalloproteinase (MMP), vascular endothelial growth factor (VEGF), Ki-67-, and 8-hydroxy-2'-deoxyguanosine (8-OHdG)-positive cells. WPs also prevented increases in the expression of MMP-2 and pro-MMP-9, VEGF, and Ki-67- and 8-OHdG-positive cells induced by chronic UVB irradiation. It was found that WPs prevent type IV collagen degradation, angiogenesis, proliferation, and DNA damage caused by UVB irradiation. Overall, these results demonstrate the considerable benefit of WPs for protection against solar UV-irradiated skin aging as a supplemental nutrient.

  17. Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunction.

    PubMed

    Choe, Shawn; Bond, Christopher W; Harrington, Daniel A; Stupp, Samuel I; McVary, Kevin T; Podlasek, Carol A

    2017-01-01

    Erectile dysfunction (ED) has high impact on quality of life in prostatectomy, diabetic and aging patients. An underlying mechanism is cavernous nerve (CN) injury, which causes ED in up to 80% of prostatectomy patients. We examine how sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO undergoes anterograde transport to signal to downstream targets. With crush injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO localization changes to the neuronal cell surface, and anterograde transport stops. With SHH treatment SHH is taken up at the injury site and undergoes retrograde transport to PG neurons, allowing SMO transport to occur, and neurons remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal, glial and downstream target signaling, and is significant as a regenerative therapy. Published by Elsevier Inc.

  18. Grape-seed procyanidins prevent the cafeteria-diet-induced decrease of glucagon-like peptide-1 production.

    PubMed

    González-Abuín, Noemi; Martínez-Micaelo, Neus; Blay, Mayte; Ardévol, Anna; Pinent, Montserrat

    2014-02-05

    Grape-seed procyanidin extract (GSPE) has been reported to improve insulin resistance in cafeteria rats. Because glucagon-like peptide-1 (GLP-1) is involved in glucose homeostasis, the preventive effects of GSPE on GLP-1 production, secretion, and elimination were evaluated in a model of diet-induced insulin resistance. Rats were fed a cafeteria diet for 12 weeks, and 25 mg of GSPE/kg of body weight was administered concomitantly. Vehicle-treated cafeteria-fed rats and chow-fed rats were used as controls. The cafeteria diet decreased active GLP-1 plasma levels, which is attributed to a decreased intestinal GLP-1 production, linked to reduced colonic enteroendocrine cell populations. Such effects were prevented by GSPE. In the same context, GSPE avoided the decrease on intestinal dipeptidyl-peptidase 4 (DPP4) activity and modulated the gene expression of GLP-1 and its receptor in the hypothalamus. In conclusion, the preventive treatment with GSPE abrogates the effects of the cafeteria diet on intestinal GLP-1 production and DPP4 activity.

  19. Reinstatement of cocaine place-conditioning prevented by the peptide kappa-opioid receptor antagonist arodyn.

    PubMed

    Carey, A N; Borozny, K; Aldrich, J V; McLaughlin, J P

    2007-08-13

    Stress contributes to the reinstatement of cocaine-seeking behavior in abstinent subjects. Kappa-opioid receptor antagonists attenuate the behavioral effects of stress, potentially providing therapeutic value in treating cocaine abuse. Presently, the peptide arodyn produced long-lasting kappa-opioid receptor antagonism, suppressing kappa-opioid receptor agonist-induced antinociception at least 3 days after intracerebroventricular administration of 0.3 nmol. C57Bl/6J mice demonstrated cocaine-conditioned place preference, extinction over 3 weeks, and a subsequent reinstatement of place preference. Arodyn pretreatment suppressed stress-induced, but not cocaine-exposed, reinstatement of cocaine place preference. These results verify that arodyn and other kappa-opioid receptor antagonists may be useful therapeutics for cocaine abuse.

  20. Nondepleting anti-CD4 monoclonal antibody prevents diabetes and blocks induction of insulin autoantibodies following insulin peptide B:9-23 immunization in the NOD mouse.

    PubMed

    Liu, Edwin; Moriyama, Hiroaki; Paronen, Johanna; Abiru, Norio; Miao, Dongmei; Yu, Liping; Taylor, Robert M; Eisenbarth, George S

    2003-11-01

    Insulin peptide B:9-23 is a major autoantigen in type 1 diabetes that induces insulin autoantibodies and prevents diabetes in the NOD. However, immunization with peptide without adjuvant may be insufficient to reverse disease or induce long-term tolerance. Furthermore, recent experience has demonstrated the potential dangers of disease exacerbation or anaphylaxis with peptide immunotherapy. Combination therapy of B:9-23 with a nondepleting anti-CD4 monoclonal antibody (YTS 177.9) was studied in female NOD mice from 4 through 6 weeks of age. Injections of either B:9-23 in saline, YTS 177.9 antibody, or both peptide and antibody were given to mice. By 52 weeks follow-up, 40% of B:9-23-treated, 100% of YTS177.9-treated, and 70% of B:9-23 and YTS177.9 combination-treated mice remained diabetes-free. IAA, both spontaneous and induced by B:9-23, was almost completely suppressed in mice receiving YTS 177.9. In addition to suppression of IAA expression, anti-B:9-23 peptide antibodies are also suppressed in mice receiving B:9-23 with YTS 177.9, compared to B:9-23 alone. A brief course of the nondepleting anti-CD4 monoclonal antibody (YTS 177.9) in NOD mice confers long-term protection from diabetes and insulitis and profoundly blocks spontaneous and B:9-23 peptide-induced insulin autoantibodies.

  1. Histone deacetylase inhibition prevents the impairing effects of hippocampal gastrin-releasing peptide receptor antagonism on memory consolidation and extinction.

    PubMed

    Petry, Fernanda S; Dornelles, Arethuza S; Lichtenfels, Martina; Valiati, Fernanda E; de Farias, Caroline Brunetto; Schwartsmann, Gilberto; Parent, Marise B; Roesler, Rafael

    2016-07-01

    Hippocampal gastrin-releasing peptide receptors (GRPR) regulate memory formation and extinction, and disturbances in GRPR signaling may contribute to cognitive impairment associated with neurodevelopmental disorders. Histone acetylation is an important epigenetic mechanism that regulates gene expression involved in memory formation, and histone deacetylase inhibitors (HDACis) rescue memory deficits in several models. The present study determined whether inhibiting histone deacetylation would prevent memory impairments produced by GRPR blockade in the hippocampus. Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or the HDACi sodium butyrate (NaB) shortly before inhibitory avoidance (IA) training, followed by an infusion of either SAL or the selective GRPR antagonist RC-3095 immediately after training. In a second experiment, the infusions were administered before and after a retention test trial that served as extinction training. As expected, RC-3095 significantly impaired consolidation and extinction of IA memory. More importantly, pretraining administration of NaB, at a dose that had no effect when given alone, prevented the effects of RC-3095. In addition, the combination of NaB and RC-3095 increased hippocampal levels of the brain-derived neurotrophic factor (BDNF). These findings indicate that HDAC inhibition can protect against memory impairment caused by GRPR blockade. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice.

    PubMed

    Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

    2016-02-28

    To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. These results suggest that GLP-1 inhibits hepatic steatosis and

  3. Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice

    PubMed Central

    Yamamoto, Takaya; Nakade, Yukiomi; Yamauchi, Taeko; Kobayashi, Yuji; Ishii, Norimitsu; Ohashi, Tomohiko; Ito, Kiyoaki; Sato, Ken; Fukuzawa, Yoshitaka; Yoneda, Masashi

    2016-01-01

    AIM: To investigate whether a glucagon-like peptide-1 (GLP-1) analogue inhibits nonalcoholic steatohepatitis (NASH), which is being increasingly recognized in Asia, in non-obese mice. METHODS: A methionine-choline-deficient diet (MCD) along with exendin-4 (20 μg/kg per day, ip), a GLP-1 analogue, or saline was administered to male db/db mice (non-obese NASH model). Four or eight weeks after commencement of the diet, the mice were sacrificed and their livers were excised. The excised livers were examined by histochemistry for evidence of hepatic steatosis and inflammation. Hepatic triglyceride (TG) and free fatty acid (FFA) content was measured, and the expression of hepatic fat metabolism- and inflammation-related genes was evaluated. Oxidative stress-related parameters and macrophage recruitment were also examined using immunohistochemistry. RESULTS: Four weeks of MCD feeding induced hepatic steatosis and inflammation and increased the hepatic TG and FFA content. The expression of fatty acid transport protein 4 (FATP4), a hepatic FFA influx-related gene; macrophage recruitment; and the level of malondialdehyde (MDA), an oxidative stress marker, were significantly augmented by a 4-wk MCD. The levels of hepatic sterol regulatory element-binding protein-1c (SREBP-1c) mRNA (lipogenesis-related gene) and acyl-coenzyme A oxidase 1 (ACOX1) mRNA (β-oxidation-related gene) had decreased at 4 wk and further decreased at 8 wk. However, the level of microsomal triglyceride transfer protein mRNA (a lipid excretion-related gene) remained unchanged. The administration of exendin-4 significantly attenuated the MCD-induced increase in hepatic steatosis, hepatic TG and FFA content, and FATP4 expression as well as the MCD-induced augmentation of hepatic inflammation, macrophage recruitment, and MDA levels. Additionally, it further decreased the hepatic SREBP-1c level and alleviated the MCD-mediated inhibition of the ACOX1 mRNA level. CONCLUSION: These results suggest that GLP-1

  4. Egg white-derived peptides prevent male reproductive dysfunction induced by mercury in rats.

    PubMed

    Rizzetti, Danize Aparecida; Martinez, Caroline Silveira; Escobar, Alyne Goulart; da Silva, Taiz Martins; Uranga-Ocio, José Antonio; Peçanha, Franck Maciel; Vassallo, Dalton Valentim; Castro, Marta Miguel; Wiggers, Giulia Alessandra

    2017-02-01

    Oxidative stress in known to contribute to the male reproductive dysfunction induced by mercury (Hg). Our study tested the hypothesis that the egg white hydrolysate (EWH), a potent antioxidant in vitro, is able to prevent the effects of prolonged Hg exposure on male reproductive system in rats. For this, rats were treated for 60 days with: a) Untreated - saline solution (i.m.); b) Hydrolysate - EWH (1 g/kg/day, gavage); c) Mercury - HgCl 2 (1st dose 4.6 μg/kg, subsequent doses 0.07 μg/kg/day, i.m.); d) Hydrolysate-Mercury. At the end of the treatment, sperm motility, count and morphological studies were performed; Reactive Oxygen Species (ROS) levels, lipid peroxidation, antioxidant capacity, histological and immunohistochemical assays on testis and epididymis were also carried out. As results, HgCl 2 -treatment decreased sperm number, increased sperm transit time in epididymis and impaired sperm morphology. However, these harmful effects were prevented by EWH. HgCl 2 -treatment also increased ROS levels, lipid peroxidation and antioxidant capacity in testis and epididymis as well as promoted testicular inflammation and histological changes in epididymis. EWH improved histological and immunohistochemical alterations, probably due to its antioxidant property. In conclusion, the EWH could represent a powerful natural alternative to protect the male reproductive system against Hg-induced sperm toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The soybean peptide lunasin promotes apoptosis of mammary epithelial cells via induction of tumor suppressor PTEN: similarities and distinct actions from soy isoflavone genistein

    USDA-ARS?s Scientific Manuscript database

    Breast cancer is the leading cause of cancer deaths in women. Diet and lifestyle are major contributing factors to increased breast cancer risk. While mechanisms underlying dietary protection of mammary tumor formation are increasingly elucidated, there remains a dearth of knowledge on the nature an...

  6. Oral treatment with β-lactoglobulin peptides prevents clinical symptoms in a mouse model for cow's milk allergy.

    PubMed

    Meulenbroek, Laura A P M; van Esch, Betty C A M; Hofman, Gerard A; den Hartog Jager, Constance F; Nauta, Alma J; Willemsen, Linette E M; Bruijnzeel-Koomen, Carla A F M; Garssen, Johan; van Hoffen, Els; Knippels, Léon M J

    2013-11-01

    Prior exposure to partial whey hydrolysates has been shown to reduce the allergic response to whey in mice. This effect was more pronounced in combination with a diet containing non-digestible oligosaccharides (scGOS/lcFOS/pAOS). It is unknown which fractions/epitopes are responsible for this effect. Therefore, the prophylactic ability of synthetic peptides of β-lactoglobulin with/without a scGOS/lcFOS/pAOS-containing diet to reduce the allergic response in a mouse model for cow's milk allergy was investigated. Of 31 peptides, nine peptides were selected based on human T cell data. Mice were pre-treated orally with three peptide mixtures or single peptides for six consecutive days. During this period, they received a control or scGOS/lcFOS/pAOS-containing diet. Subsequently, mice were orally sensitized to whey and received an intradermal and oral challenge. After sacrifice, serum and mesenteric lymph nodes (MLN) were collected for further analysis. Prior exposure to peptide mixtures 1 and 3 significantly reduced the acute allergic skin response to whey. Mixture 2 showed no effect. An additive effect of the scGOS/lcFOS/pAOS-containing diet was only observed for mixture 1. Of the peptides in mixture 1, one peptide (LLDAQSAPLRVYVEELKP) showed the strongest effect on the acute allergic skin response. This peptide also tended to decrease whey-specific antibody levels and to increase the percentages of CD11b+CD103+ dendritic cells and CD25+Foxp3+ T cells in the MLN. Prior exposure to specific peptides of β-lactoglobulin reduces the allergic response to whey, which may involve regulatory dendritic and T cells. Combining peptides with a sGOS/lcFOS/pAOS-containing diet enhances this effect. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Mycobacterial heat shock protein 65 (mbHSP65)-induced atherosclerosis: Preventive oral tolerization and definition of atheroprotective and atherogenic mbHSP65 peptides.

    PubMed

    Grundtman, Cecilia; Jakic, Bojana; Buszko, Maja; Onestingel, Elisabeth; Almanzar, Giovanni; Demetz, Egon; Dietrich, Hermann; Cappellano, Giuseppe; Wick, Georg

    2015-09-01

    The aim of this study was to identify atherogenic and atheroprotective peptides of bacterial HSP60 [taking mycobacterial HSP65 (mbHSP65) as a potent paradigmatic representative] that could be used as candidates for an orally applied tolerizing vaccine against atherosclerosis. ApoE(-/-) mice were immunized with mbHSP65 protein or peptides, given mbHSP65 orally and then kept either on chow or high cholesterol diet. Atherosclerosis was assessed by en face and immunohistological analysis. Anti-HSP autoantibodies were detected by ELISA. The number and in vitro suppressive function of splenic and lymph node regulatory T cells (Tregs) were analyzed by flow cytometry. Specific T cell reactivity against mbHSP65 protein or peptides was assessed by proliferation assay. Decreased lesion size was accompanied by (a) increased splenic Treg numbers; (b) increased interleukin (IL)-10 mRNA levels in the aorta; (c) increased levels of anti-mbHSP65 and anti-mouse HSP60 antibodies pointing to pro-eukaryotic HSP60 humoral crossreaction, not curtailed by oral tolerization; (d) most importantly, we identified and functionally characterized novel atherogenic and atheroprotective mbHSP65 epitopes. Atheroprotective mbHSP65 peptides may be considered as potential candidates for the development of a tolerizing vaccine to prevent and treat atherosclerosis, while keeping protective immunity to non-atherogenic domains of mbHSP65 intact. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed Blood

    PubMed Central

    De Rose, Robert; Fernandez, Caroline S.; Smith, Miranda Z.; Batten, C. Jane; Alcântara, Sheilajen; Peut, Vivienne; Rollman, Erik; Loh, Liyen; Mason, Rosemarie D.; Wilson, Kim; Law, Matthew G.; Handley, Amanda J.; Kent, Stephen J.

    2008-01-01

    Effective immunotherapies for HIV are needed. Drug therapies are life-long with significant toxicities. Dendritic-cell based immunotherapy approaches are promising but impractical for widespread use. A simple immunotherapy, reinfusing fresh autologous blood cells exposed to overlapping SIV peptides for 1 hour ex vivo, was assessed for the control of SIVmac251 replication in 36 pigtail macaques. An initial set of four immunizations was administered under antiretroviral cover and a booster set of three immunizations administered 6 months later. Vaccinated animals were randomized to receive Gag peptides alone or peptides spanning all nine SIV proteins. High-level, SIV-specific CD4 and CD8 T-cell immunity was induced following immunization, both during antiretroviral cover and without. Virus levels were durably ∼10-fold lower for 1 year in immunized animals compared to controls, and a significant delay in AIDS-related mortality resulted. Broader immunity resulted following immunizations with peptides spanning all nine SIV proteins, but the responses to Gag were weaker in comparison to animals only immunized with Gag. No difference in viral outcome occurred in animals immunized with all SIV proteins compared to animals immunized against Gag alone. Peptide-pulsed blood cells are an immunogenic and effective immunotherapy in SIV-infected macaques. Our results suggest Gag alone is an effective antigen for T-cell immunotherapy. Fresh blood cells pulsed with overlapping Gag peptides is proceeding into trials in HIV-infected humans. PMID:18451982

  9. αB-crystallin, a small heat-shock protein, prevents the amyloid fibril growth of an amyloid β-peptide and β2-microglobulin

    PubMed Central

    2005-01-01

    αB-crystallin, a small heat-shock protein, exhibits molecular chaperone activity. We have studied the effect of αB-crystallin on the fibril growth of the Aβ (amyloid β)-peptides Aβ-(1–40) and Aβ-(1–42). αB-crystallin, but not BSA or hen egg-white lysozyme, prevented the fibril growth of Aβ-(1–40), as revealed by thioflavin T binding, total internal reflection fluorescence microscopy and CD spectroscopy. Comparison of the activity of some mutants and chimaeric α-crystallins in preventing Aβ-(1–40) fibril growth with their previously reported chaperone ability in preventing dithiothreitol-induced aggregation of insulin suggests that there might be both common and distinct sites of interaction on α-crystallin involved in the prevention of amorphous aggregation of insulin and fibril growth of Aβ-(1–40). αB-crystallin also prevents the spontaneous fibril formation (without externally added seeds) of Aβ-(1–42), as well as the fibril growth of Aβ-(1–40) when seeded with the Aβ-(1–42) fibril seed. Sedimentation velocity measurements show that αB-crystallin does not form a stable complex with Aβ-(1–40). The mechanism by which it prevents the fibril growth differs from the known mechanism by which it prevents the amorphous aggregation of proteins. αB-crystallin binds to the amyloid fibrils of Aβ-(1–40), indicating that the preferential interaction of the chaperone with the fibril nucleus, which inhibits nucleation-dependent polymerization of amyloid fibrils, is the mechanism that is predominantly involved. We found that αB-crystallin prevents the fibril growth of β2-microglobulin under acidic conditions. It also retards the depolymerization of β2-microglobulin fibrils, indicating that it can interact with the fibrils. Our study sheds light on the role of small heat-shock proteins in protein conformational diseases, particularly in Alzheimer's disease. PMID:16053447

  10. The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1.

    PubMed

    Sosenko, Jay M; Geyer, Susan; Skyler, Jay S; Rafkin, Lisa E; Ismail, Heba M; Libman, Ingrid M; Liu, Yuk-Fun; DiMeglio, Linda A; Evans-Molina, Carmella; Palmer, Jerry P

    2018-05-01

    The extent of influence of BMI and age on C-peptide at the diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body mass index Z-scores (BMIZ) and age on C-peptide measures at and soon after the diagnosis of T1D. Data from Diabetes Prevention Trial-Type 1 (DPT-1) participants <18.0 years at diagnosis was analyzed. Analyses examined associations of C-peptide measures with BMIZ and age in 2 cohorts: oral glucose tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was utilized. Fasting and area under the curve (AUC) C-peptide from OGTTs (n = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age were included as independent variables in regression models (P < .001 for all). BMIZ and age explained 31%-47% of the variance of C-peptide measures. In an example, 2 individuals with identical AUC C-peptide values had an approximate 5-fold difference in values after adjustments for BMIZ and age. The association between fasting glucose and C-peptide decreased markedly when fasting C-peptide values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). C-peptide measures are strongly and independently related to BMIZ and age at and soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial changes in C-peptide values, and impact the association between glycemia and C-peptide. Such adjustments can improve assessments of β-cell impairment at diagnosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Clinical Efficacy of a Specifically Targeted Antimicrobial Peptide Mouth Rinse: Targeted Elimination of Streptococcus mutans and Prevention of Demineralization

    PubMed Central

    Sullivan, R.; Santarpia, P.; Lavender, S.; Gittins, E.; Liu, Z.; Anderson, M.H.; He, J.; Shi, W.; Eckert, R.

    2011-01-01

    Background/Aims Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective ‘targeting region’ comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a ‘killing region’ consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. Methods In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. Results and Conclusions C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic. PMID:21860239

  12. Local oral immunization with synthetic peptides induces a dual mucosal IgG and salivary IgA antibody response and prevents colonization of Streptococcus mutans.

    PubMed Central

    Lehner, T; Haron, J; Bergmeier, L A; Mehlert, A; Beard, R; Dodd, M; Mielnik, B; Moore, S

    1989-01-01

    A small cell surface antigen of Streptococcus mutans was partially sequenced and the amino terminal peptides of 11, 15 and 20 amino acid residues and a dimer of the 15 and 20 residues peptides were synthesized. The synthetic peptides (SP) were used in topical oral immunization of the gingivomucosal epithelium of macaque monkeys. Sequential examination for antibodies over a period of up to 30 weeks revealed that six applications of the linear or cyclized SP11 and a random SP11 induced negligible or very low antibody levels. In contrast, the SP17 (SP15 with added cysteine at each terminus), SP21 (SP20 with one cysteine) and the dimer (SP35) induced significant anti-SP as well as anti-native streptococcal antibodies in the gingival fluid and in saliva. The functional significance of this immune response was examined by studying its effect on oral colonization of S. mutans following feeding of a carbohydrate-rich diet. Whereas control animals, sham-immunized with a random SP of 11 residues, showed increased colonization of the teeth by S. mutans, there was no colonization or a significant reduction in colonization of animals immunized with the cyclized SP17, linear SP21 or dimerized SP35. These experiments suggest that local immunization with SP derived from the sequences of a streptococcal cell surface antigen induce a dual local immune response of gingival IgG and salivary IgA antibodies against the SP and native SA. These antibodies may be involved in preventing colonization of S. mutans, which is the principal agent in the development of dental caries. PMID:2759661

  13. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  14. Pharmacological activation of autophagy favors the clearing of intracellular aggregates of misfolded prion protein peptide to prevent neuronal death.

    PubMed

    Thellung, Stefano; Scoti, Beatrice; Corsaro, Alessandro; Villa, Valentina; Nizzari, Mario; Gagliani, Maria Cristina; Porcile, Carola; Russo, Claudio; Pagano, Aldo; Tacchetti, Carlo; Cortese, Katia; Florio, Tullio

    2018-02-07

    According to the "gain-of-toxicity mechanism", neuronal loss during cerebral proteinopathies is caused by accumulation of aggregation-prone conformers of misfolded cellular proteins, although it is still debated which aggregation state actually corresponds to the neurotoxic entity. Autophagy, originally described as a variant of programmed cell death, is now emerging as a crucial mechanism for cell survival in response to a variety of cell stressors, including nutrient deprivation, damage of cytoplasmic organelles, or accumulation of misfolded proteins. Impairment of autophagic flux in neurons often associates with neurodegeneration during cerebral amyloidosis, suggesting a role in clearing neurons from aggregation-prone misfolded proteins. Thus, autophagy may represent a target for innovative therapies. In this work, we show that alterations of autophagy progression occur in neurons following in vitro exposure to the amyloidogenic and neurotoxic prion protein-derived peptide PrP90-231. We report that the increase of autophagic flux represents a strategy adopted by neurons to survive the intracellular accumulation of misfolded PrP90-231. In particular, PrP90-231 internalization in A1 murine mesencephalic neurons occurs in acidic structures, showing electron microscopy hallmarks of autophagosomes and autophagolysosomes. However, these structures do not undergo resolution and accumulate in cytosol, suggesting that, in the presence of PrP90-231, autophagy is activated but its progression is impaired; the inability to clear PrP90-231 via autophagy induces cytotoxicity, causing impairment of lysosomal integrity and cytosolic diffusion of hydrolytic enzymes. Conversely, the induction of autophagy by pharmacological  blockade of mTOR kinase or trophic factor deprivation restored autophagy resolution, reducing intracellular PrP90-231 accumulation and neuronal death. Taken together, these data indicate that PrP90-231 internalization induces an autophagic defensive response

  15. All-trans retinoic acid stimulates gene expression of the cardioprotective natriuretic peptide system and prevents fibrosis and apoptosis in cardiomyocytes of obese ob/ob mice.

    PubMed

    Manolescu, Daniel-Constantin; Jankowski, Marek; Danalache, Bogdan A; Wang, Donghao; Broderick, Tom L; Chiasson, Jean-Louis; Gutkowska, Jolanta

    2014-10-01

    In hypertensive rodents, retinoic acid (RA) prevents adverse cardiac remodelling and improves myocardial infarction outcome, but its role in obesity-related changes of cardiac tissue are unclear. We hypothesized that all-trans RA (ATRA) treatment will improve the cardioprotective oxytocin-natriuretic peptides (OT-NP) system, preventing apoptosis and collagen accumulation in hearts of ob/ob mice, a mouse model of obesity and insulin resistance. Female 9-week-old B6.V-Lep/J ob/ob mice (n = 16) were divided into 2 groups: 1 group (n = 8) treated with 100 μg of ATRA dissolved in 100 μL of corn oil (vehicle) delivered daily (∼2 μg·g body weight(-1)·day(-1)) by stomach intubation for 16 days, and 1 group (n = 8) that received the vehicle alone. A group of nonobese littermate mice (n = 9) served as controls. Ob/ob mice exhibited obesity, hyperglycaemia, and downregulation of the cardiac OT-NP system, including the mRNA for the transcription factor GATA4, OT receptor and brain NP, and the protein expression for endothelial nitric oxide synthase. Hearts from ob/ob mice also demonstrated increased apoptosis and collagen accumulation. ATRA treatment induced weight loss and decreased adipocytes diameter in the visceral fat, thus reducing visceral obesity, which is associated with a high risk for cardiovascular disease. RA treatment was associated with a reduction in hyperglycemia and a normalization of the OT-NP system's expression in the hearts of ob/ob mice. Furthermore, ATRA treatment prevented apoptosis and collagen accumulation in hearts of ob/ob mice. The present study indicates that ATRA treatment was effective in restoring the cardioprotective OT-NP system and in preventing abnormal cardiac remodelling in the ob/ob mice.

  16. A novel peptide, colivelin, prevents alcohol-induced apoptosis in fetal brain of C57BL/6 mice: signaling pathway investigations

    PubMed Central

    Sari, Youssef; Chiba, Tomohiro; Yamada, Marina; Rebec, George V.; Aiso, Sadakazu

    2009-01-01

    Fetal alcohol exposure is known to induce cell death through apoptosis. We found that colivelin (CLN), a novel peptide with the sequence SALLRSIPAPAGASRLLLLTGEIDLP, prevents this apoptosis. Our initial experiment revealed that CLN enhanced the viability of primary cortical neurons exposed to alcohol. We then used a mouse model of fetal alcohol exposure to identify the intracellular mechanisms underlying these neuroprotective effects. On embryonic day 7 (E7), weight-matched pregnant females were assigned to the following groups: (1) ethanol liquid diet (ALC) 25% (4.49%, v/v) ethanol derived calories; (2) pair-fed control; (3) normal chow; (4) ALC combined with administration (i.p.) of CLN (20 μg/20 g body weight); and (5) pair-fed combined with administration (i.p.) of CLN (20 μg/20 g body weight). On E13, fetal brains were collected and assayed for TUNEL staining, caspase-3 colorimetric assay, ELISA, and MSD electrochemiluminescence. CLN blocked the alcohol-induced decline in brain weight and prevented alcohol-induced: apoptosis, activation of caspase-3 and increases of cytosolic cytochrome c, and decreases of mitochondrial cytochrome c. Analysis of proteins in the upstream signaling pathway revealed that CLN down-regulated the phosphorylation of the c-Jun N-terminal kinase. Moreover, CLN prevented alcohol-induced reduction in phosphorylation of BAD protein. Thus, CLN appears to act directly on upstream signaling proteins to prevent alcohol-induced apoptosis. Further assessment of these proteins and their signaling mechanisms is likely to enhance development of neuroprotective therapies. PMID:19782727

  17. Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor

    PubMed Central

    Wang, Xiaoqin; Xu, Weidong; Mohapatra, Subhra; Kong, Xiaoyuan; Li, Xu; Lockey, Richard F; Mohapatra, Shyam S

    2008-01-01

    Background Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally. Methods Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines. Results SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls. Conclusion These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma. PMID:18279512

  18. Peptide Vaccines for Leishmaniasis.

    PubMed

    De Brito, Rory C F; Cardoso, Jamille M De O; Reis, Levi E S; Vieira, Joao F; Mathias, Fernando A S; Roatt, Bruno M; Aguiar-Soares, Rodrigo Dian D O; Ruiz, Jeronimo C; Resende, Daniela de M; Reis, Alexandre B

    2018-01-01

    Due to an increase in the incidence of leishmaniases worldwide, the development of new strategies such as prophylactic vaccines to prevent infection and decrease the disease have become a high priority. Classic vaccines against leishmaniases were based on live or attenuated parasites or their subunits. Nevertheless, the use of whole parasite or their subunits for vaccine production has numerous disadvantages. Therefore, the use of Leishmania peptides to design more specific vaccines against leishmaniases seems promising. Moreover, peptides have several benefits in comparison with other kinds of antigens, for instance, good stability, absence of potentially damaging materials, antigen low complexity, and low-cost to scale up. By contrast, peptides are poor immunogenic alone, and they need to be delivered correctly. In this context, several approaches described in this review are useful to solve these drawbacks. Approaches, such as, peptides in combination with potent adjuvants, cellular vaccinations, adenovirus, polyepitopes, or DNA vaccines have been used to develop peptide-based vaccines. Recent advancements in peptide vaccine design, chimeric, or polypeptide vaccines and nanovaccines based on particles attached or formulated with antigenic components or peptides have been increasingly employed to drive a specific immune response. In this review, we briefly summarize the old, current, and future stands on peptide-based vaccines, describing the disadvantages and benefits associated with them. We also propose possible approaches to overcome the related weaknesses of synthetic vaccines and suggest future guidelines for their development.

  19. Ligand-regulated peptide aptamers.

    PubMed

    Miller, Russell A

    2009-01-01

    The peptide aptamer approach employs high-throughput selection to identify members of a randomized peptide library displayed from a scaffold protein by virtue of their interaction with a target molecule. Extending this approach, we have developed a peptide aptamer scaffold protein that can impart small-molecule control over the aptamer-target interaction. This ligand-regulated peptide (LiRP) scaffold, consisting of the protein domains FKBP12, FRB, and GST, binds to the cell-permeable small-molecule rapamycin and the binding of this molecule can prevent the interaction of the randomizable linker region connecting FKBP12 with FRB. Here we present a detailed protocol for the creation of a peptide aptamer plasmid library, selection of peptide aptamers using the LiRP scaffold in a yeast two-hybrid system, and the screening of those peptide aptamers for a ligand-regulated interaction.

  20. Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway.

    PubMed

    Canas, Paula M; Porciúncula, Lisiane O; Cunha, Geanne M A; Silva, Carla G; Machado, Nuno J; Oliveira, Jorge M A; Oliveira, Catarina R; Cunha, Rodrigo A

    2009-11-25

    Alzheimer's disease (AD) is characterized by memory impairment, neurochemically by accumulation of beta-amyloid peptide (namely Abeta(1-42)) and morphologically by an initial loss of nerve terminals. Caffeine consumption prevents memory dysfunction in different models, which is mimicked by antagonists of adenosine A(2A) receptors (A(2A)Rs), which are located in synapses. Thus, we now tested whether A(2A)R blockade prevents the early Abeta(1-42)-induced synaptotoxicity and memory dysfunction and what are the underlying signaling pathways. The intracerebral administration of soluble Abeta(1-42) (2 nmol) in rats or mice caused, 2 weeks later, memory impairment (decreased performance in the Y-maze and object recognition tests) and a loss of nerve terminal markers (synaptophysin, SNAP-25) without overt neuronal loss, astrogliosis, or microgliosis. These were prevented by pharmacological blockade [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261); 0.05 mg . kg(-1) . d(-1), i.p.; for 15 d] in rats, and genetic inactivation of A(2A)Rs in mice. Moreover, these were synaptic events since purified nerve terminals acutely exposed to Abeta(1-42) (500 nm) displayed mitochondrial dysfunction, which was prevented by A(2A)R blockade. SCH58261 (50 nm) also prevented the initial synaptotoxicity (loss of MAP-2, synaptophysin, and SNAP-25 immunoreactivity) and subsequent loss of viability of cultured hippocampal neurons exposed to Abeta(1-42) (500 nm). This A(2A)R-mediated control of neurotoxicity involved the control of Abeta(1-42)-induced p38 phosphorylation and was independent from cAMP/PKA (protein kinase A) pathway. Together, these results show that A(2A)Rs play a crucial role in the development of Abeta-induced synaptotoxicity leading to memory dysfunction through a p38 MAPK (mitogen-activated protein kinase)-dependent pathway and provide a molecular basis for the benefits of caffeine consumption in AD.

  1. Flunarizine Prevents Hepatitis C Virus Membrane Fusion in a Genotype-dependent Manner by Targeting the Potential Fusion Peptide within E1

    PubMed Central

    Perin, Paula M.; Haid, Sibylle; Brown, Richard J. P.; Doerrbecker, Juliane; Schulze, Kai; Zeilinger, Carsten; von Schaewen, Markus; Heller, Brigitte; Vercauteren, Koen; Luxenburger, Eva; Baktash, Yasmine M.; Vondran, Florian W. R.; Speerstra, Sietkse; Awadh, Abdullah; Mukhtarov, Furkat; Schang, Luis M; Kirschning, Andreas; Müller, Rolf; Guzman, Carlos A.; Kaderali, Lars; Randall, Glenn; Meuleman, Philip; Ploss, Alexander; Pietschmann, Thomas

    2015-01-01

    To explore mechanisms of hepatitis C virus (HCV) replication we screened a compound library including licensed drugs. Flunarizine, a diphenylmethylpiperazine used to treat migraine, inhibited HCV cell entry in vitro and in vivo in a genotype-dependent fashion. Analysis of mosaic viruses between susceptible and resistant strains revealed that E1 and E2 glycoproteins confer susceptibility to flunarizine. Time of addition experiments and single particle tracking of HCV demonstrated that flunarizine specifically prevents membrane fusion. Related phenothiazines and pimozide also inhibited HCV infection and preferentially targeted HCV genotype 2 viruses. However, phenothiazines and pimozide exhibited improved genotype coverage including the difficult to treat genotype 3. Flunarizine-resistant HCV carried mutations within the alleged fusion peptide and displayed cross-resistance to these compounds, indicating that these drugs have a common mode of action. Conclusion: These observations reveal novel details about HCV membrane fusion. Moreover, flunarizine and related compounds represent first-in-class HCV fusion inhibitors that merit consideration for repurposing as cost-effective component of HCV combination therapies. PMID:26248546

  2. A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses.

    PubMed

    Shekhar, Anantha; Johnson, Philip L; Fitz, Stephanie D; Nakazato, Atsuro; Chaki, Shigeyuki; Steckler, Thomas; Schmidt, Mark

    2011-04-01

    Corticotropin releasing factor (CRF) is implicated in a variety of stress-related disorders such as depression and anxiety, and blocking CRF receptors is a putative strategy for treating such disorders. Using a well-studied animal model of panic, we tested the efficacy of JNJ19567470/CRA5626, a selective, non-peptidergic CRF type 1 receptor (CRF1) antagonist (3, 10 and 40 mg/kg intraperitoneal injection), in preventing the sodium lactate (NaLac)-induced panic-like behavioural and cardiovascular responses. Adult male rats with chronic reduction of GABA levels (by inhibition of GABA synthesis with l-allyglycine, a glutamic acid decarboxylase inhibitor) in the dorsomedial/perifornical hypothalamus are highly anxious and exhibit physiological and behavioural responses to intravenous NaLac infusions similar to patients with panic disorder. These 'panic-prone' rats pre-treated with vehicle injections displayed NaLac-induced increases in autonomic responses (i.e. tachycardia and hypertensive responses), anxiety-like behaviour in the social interaction test, and flight-like increases in locomotor activity. However, systemically injecting such panic-prone rats with the highest dose of CRF1 receptor antagonist prior to NaLac infusions blocked all NaLac-induced behaviour and cardiovascular responses. These data suggest that selective CRF1 receptor antagonists could be a novel target for developing anti-panic drugs that are as effective as benzodiazepines in acute treatment of a panic attack without the deleterious side-effects (e.g. sedation and cognitive impairment) associated with benzodiazepines.

  3. Prevention

    Treesearch

    Barbara Illman; Gary Man

    2010-01-01

    Prevention is considered the most cost-effective element of the Forest Service Invasive Species Strategy (USDA Forest Service 2004). What makes prevention difficult is the desire to maximize free trade and the resulting benefits to society while, at the same time, protecting natural resources. The role of science is to first identify which commodities pose an...

  4. A Peptide Filtering Relation Quantifies MHC Class I Peptide Optimization

    PubMed Central

    Goldstein, Leonard D.; Howarth, Mark; Cardelli, Luca; Emmott, Stephen; Elliott, Tim; Werner, Joern M.

    2011-01-01

    Major Histocompatibility Complex (MHC) class I molecules enable cytotoxic T lymphocytes to destroy virus-infected or cancerous cells, thereby preventing disease progression. MHC class I molecules provide a snapshot of the contents of a cell by binding to protein fragments arising from intracellular protein turnover and presenting these fragments at the cell surface. Competing fragments (peptides) are selected for cell-surface presentation on the basis of their ability to form a stable complex with MHC class I, by a process known as peptide optimization. A better understanding of the optimization process is important for our understanding of immunodominance, the predominance of some T lymphocyte specificities over others, which can determine the efficacy of an immune response, the danger of immune evasion, and the success of vaccination strategies. In this paper we present a dynamical systems model of peptide optimization by MHC class I. We incorporate the chaperone molecule tapasin, which has been shown to enhance peptide optimization to different extents for different MHC class I alleles. Using a combination of published and novel experimental data to parameterize the model, we arrive at a relation of peptide filtering, which quantifies peptide optimization as a function of peptide supply and peptide unbinding rates. From this relation, we find that tapasin enhances peptide unbinding to improve peptide optimization without significantly delaying the transit of MHC to the cell surface, and differences in peptide optimization across MHC class I alleles can be explained by allele-specific differences in peptide binding. Importantly, our filtering relation may be used to dynamically predict the cell surface abundance of any number of competing peptides by MHC class I alleles, providing a quantitative basis to investigate viral infection or disease at the cellular level. We exemplify this by simulating optimization of the distribution of peptides derived from Human

  5. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway.

    PubMed

    Chen, H L; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C C; Chen, C M

    2016-12-12

    formation of fatty liver by activating JAK2 signal transduction through the JAK2/STAT3 and JAK2/AMPK pathways in the high-fructose-induced fatty liver animal model. Therefore, kefir peptides may have the potential for clinical application for the prevention or treatment of clinical metabolic syndrome.

  6. Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway

    PubMed Central

    Chen, H L; Tsai, T C; Tsai, Y C; Liao, J W; Yen, C C; Chen, C M

    2016-01-01

    , inflammatory reaction and the formation of fatty liver by activating JAK2 signal transduction through the JAK2/STAT3 and JAK2/AMPK pathways in the high-fructose-induced fatty liver animal model. Therefore, kefir peptides may have the potential for clinical application for the prevention or treatment of clinical metabolic syndrome. PMID:27941940

  7. Sardine protein diet increases plasma glucagon-like peptide-1 levels and prevents tissue oxidative stress in rats fed a high-fructose diet.

    PubMed

    Madani, Zohra; Sener, Abdullah; Malaisse, Willy J; Dalila, Ait Yahia

    2015-11-01

    The current study investigated whether sardine protein mitigates the adverse effects of fructose on plasma glucagon‑like peptide-1 (GLP-1) and oxidative stress in rats. Rats were fed casein (C) or sardine protein (S) with or without high‑fructose (HF) for 2 months. Plasma glucose, insulin, GLP‑1, lipid and protein oxidation and antioxidant enzymes were assayed. HF rats developed obesity, hyperglycemia, hyperinsulinemia, insulin resistance and oxidative stress despite reduced energy and food intakes. High plasma creatinine and uric acid levels, in addition to albuminuria were observed in the HF groups. The S‑HF diet reduced plasma glucose, insulin, creatinine, uric acid and homeostasis model assessment‑insulin resistance index levels, however increased GLP‑1 levels compared with the C‑HF diet. Hydroperoxides were reduced in the liver, kidney, heart and muscle of S‑HF fed rats compared with C‑HF fed rats. A reduction in liver, kidney and heart carbonyls was observed in S‑HF fed rats compared with C‑HF fed rats. Reduced levels of nitric oxide (NO) were detected in the liver, kidney and heart of the S‑HF fed rats compared with C‑HF fed rats. The S diet compared with the C diet reduced levels of liver hydroperoxides, heart carbonyls and kidney NO. The S‑HF diet compared with the C‑HF diet increased the levels of liver and kidney superoxide dismutase, liver and muscle catalase, liver, heart and muscle glutathione peroxidase and liver ascorbic acid. The S diet prevented and reversed insulin resistance and oxidative stress, and may have benefits in patients with metabolic syndrome.

  8. Self-assembling peptide matrix for the prevention of esophageal stricture after endoscopic resection: a randomized controlled trial in a porcine model.

    PubMed

    Barret, M; Bordaçahar, B; Beuvon, F; Terris, B; Camus, M; Coriat, R; Chaussade, S; Batteux, F; Prat, F

    2017-05-01

    Esophageal stricture formation after extensive endoscopic resection remains a major limitation of endoscopic therapy for early esophageal neoplasia. This study assessed a recently developed self-assembling peptide (SAP) matrix as a wound dressing after endoscopic resection for the prevention of esophageal stricture. Ten pigs were randomly assigned to the SAP or the control group after undergoing a 5-cm-long circumferential endoscopic submucosal dissection of the lower esophagus. Esophageal diameter on endoscopy and esophagogram, weight variation, and histological measurements of fibrosis, granulation tissue, and neoepithelium were assessed in each animal. The rate of esophageal stricture at day 14 was 40% in the SAP-treated group versus 100% in the control group (P = 0.2). Median interquartile range (IQR) esophageal diameter at day 14 was 8 mm (2.5-9) in the SAP-treated group versus 4 mm (3-4) in the control group (P = 0.13). The median (IQR) stricture indexes on esophagograms at day 14 were 0.32 (0.14-0.48) and 0.26 (0.14-0.33) in the SAP-treated and control groups, respectively (P = 0.42). Median (IQR) weight variation during the study was +0.2 (-7.4; +1.8) and -3.8 (-5.4; +0.6) in the SAP-treated and control groups, respectively (P = 0.9). Fibrosis, granulation tissue, and neoepithelium were not significantly different between the groups. The application of SAP matrix on esophageal wounds after a circumferential endoscopic submucosal dissection delayed the onset of esophageal stricture in a porcine model. © International Society for Diseases of the Esophagus 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum

    PubMed Central

    Mukherjee, Pallavi; Hough, Greg; Chattopadhyay, Arnab; Navab, Mohamad; Fogelman, Hannah R.; Meriwether, David; Williams, Kevin; Bensinger, Steven; Moller, Travis; Faull, Kym F.; Lusis, Aldons J.; Iruela-Arispe, M. Luisa; Bostrom, Kristina I.; Tontonoz, Peter; Reddy, Srinivasa T.; Fogelman, Alan M.

    2017-01-01

    Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-β in jejunum as determined by quantitative RT-PCR (RT-qPCR), immunohistochemistry (IHC), and ELISA (all P < 0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR (P < 0.0001), IHC (P = 0.0019), and ELISA (P < 0.0001), resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS (P < 0.0001). Adding ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0.06% by weight of diet substantially ameliorated these changes. Adding either ezetimibe or Tg6F to WD also ameliorated WD-induced changes in plasma lipids, serum amyloid A, and HDL cholesterol. Adding the same doses of ezetimibe and Tg6F together to WD (combined formulation) was generally more efficacious compared with adding either agent alone. Surprisingly, adding ezetimibe during the preparation of Tg6F, but before addition to WD, was more effective than the combined formulation for all parameters measured in jejunum (P = 0.0329 to P < 0.0001). We conclude the following: i) WD induces IFN-β, CH25H, and 25-OHC in jejunum; and ii) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-β, CH25H, and 25-OHC. PMID:28592401

  10. Transgenic tomatoes expressing the 6F peptide and ezetimibe prevent diet-induced increases of IFN-β and cholesterol 25-hydroxylase in jejunum.

    PubMed

    Mukherjee, Pallavi; Hough, Greg; Chattopadhyay, Arnab; Navab, Mohamad; Fogelman, Hannah R; Meriwether, David; Williams, Kevin; Bensinger, Steven; Moller, Travis; Faull, Kym F; Lusis, Aldons J; Iruela-Arispe, M Luisa; Bostrom, Kristina I; Tontonoz, Peter; Reddy, Srinivasa T; Fogelman, Alan M

    2017-08-01

    Feeding LDL receptor (LDLR)-null mice a Western diet (WD) increased the expression of IFN-β in jejunum as determined by quantitative RT-PCR (RT-qPCR), immunohistochemistry (IHC), and ELISA (all P < 0.0001). WD also increased the expression of cholesterol 25-hydroxylase (CH25H) as measured by RT-qPCR ( P < 0.0001), IHC ( P = 0.0019), and ELISA ( P < 0.0001), resulting in increased levels of 25-hydroxycholesterol (25-OHC) in jejunum as determined by LC-MS/MS ( P < 0.0001). Adding ezetimibe at 10 mg/kg/day or adding a concentrate of transgenic tomatoes expressing the 6F peptide (Tg6F) at 0.06% by weight of diet substantially ameliorated these changes. Adding either ezetimibe or Tg6F to WD also ameliorated WD-induced changes in plasma lipids, serum amyloid A, and HDL cholesterol. Adding the same doses of ezetimibe and Tg6F together to WD (combined formulation) was generally more efficacious compared with adding either agent alone. Surprisingly, adding ezetimibe during the preparation of Tg6F, but before addition to WD, was more effective than the combined formulation for all parameters measured in jejunum ( P = 0.0329 to P < 0.0001). We conclude the following: i ) WD induces IFN-β, CH25H, and 25-OHC in jejunum; and ii ) Tg6F and ezetimibe partially ameliorate WD-induced inflammation by preventing WD-induced increases in IFN-β, CH25H, and 25-OHC. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  11. Biodiscovery of aluminum binding peptides

    NASA Astrophysics Data System (ADS)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Hurley, Margaret M.; Stratis-Cullum, Dimitra

    2013-05-01

    Cell surface peptide display systems are large and diverse libraries of peptides (7-15 amino acids) which are presented by a display scaffold hosted by a phage (virus), bacteria, or yeast cell. This allows the selfsustaining peptide libraries to be rapidly screened for high affinity binders to a given target of interest, and those binders quickly identified. Peptide display systems have traditionally been utilized in conjunction with organic-based targets, such as protein toxins or carbon nanotubes. However, this technology has been expanded for use with inorganic targets, such as metals, for biofabrication, hybrid material assembly and corrosion prevention. While most current peptide display systems employ viruses to host the display scaffold, we have recently shown that a bacterial host, Escherichia coli, displaying peptides in the ubiquitous, membrane protein scaffold eCPX can also provide specific peptide binders to an organic target. We have, for the first time, extended the use of this bacterial peptide display system for the biodiscovery of aluminum binding 15mer peptides. We will present the process of biopanning with macroscopic inorganic targets, binder enrichment, and binder isolation and discovery.

  12. The central repeat domain 1 of Kaposi's sarcoma-associated herpesvirus (KSHV) latency associated-nuclear antigen 1 (LANA1) prevents cis MHC class I peptide presentation

    SciTech Connect

    Kwun, Hyun Jin; Ramos da Silva, Suzane; Department of Pathology, Botucatu School of Medicine at Sao Paulo State University, Sao Paulo

    KSHV LANA1, a latent protein expressed during chronic infection to maintain a viral genome, inhibits major histocompatibility complex class I (MHC I) peptide presentation in cis as a means of immune evasion. Through deletional cloning, we localized this function to the LANA1 central repeat 1 (CR1) subregion. Other CR subregions retard LANA1 translation and proteasomal processing but do not markedly inhibit LANA1 peptide processing by MHC I. Inhibition of proteasomal processing ablates LANA1 peptide presentation. Direct expression of LANA1 within the endoplasmic reticulum (ER) overcomes CR1 inhibition suggesting that CR1 acts prior to translocation of cytoplasmic peptides into the ER.more » By physically separating CR1 from other subdomains, we show that LANA1 evades MHC I peptide processing by a mechanism distinct from other herpesviruses including Epstein-Barr virus (EBV). Although LANA1 and EBV EBNA1 are functionally similar, they appear to use different mechanisms to evade host cytotoxic T lymphocyte surveillance.« less

  13. Peptide identification

    DOEpatents

    Jarman, Kristin H [Richland, WA; Cannon, William R [Richland, WA; Jarman, Kenneth D [Richland, WA; Heredia-Langner, Alejandro [Richland, WA

    2011-07-12

    Peptides are identified from a list of candidates using collision-induced dissociation tandem mass spectrometry data. A probabilistic model for the occurrence of spectral peaks corresponding to frequently observed partial peptide fragment ions is applied. As part of the identification procedure, a probability score is produced that indicates the likelihood of any given candidate being the correct match. The statistical significance of the score is known without necessarily having reference to the actual identity of the peptide. In one form of the invention, a genetic algorithm is applied to candidate peptides using an objective function that takes into account the number of shifted peaks appearing in the candidate spectrum relative to the test spectrum.

  14. Maize Bioactive Peptides against Cancer

    NASA Astrophysics Data System (ADS)

    Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

    2017-06-01

    Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

  15. Physiological role of short peptides in nutrition.

    PubMed

    Tutel'yan, V A; Khavinson, V Kh; Malinin, V V

    2003-01-01

    Here we review new data about the physiological role of short peptides and their use as biologically active food additives (parapharmaceutics). Some approaches to the development of peptide preparations for peroral administration are considered and the mechanisms of nonspecific and tissue-specific effects produced by peroral peptide parapharmaceutics are discussed. Particular attention is given to biological properties of short peptides synthesized at the St. Petersburg Institute of Bioregulation and Gerontology. These peptides hold much promise for the synthesis of parapharmaceutics increasing organism's resistance to extreme factors and preventing accelerated aging and age-related diseases.

  16. Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

    SciTech Connect

    Acar, Handan; Samaeekia, Ravand; Schnorenberg, Mathew R.

    Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are twomore » major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.« less

  17. Alzheimer's Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies-Gains from AIBL and DIAN Cohort Studies.

    PubMed

    Martins, Ralph N; Villemagne, Victor; Sohrabi, Hamid R; Chatterjee, Pratishtha; Shah, Tejal M; Verdile, Giuseppe; Fraser, Paul; Taddei, Kevin; Gupta, Veer B; Rainey-Smith, Stephanie R; Hone, Eugene; Pedrini, Steve; Lim, Wei Ling; Martins, Ian; Frost, Shaun; Gupta, Sunil; O'Bryant, Sid; Rembach, Alan; Ames, David; Ellis, Kathryn; Fuller, Stephanie J; Brown, Belinda; Gardener, Samantha L; Fernando, Binosha; Bharadwaj, Prashant; Burnham, Samantha; Laws, Simon M; Barron, Anna M; Goozee, Kathryn; Wahjoepramono, Eka J; Asih, Prita R; Doecke, James D; Salvado, Olivier; Bush, Ashley I; Rowe, Christopher C; Gandy, Samuel E; Masters, Colin L

    2018-01-01

    Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aβ peptide in Alzheimer's disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ.

  18. Alzheimer’s Disease: A Journey from Amyloid Peptides and Oxidative Stress, to Biomarker Technologies and Disease Prevention Strategies—Gains from AIBL and DIAN Cohort Studies

    PubMed Central

    Martins, Ralph N.; Villemagne, Victor; Sohrabi, Hamid R.; Chatterjee, Pratishtha; Shah, Tejal M.; Verdile, Giuseppe; Fraser, Paul; Taddei, Kevin; Gupta, Veer B.; Rainey-Smith, Stephanie R.; Hone, Eugene; Pedrini, Steve; Lim, Wei Ling; Martins, Ian; Frost, Shaun; Gupta, Sunil; O’Bryant, Sid; Rembach, Alan; Ames, David; Ellis, Kathryn; Fuller, Stephanie J.; Brown, Belinda; Gardener, Samantha L.; Fernando, Binosha; Bharadwaj, Prashant; Burnham, Samantha; Laws, Simon M.; Barron, Anna M.; Goozee, Kathryn; Wahjoepramono, Eka J.; Asih, Prita R.; Doecke, James D.; Salvado, Olivier; Bush, Ashley I.; Rowe, Christopher C.; Gandy, Samuel E.; Masters, Colin L.

    2018-01-01

    Worldwide there are over 46 million people living with dementia, and this number is expected to double every 20 years reaching about 131 million by 2050. The cost to the community and government health systems, as well as the stress on families and carers is incalculable. Over three decades of research into this disease have been undertaken by several research groups in Australia, including work by our original research group in Western Australia which was involved in the discovery and sequencing of the amyloid-β peptide (also known as Aβ or A4 peptide) extracted from cerebral amyloid plaques. This review discusses the journey from the discovery of the Aβ peptide in Alzheimer’s disease (AD) brain to the establishment of pre-clinical AD using PET amyloid tracers, a method now serving as the gold standard for developing peripheral diagnostic approaches in the blood and the eye. The latter developments for early diagnosis have been largely achieved through the establishment of the Australian Imaging Biomarker and Lifestyle research group that has followed 1,100 Australians for 11 years. AIBL has also been instrumental in providing insight into the role of the major genetic risk factor apolipoprotein E ɛ4, as well as better understanding the role of lifestyle factors particularly diet, physical activity and sleep to cognitive decline and the accumulation of cerebral Aβ. PMID:29562546

  19. Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation

    PubMed Central

    Souza, Ana Carolina P.; Bocharov, Alexander V.; Baranova, Irina; Vishnyakova, Tatyana; Huang, Yuning G.; Wilkins, Kenneth J.; Hu, Xuzhen; Street, Jonathan M.; Alvarez-Prats, Alejandro; Mullick, Adam E.; Patterson, Amy P.; Remaley, Alan; Eggerman, Thomas L.; Yuen, Peter S.T.; Star, Robert A.

    2016-01-01

    Scavenger receptor CD36 participates in lipid metabolism and inflammatory pathways important for cardiovascular disease and chronic kidney disease (CKD). Few pharmacological agents are available to slow the progression of CKD. However, apolipoprotein AI-mimetic peptide 5A antagonizes CD36 in vitro. To test the efficacy of 5A, and to test the role of CD36 during CKD, we compared wild type to CD36 knockout mice and wild type mice treated with 5A, in a progressive CKD model that resembles human disease. Knockout and 5A-treated wild type mice were protected from CKD progression without changes in blood pressure and had reductions in cardiovascular risk surrogate markers that are associated with CKD. Treatment with 5A did not further protect CD36 knockout mice from CKD progression, implicating CD36 as its main site of action. In a separate model of kidney fibrosis, 5A-treated wild type mice had less macrophage infiltration and interstitial fibrosis. Peptide 5A exerted anti-inflammatory effects in the kidney and decreases renal expression of inflammasome genes. Thus, CD36 is a new therapeutic target for CKD and its associated cardiovascular risk factors. Peptide 5A may be a promising new agent to slow CKD progression. PMID:26994575

  20. Marine Peptides: Bioactivities and Applications

    PubMed Central

    Cheung, Randy Chi Fai; Ng, Tzi Bun; Wong, Jack Ho

    2015-01-01

    Peptides are important bioactive natural products which are present in many marine species. These marine peptides have high potential nutraceutical and medicinal values because of their broad spectra of bioactivities. Their antimicrobial, antiviral, antitumor, antioxidative, cardioprotective (antihypertensive, antiatherosclerotic and anticoagulant), immunomodulatory, analgesic, anxiolytic anti-diabetic, appetite suppressing and neuroprotective activities have attracted the attention of the pharmaceutical industry, which attempts to design them for use in the treatment or prevention of various diseases. Some marine peptides or their derivatives have high commercial values and had reached the pharmaceutical and nutraceutical markets. A large number of them are already in different phases of the clinical and preclinical pipeline. This review highlights the recent research in marine peptides and the trends and prospects for the future, with special emphasis on nutraceutical and pharmaceutical development into marketed products. PMID:26132844

  1. Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

    PubMed

    Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

    2018-06-01

    The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Treatment of both native and deamidated gluten peptides with an endo-peptidase from Aspergillus niger prevents stimulation of gut-derived gluten-reactive T cells from either children or adults with celiac disease.

    PubMed

    Toft-Hansen, Henrik; Rasmussen, Karina S; Staal, Anne; Roggen, Erwin L; Sollid, Ludvig M; Lillevang, Søren T; Barington, Torben; Husby, Steffen

    2014-08-01

    Celiac disease (CD) is characterized by an inappropriate immunological reaction against gluten driven by gluten-specific CD4+ T cells. We screened 25 proteases and tested 10 for their potential to degrade gluten in vitro. Five proteases were further tested for their ability to prevent the proliferative response by a gluten-specific CD4+ T cell clone and seven gluten-reactive T cell lines to protease-digested gluten peptides. A proline-specific endo-peptidase from Aspergillus niger (AnP2) was particularly efficient at diminishing proliferation after stimulation with cleaved antigen, and could completely block the response against both native and deamidated gluten peptides. We found that AnP2 was efficient down to a 1:64 protease:substrate ratio (w:w). When AnP2 was tested in assays using seven gluten-reactive T cell lines from individual CD patients (three adults and four children), the response to gluten was diminished in all cases. Our study indicates a therapeutic benefit of AnP2 to CD patients. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Prevention and management of carcinoid crises in patients with high-risk neuroendocrine tumours undergoing peptide receptor radionuclide therapy (PRRT): Literature review and case series from two Australian tertiary medical institutions.

    PubMed

    Tapia Rico, Gonzalo; Li, Minmin; Pavlakis, Nick; Cehic, Gabrielle; Price, Timothy J

    2018-05-01

    Peptide receptor radionuclide therapy (PRRT) is an important therapeutic option for somatostatin receptor (SSTR) positive metastatic and/or inoperable neuroendocrine tumours (NETs). However, in patients with poorly controlled carcinoid syndrome, it may lead to an acute flare of carcinoid symptoms or even carcinoid crisis. We report seven patients who received PRRT with ( 177 Lu-DOTA 0 , Tyr 3 ) octreotate ( 177 Lu-octreotate-LuTate) across two Australian tertiary medical institutions who developed acute flare of carcinoid symptoms/carcinoid crisis during/after PRRT. Cases were identified as high-risk due to previous history of carcinoid crises, high tumour burden and markedly elevated tumour markers. We propose a protocol to prevent and manage severe carcinoid symptoms in high-risk patients treated with PRRT. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat Periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1β and TNF-α production.

    PubMed

    Wang, Hong-Yan; Lin, Li; Fu, Wei; Yu, Hui-Yuan; Yu, Ning; Tan, Li-Si; Cheng, Jya-Wei; Pan, Ya-Ping

    2017-08-29

    P-113 (AKRHHGYKRKFH-NH2) is a 12-amino-acid histidine-rich peptide derived from histatin 5 that is highly degradable in high salt concentrations and biological fluids such as serum, plasma and saliva. Nal-P-113, a novel antimicrobial peptide whose histidine residues are replaced by the bulky amino acids β-naphthylalanine, causes the antimicrobial peptide to retain its bactericidal activity even in physiological environments. This study evaluated the effect of the novel antimicrobial peptide Nal-P-113 in a rat periodontitis model and the mechanisms of action of Nal-P-113 for suppressing periodontitis. Periodontitis was induced in mandibular first molars in rats receiving a ligature and infected with Porphyromonas gingivalis. Animals were randomly divided into six groups: a, P. gingivalis W83 alone; b, P. gingivalis W83 with 6.25 μg/mL of Nal-P-113; c, P. gingivalis W83 with 25 μg/mL of Nal-P-113; d, P. gingivalis W83 with 100 μg/mL of Nal-P-113; e, P. gingivalis W83 with 400 μg/mL of Nal-P-113; and f, control without P. gingivalis W83 or Nal-P-113. Morphometric analysis was used to evaluate alveolar bone loss. Microbiological assessment of the presence of Porphyromonas gingivalis and total bacteria was performed using absolute quantitative real-time PCR and scanning electron microscopy. Gingival tissue was collected for western blot and immunohistochemical assays of IL-1β and TNF-α levels. Alveolar bone loss was inhibited by 100 μg/mL or 400 μg/mL of Nal-P-113 compared to the control group (P < 0.05). Lower amounts of P. gingivalis and total bacteria were found in groups d and e compared with group a (P < 0.05). A decrease in the levels of IL-1β and TNF-α was detected in group d and group e compared to the control group (P < 0.05). The amount of P. gingivalis was positively correlated with IL-1β and TNF-α expression in periodontal tissue (P < 0.05). Nal-P-113 exhibited protective effects on Porphyromonas gingivalis-induced periodontitis in

  5. Prevention of stress- or nitric oxide donor-induced medication overuse headache by a calcitonin gene-related peptide antibody in rodents.

    PubMed

    Kopruszinski, Caroline Machado; Xie, Jennifer Yanhua; Eyde, Nathan Mackenzie; Remeniuk, Bethany; Walter, Sarah; Stratton, Jennifer; Bigal, Marcelo; Chichorro, Juliana Geremias; Dodick, David; Porreca, Frank

    2017-05-01

    Objective The objective of this study was the determination of the role of calcitonin gene-related peptide (CGRP) in the induction of medication overuse headache (MOH)-related migraine in an injury-free preclinical model. Methods Rats were primed by a 7-day period of exposure to acute migraine therapies including sumatriptan and morphine. After an additional 14-day drug-free period, rats were exposed to putative migraine triggers including bright light stress (BLS) or nitric oxide (NO) donor in the presence or absence of TEV48125, a fully humanized CGRP antibody. Cutaneous allodynia (CA) was used as an outcome measure and CGRP blood and cerebrospinal fluid (CSF) levels were measured. Results BLS and NO donor challenge evoked delayed, long-lasting CA selectively in rats that were previously treated with sumatriptan or morphine. BLS produced a significant increase in CGRP in the plasma, but not CSF, in animals that were previously exposed to sumatriptan compared to saline controls. TEV48125 did not modify baseline tactile thresholds or produce behavioral side effects, but significantly inhibited both BLS- and NO donor-induced CA in animals that were previously primed with sumatriptan or morphine; an isotype control protein that does not bind CGRP had no effect. Interpretation These data suggest that acute migraine medications may promote MOH in susceptible individuals through CGRP-dependent mechanisms and that anti-CGRP antibodies may be a useful clinical strategy for the treatment of MOH.

  6. The antigen-binding fragment of human gamma immunoglobulin prevents amyloid β-peptide folding into β-sheet to form oligomers

    PubMed Central

    Valls-Comamala, Victòria; Guivernau, Biuse; Bonet, Jaume; Puig, Marta; Perálvarez-Marín, Alex; Palomer, Ernest; Fernàndez-Busquets, Xavier; Altafaj, Xavier; Tajes, Marta; Puig-Pijoan, Albert; Vicente, Rubén; Oliva, Baldomero; Muñoz, Francisco J.

    2017-01-01

    The amyloid beta-peptide (Aβ) plays a leading role in Alzheimer's disease (AD) physiopathology. Even though monomeric forms of Aβ are harmless to cells, Aβ can aggregate into β-sheet oligomers and fibrils, which are both neurotoxic. Therefore, one of the main therapeutic approaches to cure or delay AD onset and progression is targeting Aβ aggregation. In the present study, we show that a pool of human gamma immunoglobulins (IgG) protected cortical neurons from the challenge with Aβ oligomers, as assayed by MTT reduction, caspase-3 activation and cytoskeleton integrity. In addition, we report the inhibitory effect of IgG on Aβ aggregation, as shown by Thioflavin T assay, size exclusion chromatography and atomic force microscopy. Similar results were obtained with Palivizumab, a human anti-sincitial virus antibody. In order to dissect the important domains, we cleaved the pool of human IgG with papain to obtain Fab and Fc fragments. Using these cleaved fragments, we functionally identified Fab as the immunoglobulin fragment inhibiting Aβ aggregation, a result that was further confirmed by an in silico structural model. Interestingly, bioinformatic tools show a highly conserved structure able to bind amyloid in the Fab region. Overall, our data strongly support the inhibitory effect of human IgG on Aβ aggregation and its neuroprotective role. PMID:28467807

  7. The macrocyclic peptide natural product CJ-15,208 is orally active and prevents reinstatement of extinguished cocaine-seeking behavior.

    PubMed

    Aldrich, Jane V; Senadheera, Sanjeewa N; Ross, Nicolette C; Ganno, Michelle L; Eans, Shainnel O; McLaughlin, Jay P

    2013-03-22

    The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-d-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.

  8. The Macrocyclic Peptide Natural Product CJ-15,208 is Orally Active and Prevents Reinstatement of Extinguished Cocaine Seeking Behavior1

    PubMed Central

    Aldrich, Jane V.; Senadheera, Sanjeewa N.; Ross, Nicolette C.; Ganno, Michelle L.; Eans, Shainnel O.; McLaughlin, Jay P.

    2013-01-01

    The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood-brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug seeking behavior in abstinent subjects. PMID:23327691

  9. G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention.

    PubMed

    Conrad, Kirk P

    2016-09-01

    Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand-receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. The published literature relating to the topic was searched through January 2016 using PubMed. Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular attributes in preeclampsia, relaxin supplementation is

  10. G-Protein-coupled receptors as potential drug candidates in preeclampsia: targeting the relaxin/insulin-like family peptide receptor 1 for treatment and prevention

    PubMed Central

    Conrad, Kirk P.

    2016-01-01

    BACKGROUND Important roles for G-protein-coupled receptors (GPCRs) have been identified in the maternal physiological adaptations to pregnancy and in the pathogenesis of preeclampsia. On this basis, GPCRs are potential therapeutic targets for preeclampsia. OBJECTIVES AND RATIONALE In this review, vasopressin and apelin are initially considered in this context before the focus on the hormone relaxin and its cognate receptor, the relaxin/insulin-like family peptide receptor 1 (RXFP1). Based on both compelling scientific rationale and a promising safety profile, the relaxin ligand–receptor system is comprehensively evaluated as a potential therapeutic endpoint in preeclampsia. SEARCH METHODS The published literature relating to the topic was searched through January 2016 using PubMed. OUTCOMES Relaxin is a peptide hormone secreted by the corpus luteum; it circulates in the luteal phase and during pregnancy. Activation of RXFP1 is vasodilatory; thus, relaxin supplementation is expected to at least partly restore the fundamental vasodilatory changes of normal pregnancy, thereby alleviating maternal organ hypoperfusion, which is a major pathogenic manifestation of severe preeclampsia. Specifically, by exploiting its pleiotropic hemodynamic attributes in preeclampsia, relaxin administration is predicted to (i) reverse robust arterial myogenic constriction; (ii) blunt systemic and renal vasoconstriction in response to activation of the angiotensin II receptor, type 1; (iii) mollify the action of endogenous vasoconstrictors on uterine spiral arteries with failed remodeling and retained smooth muscle; (iv) increase arterial compliance; (v) enhance insulin-mediated glucose disposal by promoting skeletal muscle vasodilation and (vi) mobilize and activate bone marrow-derived angiogenic progenitor cells, thereby repairing injured endothelium and improving maternal vascularity in organs such as breast, uterus, pancreas, skin and fat. By exploiting its pleiotropic molecular

  11. Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.

    PubMed

    Chevrier, Geneviève; Mitchell, Patricia L; Rioux, Laurie-Eve; Hasan, Fida; Jin, Tianyi; Roblet, Cyril Roland; Doyen, Alain; Pilon, Geneviève; St-Pierre, Philippe; Lavigne, Charles; Bazinet, Laurent; Jacques, Hélène; Gill, Tom; McLeod, Roger S; Marette, André

    2015-07-01

    We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects. We tested whether a salmon peptide fraction (SPF) could improve MetS in mice and explored potential mechanisms of action. ApoB(100) only, LDL receptor knockout male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1 group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We assessed the impact of dietary treatments on glucose tolerance, adipose tissue inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide synthase activity were further studied in vitro with the use of L6 myocytes, FAO hepatocytes, and J774 macrophages. Mice fed HFS+SPF or HFS+SPF+FO diets had lower body weight (protein effect, P = 0.024), feed efficiency (protein effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower concentrations of adipose tissue cytokines and chemokines (protein effect, P ≤ 0.003) compared with HFS and HFS+FO groups. They also had greater glucose tolerance (protein effect, P < 0.001), lower activation of the mammalian target of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1 (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002) than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS activation in vitro. SPF reduces obesity-linked MetS features in LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory properties of SPF were

  12. CD28 homodimer interface mimetic peptide acts as a preventive and therapeutic agent in models of severe bacterial sepsis and gram-negative bacterial peritonitis.

    PubMed

    Ramachandran, Girish; Kaempfer, Raymond; Chung, Chun-Shiang; Shirvan, Anat; Chahin, Abdullah B; Palardy, John E; Parejo, Nicolas A; Chen, Yaping; Whitford, Melissa; Arad, Gila; Hillman, Dalia; Shemesh, Ronen; Blackwelder, William; Ayala, Alfred; Cross, Alan S; Opal, Steven M

    2015-03-15

    Severe gram-negative bacterial infections and sepsis are major causes of morbidity and mortality. Dysregulated, excessive proinflammatory cytokine expression contributes to the pathogenesis of sepsis. A CD28 mimetic peptide (AB103; previously known as p2TA) that attenuates CD28 signaling and T-helper type 1 cytokine responses was tested for its ability to increase survival in models of polymicrobial infection and gram-negative sepsis. Mice received AB103, followed by an injection of Escherichia coli 0111:B4 lipopolysaccharide (LPS); underwent induction E. coli 018:K1 peritonitis induction, followed by treatment with AB103; or underwent cecal ligation and puncture (CLP), followed by treatment with AB103. The effects of AB103 on factors associated with and the lethality of challenge infections were analyzed. AB103 strongly attenuated induction of tumor necrosis factor α and interleukin 6 (IL-6) by LPS in human peripheral blood mononuclear cells. Receipt of AB103 following intraperitoneal injection of LPS resulted in survival among 73% of CD1 mice (11 of 15), compared with 20% of controls (3 of 15). Suboptimal doses of antibiotic alone protected 20% of mice (1 of 5) from E. coli peritonitis, whereas 100% (15 of 15) survived when AB103 was added 4 hours following infection. Survival among mice treated with AB103 12 hours after CLP was 100% (8 of 8), compared with 17% among untreated mice (1 of 6). In addition, receipt of AB103 12 hours after CLP attenuated inflammatory cytokine responses and neutrophil influx into tissues and promoted bacterial clearance. Receipt of AB103 24 hours after CLP still protected 63% of mice (5 of 8). Single-dose AB103 reduces mortality in experimental models of polymicrobial and gram-negative bacterial infection and sepsis, warranting further studies of this agent in clinical trials. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please

  13. Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.

    PubMed

    Binkowski, Brock F; Miller, Russell A; Belshaw, Peter J

    2005-07-01

    We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.

  14. Exendin-4, a glucagon-like peptide-1 receptor agonist prevents mTBI-induced changes in hippocampus gene expression and memory deficits in mice

    PubMed Central

    Tweedie, D.; Rachmany, L.; Rubovitch, V.; Lehrmann, E.; Zhang, Y.; Becker, K.G.; Perez, E.; Miller, J.; Hoffer, B.J.; Greig, N.H.; Pick, C.G.

    2012-01-01

    Traumatic brain injury (TBI) is a global problem reaching near epidemic numbers that manifests clinically with cognitive problems that decades later may result in dementias like Alzheimer’s disease (AD). Presently, little can be done to prevent ensuing neurological dysfunctions by pharmacological means. Recently, it has become apparent that several CNS diseases share common terminal features of neuronal cell death. The effects of exendin-4 (Ex-4), a neuroprotective agent delivered via a subcutaneous micro-osmotic pump, were examined in the setting of mild TBI (mTBI). Utilizing a model of mTBI, where cognitive disturbances occur over time, animals were subjected to four treatments: sham; Ex-4; mTBI and Ex-4/mTBI. mTBI mice displayed deficits in novel object recognition, while Ex-4/mTBI mice performed similar to sham. Hippocampal gene expression, assessed by gene array methods, showed significant differences with little overlap in co-regulated genes between groups. Importantly, changes in gene expression induced by mTBI, including genes associated with AD were largely prevented by Ex-4. These data suggest a strong beneficial action of Ex-4 in managing secondary events induced by a traumatic brain injury. PMID:23059457

  15. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation).

    PubMed

    Hijazi, Ziad; Wallentin, Lars; Siegbahn, Agneta; Andersson, Ulrika; Christersson, Christina; Ezekowitz, Justin; Gersh, Bernard J; Hanna, Michael; Hohnloser, Stefan; Horowitz, John; Huber, Kurt; Hylek, Elaine M; Lopes, Renato D; McMurray, John J V; Granger, Christopher B

    2013-06-04

    This study sought to assess the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels. Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases. In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors. Quartiles of NT-proBNP were: Q1, ≤363 ng/l; Q2, 364 to 713 ng/l; Q3, 714 to 1,250 ng/l; and Q4, >1,250 ng/l. During 1.9 years, the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, an adjusted hazard ratio of 2.35 (95% confidence interval [CI]: 1.62 to 3.40; p < 0.0001). Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, with an adjusted hazard ratio of 2.50 (95% CI: 1.81 to 3.45; p < 0.0001). Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p = 0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p < 0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level. NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). Copyright

  16. Regulatory Peptides in Plants.

    PubMed

    Vanyushin, B F; Ashapkin, V V; Aleksandrushkina, N I

    2017-02-01

    Many different peptides regulating cell differentiation, growth, and development are found in plants. Peptides participate in regulation of plant ontogenesis starting from pollination, pollen tube growth, and the very early stages of embryogenesis, including formation of embryo and endosperm. They direct differentiation of meristematic stem cells, formation of tissues and individual organs, take part in regulation of aging, fruit maturation, and abscission of plant parts associated with apoptosis. Biological activity of peptides is observed at very low concentrations, and it has mainly signal nature and hormonal character. "Mature" peptides appear mainly due to processing of protein precursors with (or without) additional enzymatic modifications. Plant peptides differ in origin, structure, and functional properties. Their specific action is due to binding with respective receptors and interactions with various proteins and other factors. Peptides can also regulate physiological functions by direct peptide-protein interactions. Peptide action is coordinated with the action of known phytohormones (auxins, cytokinins, and others); thus, peptides control phytohormonal signal pathways.

  17. A Cocoa Peptide Protects Caenorhabditis elegans from Oxidative Stress and β-Amyloid Peptide Toxicity

    PubMed Central

    Martorell, Patricia; Bataller, Esther; Llopis, Silvia; Gonzalez, Núria; Álvarez, Beatriz; Montón, Fernando; Ortiz, Pepa; Ramón, Daniel; Genovés, Salvador

    2013-01-01

    Background Cocoa and cocoa-based products contain different compounds with beneficial properties for human health. Polyphenols are the most frequently studied, and display antioxidant properties. Moreover, protein content is a very interesting source of antioxidant bioactive peptides, which can be used therapeutically for the prevention of age-related diseases. Methodology/Principal Findings A bioactive peptide, 13L (DNYDNSAGKWWVT), was obtained from a hydrolyzed cocoa by-product by chromatography. The in vitro inhibition of prolyl endopeptidase (PEP) was used as screening method to select the suitable fraction for peptide identification. Functional analysis of 13L peptide was achieved using the transgenic Caenorhabditis elegans strain CL4176 expressing the human Aβ1–42 peptide as a pre-clinical in vivo model for Alzheimer's disease. Among the peptides isolated, peptide 13L (1 µg/mL) showed the highest antioxidant activity (P≤0.001) in the wild-type strain (N2). Furthermore, 13L produced a significant delay in body paralysis in strain CL4176, especially in the 24–47 h period after Aβ1–42 peptide induction (P≤0.0001). This observation is in accordance with the reduction of Aβ deposits in CL4176 by western blot. Finally, transcriptomic analysis in wild-type nematodes treated with 13L revealed modulation of the proteosomal and synaptic functions as the main metabolic targets of the peptide. Conclusions/Significance These findings suggest that the cocoa 13L peptide has antioxidant activity and may reduce Aβ deposition in a C. elegans model of Alzheimer's disease; and therefore has a putative therapeutic potential for prevention of age-related diseases. Further studies in murine models and humans will be essential to analyze the effectiveness of the 13L peptide in higher animals. PMID:23675471

  18. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

  19. PH dependent adhesive peptides

    DOEpatents

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  20. Bioactive Proteins and Peptides from Soybeans.

    PubMed

    Agyei, Dominic

    2015-01-01

    Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

  1. Peptides and methods against diabetes

    DOEpatents

    Albertini, Richard J.; Falta, Michael T.

    2000-01-01

    This invention relates to methods of preventing or reducing the severity of diabetes. In one embodiment, the method involves administering to the individual a peptide having substantially the sequence of a on-conserved region sequence of a T cell receptor present on the surface of T cells mediating diabetes or a fragment thereof, wherein the peptide or fragment is capable of causing an effect on the immune system to regulate the T cells. In particular, the T cell receptor has the V.beta. regional V.beta.6 or V.beta.14. In another embodiment, the method involves gene therapy. The invention also relates to methods of diagnosing diabetes by determining the presence of diabetes predominant T cell receptors.

  2. Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy.

    PubMed

    Stockburger, Martin; de Teresa, Eduardo; Lamas, Gervasio; Desaga, Martin; Koenig, Carsten; Habedank, Dirk; Cobo, Erik; Navarro, Xavier; Wiegand, Uwe

    2014-01-01

    Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

  3. Cell Penetrating Peptides and Cationic Antibacterial Peptides

    PubMed Central

    Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

    2014-01-01

    Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

  4. [Plant signaling peptides. Cysteine-rich peptides].

    PubMed

    Ostrowski, Maciej; Kowalczyk, Stanisław

    2015-01-01

    Recent bioinformatic and genetic analyses of several model plant genomes have revealed the existence of a highly abundant group of signaling peptides that are defined as cysteine-rich peptides (CRPs). CRPs are usually in size between 50 and 90 amino acid residues, they are positively charged, and they contain 4-16 cysteine residues that are important for the correct conformational folding. Despite the structural differences among CRP classes, members from each class have striking similarities in their molecular properties and function. The present review presents the recent progress in research on signaling peptides from several families including: EPF/EPFL, SP11/SCR, PrsS, RALF, LURE, and some other peptides belonging to CRP group. There is convincing evidence indicating multiple roles for these CRPs as signaling molecules during the plant life cycle, ranging from stomata development and patterning, self-incompatibility, pollen tube growth and guidance, reproductive processes, and nodule formation.

  5. Plant peptide hormone signalling.

    PubMed

    Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

    2015-01-01

    The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

  6. Antimicrobial Peptides in Reptiles

    PubMed Central

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  7. Peptides in melanoma therapy.

    PubMed

    Mocellin, Simone

    2012-01-01

    Peptides derived from tumor associated antigens can be utilized to elicit a therapeutically effective immune response against melanoma in experimental models. However, patient vaccination with peptides - although it is often followed by the induction of melanoma- specific T lymphocytes - is rarely associated with tumor response of clinical relevance. In this review I summarize the principles of peptide design as well as the results so far obtained in the clinical setting while treating cutaneous melanoma by means of this active immunotherapy strategy. I also discuss some immunological and methodological issues that might be helpful for the successful development of peptide-based vaccines.

  8. Insulin C-peptide test

    MedlinePlus

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  9. Peptide bioregulators inhibit apoptosis.

    PubMed

    Khavinson, V K; Kvetnoii, I M

    2000-12-01

    The effects of peptide bioregulators epithalon and vilon on the dynamics of irradiation-induced apoptotic death of spleen lymphocytes in rats indicate that these agents inhibit physiologically programmed cell death. The antiapoptotic effect of vilon was more pronounced, which corroborates the concept on tissue-specific effect of peptide bioregulators.

  10. Cell-permeable, mitochondrial-targeted, peptide antioxidants.

    PubMed

    Szeto, Hazel H

    2006-04-21

    Cellular oxidative injury has been implicated in aging and a wide array of clinical disorders including ischemia-reperfusion injury; neurodegenerative diseases; diabetes; inflammatory diseases such as atherosclerosis, arthritis, and hepatitis; and drug-induced toxicity. However, available antioxidants have not proven to be particularly effective against many of these disorders. A possibility is that some of the antioxidants do not reach the relevant sites of free radical generation, especially if mitochondria are the primary source of reactive oxygen species (ROS). The SS (Szeto-Schiller) peptide antioxidants represent a novel approach with targeted delivery of antioxidants to the inner mitochondrial membrane. The structural motif of these SS peptides centers on alternating aromatic residues and basic amino acids (aromatic-cationic peptides). These SS peptides can scavenge hydrogen peroxide and peroxynitrite and inhibit lipid peroxidation. Their antioxidant action can be attributed to the tyrosine or dimethyltyrosine residue. By reducing mitochondrial ROS, these peptides inhibit mitochondrial permeability transition and cytochrome c release, thus preventing oxidant-induced cell death. Because these peptides concentrate >1000-fold in the inner mitochondrial membrane, they prevent oxidative cell death with EC50 in the nM range. Preclinical studies support their potential use for ischemia-reperfusion injury and neurodegenerative disorders. Although peptides have often been considered to be poor drug candidates, these small peptides have excellent "druggable" properties, making them promising agents for many diseases with unmet needs.

  11. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    PubMed

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  12. Perspective of Use of Antiviral Peptides against Influenza Virus

    PubMed Central

    Skalickova, Sylvie; Heger, Zbynek; Krejcova, Ludmila; Pekarik, Vladimir; Bastl, Karel; Janda, Jozef; Kostolansky, Frantisek; Vareckova, Eva; Zitka, Ondrej; Adam, Vojtech; Kizek, Rene

    2015-01-01

    The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides. PMID:26492266

  13. Role of Host-Defence Peptides in Eye Diseases

    PubMed Central

    Kolar, Satya S.; McDermott, Alison M.

    2013-01-01

    The eye and its associated tissues including the lacrimal system and lids have evolved several defence mechanisms to prevent microbial invasion. Included among this armory are several host-defence peptides. These multifunctional molecules are being studied not only for their endogenous antimicrobial properties but also for their potential therapeutic effects. Here the current knowledge of host-defence peptide expression in the eye will be summarized. The role of these peptides in eye disease will be discussed with the primary focus being on infectious keratitis, inflammatory conditions including dry eye and wound healing. Finally the potential of using host-defence peptides and their mimetics/derivatives for the treatment and prevention of eye diseases is addressed. PMID:21584809

  14. Synthetic peptides that cause F-actin bundling and block actin depolymerization

    DOEpatents

    Sederoff, Heike [Raleigh, NC; Huber, Steven C [Savoy, IL; Larabell, Carolyn A [Berkeley, CA

    2011-10-18

    Synthetic peptides derived from sucrose synthase, and having homology to actin and actin-related proteins, sharing a common motif, useful for causing acting bundling and preventing actin depolymerization. Peptides exhibiting the common motif are described, as well as specific synthetic peptides which caused bundled actin and inhibit actin depolymerization. These peptides can be useful for treating a subject suffering from a disease characterized by cells having neoplastic growth, for anti-cancer therapeutics, delivered to subjects solely, or concomitantly or sequentially with other known cancer therapeutics. These peptides can also be used for stabilizing microfilaments in living cells and inhibiting growth of cells.

  15. A Review of the Latest Advances in Encrypted Bioactive Peptides from Protein-Rich Waste

    PubMed Central

    Lemes, Ailton Cesar; Sala, Luisa; Ores, Joana da Costa; Braga, Anna Rafaela Cavalcante; Egea, Mariana Buranelo; Fernandes, Kátia Flávia

    2016-01-01

    Bioactive peptides are considered the new generation of biologically active regulators that not only prevent the mechanism of oxidation and microbial degradation in foods but also enhanced the treatment of various diseases and disorders, thus increasing quality of life. This review article emphasizes recent advances in bioactive peptide technology, such as: (i) new strategies for transforming bioactive peptides from residual waste into added-value products; (ii) nanotechnology for the encapsulation, protection and release of controlled peptides; and (iii) use of techniques of large-scale recovery and purification of peptides aiming at future applications to pharmaceutical and food industries. PMID:27322241

  16. Inhibition of HIV infection by caerin 1 antimicrobial peptides.

    PubMed

    VanCompernolle, Scott; Smith, Patricia B; Bowie, John H; Tyler, Michael J; Unutmaz, Derya; Rollins-Smith, Louise A

    2015-09-01

    The major mode of transmission of the human immunodeficiency virus (HIV) is by sexual intercourse. In the effort to halt the spread of HIV, one measure that holds great promise is the development of effective microbicides that can prevent transmission. Previously we showed that several amphibian antimicrobial peptides (AMPs) completely inhibit HIV infection of T cells while maintaining good viability of the T cell targets. These peptides also inhibited the transfer of HIV by dendritic cells (DCs) to T cells when added up to 8h after virus exposure. Here we report on the anti-HIV activity of 18 additional structurally related caerin 1 family peptides in comparison with our previous best candidate caerin 1.9. Nine peptides were equally effective or more effective in the inhibition of T cell infection and disruption of the HIV envelope as caerin 1.9. Of those nine peptides, three peptides (caerin 1.2, caerin 1.10, and caerin 1.20) exhibited excellent inhibition of HIV infectivity at low concentrations (12-25μM) and limited toxicity against target T cells and endocervical epithelial cells. There was a direct correlation between the effectiveness of the peptides in disruption of the viral envelope and their capacity to inhibit infection. Thus, several additional caerin 1 family peptides inhibit HIV infection have limited toxicity for vaginal epithelial cells, and would be good candidates for inclusion in microbicide formulations. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Peptide Integrated Optics.

    PubMed

    Handelman, Amir; Lapshina, Nadezda; Apter, Boris; Rosenman, Gil

    2018-02-01

    Bio-nanophotonics is a wide field in which advanced optical materials, biomedicine, fundamental optics, and nanotechnology are combined and result in the development of biomedical optical chips. Silk fibers or synthetic bioabsorbable polymers are the main light-guiding components. In this work, an advanced concept of integrated bio-optics is proposed, which is based on bioinspired peptide optical materials exhibiting wide optical transparency, nonlinear and electrooptical properties, and effective passive and active waveguiding. Developed new technology combining bottom-up controlled deposition of peptide planar wafers of a large area and top-down focus ion beam lithography provides direct fabrication of peptide optical integrated circuits. Finding a deep modification of peptide optical properties by reconformation of biological secondary structure from native phase to β-sheet architecture is followed by the appearance of visible fluorescence and unexpected transition from a native passive optical waveguiding to an active one. Original biocompatibility, switchable regimes of waveguiding, and multifunctional nonlinear optical properties make these new peptide planar optical materials attractive for application in emerging technology of lab-on-biochips, combining biomedical photonic and electronic circuits toward medical diagnosis, light-activated therapy, and health monitoring. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  19. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus.

    PubMed

    Hemmingsen, Bianca; Sonne, David P; Metzendorf, Maria-Inti; Richter, Bernd

    2017-05-10

    The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. We searched the Cochrane Central Register of Controlled Trials; MEDLINE; PubMed; Embase; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform; and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was January 2017. We included randomised controlled trials (RCTs) with a duration of 12 weeks or more comparing DPP-4 inhibitors and GLP-1 analogues with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. Two review authors read all abstracts and full-text articles and records, assessed quality and extracted outcome data independently. One review author extracted data which were checked by a second review author. We resolved discrepancies by consensus or the involvement of a third review author. For meta-analyses, we planned to use a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the

  20. The Inhibition of Stat5 by a Peptide Aptamer Ligand Specific for the DNA Binding Domain Prevents Target Gene Transactivation and the Growth of Breast and Prostate Tumor Cells

    PubMed Central

    Weber, Axel; Borghouts, Corina; Brendel, Christian; Moriggl, Richard; Delis, Natalia; Brill, Boris; Vafaizadeh, Vida; Groner, Bernd

    2013-01-01

    The signal transducer and activator of transcription Stat5 is transiently activated by growth factor and cytokine signals in normal cells, but its persistent activation has been observed in a wide range of human tumors. Aberrant Stat5 activity was initially observed in leukemias, but subsequently also found in carcinomas. We investigated the importance of Stat5 in human tumor cell lines. shRNA mediated downregulation of Stat5 revealed the dependence of prostate and breast cancer cells on the expression of this transcription factor. We extended these inhibition studies and derived a peptide aptamer (PA) ligand, which directly interacts with the DNA-binding domain of Stat5 in a yeast-two-hybrid screen. The Stat5 specific PA sequence is embedded in a thioredoxin (hTRX) scaffold protein. The resulting recombinant protein S5-DBD-PA was expressed in bacteria, purified and introduced into tumor cells by protein transduction. Alternatively, S5-DBD-PA was expressed in the tumor cells after infection with a S5-DBD-PA encoding gene transfer vector. Both strategies impaired the DNA-binding ability of Stat5, suppressed Stat5 dependent transactivation and caused its intracellular degradation. Our experiments describe a peptide based inhibitor of Stat5 protein activity which can serve as a lead for the development of a clinically useful compound for cancer treatment. PMID:24276378

  1. Immunotherapy with Allergen Peptides

    PubMed Central

    2007-01-01

    Specific allergen immunotherapy (SIT) is disease-modifying and efficacious. However, the use of whole allergen preparations is associated with frequent allergic adverse events during treatment. Many novel approaches are being designed to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity. One approach is the use of short synthetic peptides which representing dominant T cell epitopes of the allergen. Short peptides exhibit markedly reduced capacity to cross link IgE and activate mast cells and basophils, due to lack of tertiary structure. Murine pre-clinical studies have established the feasibility of this approach and clinical studies are currently in progress in both allergic and autoimmune diseases. PMID:20525144

  2. Adsorption of insulin peptide on charged single-walled carbon nanotubes: significant role of ordered water molecules.

    PubMed

    Shen, Jia-Wei; Wu, Tao; Wang, Qi; Kang, Yu; Chen, Xin

    2009-06-02

    Ordered hydration shells: The more ordered hydration shells outside the charged CNT surfaces prevent more compact adsorption of the peptide in the charged CNT systems [picture: see text], but peptide binding strengths on the charged CNT surfaces are stronger due to the electrostatic interaction.Studies of adsorption dynamics and stability for peptides/proteins on single-walled carbon nanotubes (SWNTs) are of great importance for a better understanding of the properties and nature of nanotube-based biosystems. Herein, the dynamics and mechanism of the adsorption of the insulin chain B peptide on different charged SWNTs are investigated by explicit solvent molecular dynamics simulations. The results show that all types of surfaces effectively attract the model peptide. Water molecules play a significant role in peptide adsorption on the surfaces of charged carbon nanotubes (CNTs). Compared to peptide adsorption on neutral CNT surfaces, the more ordered hydration shells outside the tube prevent more compact adsorption of the peptide in charged CNT systems. This shield effect leads to a smaller conformational change and van der Waals interaction between the peptide and surfaces, but peptide binding strengths on charged CNT surfaces are stronger than those on the neutral CNT surface due to the strong electrostatic interaction. The result of these simulations implies the possibility of improving the binding strength of peptides/proteins on CNT surfaces, as well as keeping the integrity of the peptide/protein conformation in peptide/protein-CNT complexes by charging the CNTs.

  3. Bioactive peptides from meat muscle and by-products: generation, functionality and application as functional ingredients.

    PubMed

    Lafarga, Tomas; Hayes, Maria

    2014-10-01

    Bioactive peptides are sequences of between 2-30 amino acids in length that impart a positive health effect to the consumer when ingested. They have been identified from a range of foods, including milk and muscle sources including beef, chicken, pork and marine muscles. The myriad of peptides identified from these sources have known antihypertensive, opioid, antioxidant, antithrombotic and other bioactivities. Indeed, bioactive peptides could play a role in the prevention of diseases associated with the development of metabolic syndrome and mental health diseases. The aim of this work is to present an overview of the bioactive peptides identified in muscle proteins and by-products generated during the processing of meat. The paper looks at the isolation, enrichment and characterisation strategies that have been employed to date to generate bioactive peptides and the potential future applications of these peptides in functional foods for the prevention of heart and mental health problems and obesity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Effects of Different Concentrations of Collagenous Peptide from Fish Scales on Osteoblast Proliferation and Osteoclast Resorption.

    PubMed

    Hu, Chung-Hsuan; Yao, Chun-Hsu; Chan, Tzu-Min; Huang, Teng-Le; Sen, Yang; Huang, Chih-Yang; Ho, Chien-Yi

    2016-08-31

    The incidence of osteoporosis has increased among the elderly population. Establishing a model of bone remodeling for screening new drugs is critical to identify safe and effective treatments for osteoporosis. In this study, we established a platform to investigate the therapeutic effects of collagenous peptides extracted from scales of two kinds of fish, namely, sparidae and chanos. These peptides were prepared using seven concentrations of collagenous peptide: 100, 80, 60, 40, 20, 10 and 1 mg/ml. Experimental results indicated that collagenous peptides promoted the proliferation of osteoblasts and inhibited the proliferation of mature osteoclasts; the effective concentration of collagenous peptide-sparidae was 10 mg/ml and that of collagenous peptide-chanos was 40 mg/ml. These findings demonstrate that, to a certain extent, collagenous peptides extracted from fish scales can be used to prevent osteoporosis to assist bone remodeling.

  5. C-Peptide Test

    MedlinePlus

    ... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... splits apart and forms one molecule of C-peptide and one molecule of insulin . Insulin is the hormone that is vital for the body to use ...

  6. Antimicrobial Peptides: An Introduction.

    PubMed

    Haney, Evan F; Mansour, Sarah C; Hancock, Robert E W

    2017-01-01

    The "golden era" of antibiotic discovery has long passed, but the need for new antibiotics has never been greater due to the emerging threat of antibiotic resistance. This urgency to develop new antibiotics has motivated researchers to find new methods to combat pathogenic microorganisms resulting in a surge of research focused around antimicrobial peptides (AMPs; also termed host defense peptides) and their potential as therapeutics. During the past few decades, more than 2000 AMPs have been identified from a diverse range of organisms (animals, fungi, plants, and bacteria). While these AMPs share a number of common features and a limited number of structural motifs; their sequences, activities, and targets differ considerably. In addition to their antimicrobial effects, AMPs can also exhibit immunomodulatory, anti-biofilm, and anticancer activities. These diverse functions have spurred tremendous interest in research aimed at understanding the activity of AMPs, and various protocols have been described to assess different aspects of AMP function including screening and evaluating the activities of natural and synthetic AMPs, measuring interactions with membranes, optimizing peptide function, and scaling up peptide production. Here, we provide a general overview of AMPs and introduce some of the methodologies that have been used to advance AMP research.

  7. Brain Peptides and Psychopharmacology

    ERIC Educational Resources Information Center

    Arehart-Treichel, Joan

    1976-01-01

    Proteins isolated from the brain and used as drugs can improve and apparently even transfer mental states and behavior. Much of the pioneering work and recent research with humans and animals is reviewed and crucial questions that are being posed about the psychologically active peptides are related. (BT)

  8. Dolastatin 15, a mollusk linear peptide, and Celecoxib, a selective cyclooxygenase-2 inhibitor, prevent preneoplastic colonic lesions and induce apoptosis through inhibition of the regulatory transcription factor NF-κB and an inflammatory protein, iNOS.

    PubMed

    Piplani, Honit; Vaish, Vivek; Sanyal, Sankar Nath

    2012-11-01

    The marine ecosystem is a unique and enormously rich source of natural products with potential chemopreventive applications in cancer. In the present study, we explored the chemopreventive role and the molecular mechanism of Dolastatin, a linear peptide from an Indian Ocean mollusk, and Celecoxib, a well-established cyclooxygenase-2 (COX-2) inhibitor in an individual as well as in a combination regimen in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced colon carcinogenesis in a rat model. After a 6-week treatment with DMH, morphological analysis revealed a marked occurrence of preneoplastic features in the colonic mucosa, whereas histologically well-characterized dysplasia and hyperplasia were observed in DMH-treated animals. Simultaneous administration of Celecoxib and Dolastatin reduced these features significantly. DMH treatment affected the number of apoptotic cells in colonic enterocytes, which reverted to the normal level with the use of Celecoxib and Dolastatin. Inflammation remains the dominant molecular mechanism in the development of multiple plaque lesions, the carcinogenic lesions in a DMH-induced process that may be mediated by COX-2. Western blot and immunofluorescence analysis revealed a higher expression of COX-2 and nuclear factor-κB, the transcription factors responsible for proinflammatory proteins such as TNFα, and also the inducible nitric oxide synthase in the DMH group, which was further recovered significantly with the use of Celecoxib and Dolastatin. In-silico molecular docking analysis of Dolastatin as a ligand with various regulatory proteins suggests that although the peptide failed to dock to COX-2, it successfully did so with inducible nitric oxide synthase, thereby indicating the potential of this inflammatory protein as a molecular anticancer target in colon carcinogenesis.

  9. Peptides and Ageing.

    PubMed

    Khavinson, Vladimir Kh

    2002-01-01

    A technology has been developed for manufacturing of biologically active complex peptide preparations from extracts of different tissues. In particular, the pineal preparation (Epithalamin) augments the in vitro outgrowth of explants from the pineal gland but not from other tissues, the latter being stimulated by peptide preparations from respective tissues. Epithalamin increases melatonin production by the pineal gland of rats, improves immunological parameters in rats and mice, produces anticarcinogenic effects in different experimental models, stimulates antioxidant defenses, and restores the reproductive function in old rats. These effects are combined in the ability of Epithalamin to increase the lifespan in rats, mice, and fruit flies. Many of these effects are reproduced in clinical trials, which have demonstrated the geroprotector activity of Epithalamin in humans. Among the effects of the thymic preparation Thymalin, those related to its ability to stimulate immunity are the most prominent. This ability is associated with anticarcinogenic and geroprotector activities. Clinical trials of the peptide preparations obtained from other organs including the prostate, the cerebral cortex, and the eye retina, have demonstrated beneficial effects reflected by the improvement of the conditions of respective organs. Based on the data about the amino acid compositions of the peptide preparations, novel principles of the design of biologically active short peptides possessing tissue-specific activities has been developed. Dipeptides specific for the thymus and tetrapeptides specific for the heart, liver, brain cortex, and pineal glands stimulate the in vitro outgrowth of explants of respective organs. Interestingly, for eye retina and the pineal gland, a common tetrapeptide Ala-Glu-Asp-Gly (Epitalon) has been designed, probably reflecting the common embryonal origin of these two organs. Epitalon reproduces the effects of Epithalamin including those related to its

  10. Biochemical functionalization of peptide nanotubes with phage displayed peptides

    NASA Astrophysics Data System (ADS)

    Swaminathan, Swathi; Cui, Yue

    2016-09-01

    The development of a general approach for the biochemical functionalization of peptide nanotubes (PNTs) could open up existing opportunities in both fundamental studies as well as a variety of applications. PNTs are spontaneously assembled organic nanostructures made from peptides. Phage display has emerged as a powerful approach for identifying selective peptide binding motifs. Here, we demonstrate for the first time the biochemical functionalization of PNTs via peptides identified from a phage display peptide library. The phage-displayed peptides are shown to recognize PNTs. These advances further allow for the development of bifunctional peptides for the capture of bacteria and the self-assembly of silver particles onto PNTs. We anticipate that these results could provide significant opportunities for using PNTs in both fundamental studies and practical applications, including sensors and biosensors nanoelectronics, energy storage devices, drug delivery, and tissue engineering.

  11. Potent D-peptide inhibitors of HIV-1 entry

    PubMed Central

    Welch, Brett D.; VanDemark, Andrew P.; Heroux, Annie; Hill, Christopher P.; Kay, Michael S.

    2007-01-01

    During HIV-1 entry, the highly conserved gp41 N-trimer pocket region becomes transiently exposed and vulnerable to inhibition. Using mirror-image phage display and structure-assisted design, we have discovered protease-resistant D-amino acid peptides (D-peptides) that bind the N-trimer pocket with high affinity and potently inhibit viral entry. We also report high-resolution crystal structures of two of these D-peptides in complex with a pocket mimic that suggest sources of their high potency. A trimeric version of one of these peptides is the most potent pocket-specific entry inhibitor yet reported by three orders of magnitude (IC50 = 250 pM). These results are the first demonstration that D-peptides can form specific and high-affinity interactions with natural protein targets and strengthen their promise as therapeutic agents. The D-peptides described here address limitations associated with current L-peptide entry inhibitors and are promising leads for the prevention and treatment of HIV/AIDS. PMID:17942675

  12. Antiviral Peptides Targeting the West Nile Virus Envelope Protein▿

    PubMed Central

    Bai, Fengwei; Town, Terrence; Pradhan, Deepti; Cox, Jonathan; Ashish; Ledizet, Michel; Anderson, John F.; Flavell, Richard A.; Krueger, Joanna K.; Koski, Raymond A.; Fikrig, Erol

    2007-01-01

    West Nile virus (WNV) can cause fatal murine and human encephalitis. The viral envelope protein interacts with host cells. A murine brain cDNA phage display library was therefore probed with WNV envelope protein, resulting in the identification of several adherent peptides. Of these, peptide 1 prevented WNV infection in vitro with a 50% inhibition concentration of 67 μM and also inhibited infection of a related flavivirus, dengue virus. Peptide 9, a derivative of peptide 1, was a particularly potent inhibitor of WNV in vitro, with a 50% inhibition concentration of 2.6 μM. Moreover, mice challenged with WNV that had been incubated with peptide 9 had reduced viremia and fatality compared with control animals. Peptide 9 penetrated the murine blood-brain barrier and was found in the brain parenchyma, implying that it may have antiviral activity in the central nervous system. These short peptides serve as the basis for developing new therapeutics for West Nile encephalitis and, potentially, other flaviviruses. PMID:17151121

  13. [Distiller Yeasts Producing Antibacterial Peptides].

    PubMed

    Klyachko, E V; Morozkina, E V; Zaitchik, B Ts; Benevolensky, S V

    2015-01-01

    A new method of controlling lactic acid bacteria contamination was developed with the use of recombinant Saccharomyces cerevisiae strains producing antibacterial peptides. Genes encoding the antibacterial peptides pediocin and plantaricin with codons preferable for S. cerevisiae were synthesized, and a system was constructed for their secretory expression. Recombinant S. cerevisiae strains producing antibacterial peptides effectively inhibit the growth of Lactobacillus sakei, Pediacoccus pentasaceus, Pediacoccus acidilactici, etc. The application of distiller yeasts producing antibacterial peptides enhances the ethanol yield in cases of bacterial contamination. Recombinant yeasts producing the antibacterial peptides pediocin and plantaricin can successfully substitute the available industrial yeast strains upon ethanol production.

  14. Antimicrobial Peptides: An Emerging Category of Therapeutic Agents.

    PubMed

    Mahlapuu, Margit; Håkansson, Joakim; Ringstad, Lovisa; Björn, Camilla

    2016-01-01

    Antimicrobial peptides (AMPs), also known as host defense peptides, are short and generally positively charged peptides found in a wide variety of life forms from microorganisms to humans. Most AMPs have the ability to kill microbial pathogens directly, whereas others act indirectly by modulating the host defense systems. Against a background of rapidly increasing resistance development to conventional antibiotics all over the world, efforts to bring AMPs into clinical use are accelerating. Several AMPs are currently being evaluated in clinical trials as novel anti-infectives, but also as new pharmacological agents to modulate the immune response, promote wound healing, and prevent post-surgical adhesions. In this review, we provide an overview of the biological role, classification, and mode of action of AMPs, discuss the opportunities and challenges to develop these peptides for clinical applications, and review the innovative formulation strategies for application of AMPs.

  15. Peptide Signaling in Plant Development

    PubMed Central

    Katsir, Leron; Davies, Kelli A.; Bergmann, Dominique C.; Laux, Thomas

    2011-01-01

    Cell-to-cell communication is integral to the evolution of multicellularity. In plant development, peptide signals relay information coordinating cell proliferation and differentiation. These peptides are often encoded by gene families and bind to corresponding families of receptors. The precise spatiotemporal expression of signals and their cognate receptors underlies developmental patterning, and expressional and biochemical changes over evolutionary time have likely contributed to the refinement and complexity of developmental programs. Here, we discuss two major plant peptide families which have central roles in plant development: the CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE) peptide family and the EPIDERMAL PATTERNING FACTOR (EPF) family. We discuss how specialization has enabled the CLE peptides to modulate stem cell differentiation in various tissue types, and how differing activities of EPF peptides precisely regulate the stomatal developmental program, and we examine the contributions of these peptide families to plant development from an evolutionary perspective. PMID:21549958

  16. Novel Antimicrobial Peptides That Inhibit Gram Positive Bacterial Exotoxin Synthesis

    PubMed Central

    Merriman, Joseph A.; Nemeth, Kimberly A.; Schlievert, Patrick M.

    2014-01-01

    Gram-positive bacteria, such as Staphylococcus aureus, cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin and signal transduction inhibitors glycerol monolaurate and α-globin and β-globin chains of hemoglobin indicate that their abilities to inhibit exotoxin production by S. aureus are separable from abilities to inhibit growth of the organism. Additionally, our previous studies suggest that inhibition of exotoxin production, in absence of ability to kill S. aureus and normal flora lactobacilli, will prevent colonization by pathogenic S. aureus, while not interfering with lactobacilli colonization. These disparate activities may be important in development of novel anti-infective agents that do not alter normal flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity of hemoglobin peptides further to develop potential agents to prevent S. aureus infections. We tested synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, and two human defensins for ability to inhibit exotoxin production without significantly inhibiting S. aureus growth. All of these peptides were weakly or not inhibitory to bacterial growth. However, the peptides were inhibitory to exotoxin production with increasing activity dependent on increasing numbers of positively-charged amino acids. Additionally, the peptides could be immobilized on agarose beads or have amino acid sequences scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not toxic to human vaginal epithelial cells and do not inhibit growth of normal flora L. crispatus. These peptides may interfere with plasma membrane signal transduction in S. aureus due to their positive charges. PMID:24748386

  17. ABCA1 agonist peptides for the treatment of disease

    DOE PAGES

    Bielicki, John K.

    2016-02-01

    Purpose of review The review summarizes information pertaining to the preclinical development of new apolipoprotein (apo) E mimetic peptides that stimulate cellular cholesterol efflux. Recent findings Small α-helical peptides based on the C-terminal domain of apoE have been developed for therapeutic applications. These peptides stimulate cellular cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1) with high potency, like native apolipoproteins on a molar basis. This potent activity has been related to the unique ability of these peptides to maintain α-helix structure upon dilution. Recent structure-activity studies improving the safety features of these mimetic peptides have greatly improved their potentialmore » for clinical use. Structural features of the class A α-helix motif that induce muscle toxicity and hypertriglyceridemia have been identified. These may have implications for the design of other HDL mimetic peptides. Summary ABCA1 is an integral membrane protein that plays a central role in biology. Its principal function is to mediate the efflux of cholesterol and phospholipid from cells to extracellular apo, preventing a build-up of excess cholesterol in membranes. This process generates HDL particles that perform a variety of functions to protect against disease. A number of these functions can be viewed as directly or indirectly supporting ABCA1 activity, thus constituting a positive feedback system to optimize cellular lipid efflux responses and disease prevention. Consequently, therapeutic approaches that mimic the activities of apos may prove highly effective to combat disease. One such approach involves the use of peptides. The broad biological relevance of ABCA1 suggests these apo mimetic peptides may be useful for the treatment of a number of diseases, such as atherosclerosis, diabetes, and Alzheimer's disease.« less

  18. ABCA1 agonist peptides for the treatment of disease

    SciTech Connect

    Bielicki, John K.

    Purpose of review The review summarizes information pertaining to the preclinical development of new apolipoprotein (apo) E mimetic peptides that stimulate cellular cholesterol efflux. Recent findings Small α-helical peptides based on the C-terminal domain of apoE have been developed for therapeutic applications. These peptides stimulate cellular cholesterol efflux via the ATP-binding cassette transporter A1 (ABCA1) with high potency, like native apolipoproteins on a molar basis. This potent activity has been related to the unique ability of these peptides to maintain α-helix structure upon dilution. Recent structure-activity studies improving the safety features of these mimetic peptides have greatly improved their potentialmore » for clinical use. Structural features of the class A α-helix motif that induce muscle toxicity and hypertriglyceridemia have been identified. These may have implications for the design of other HDL mimetic peptides. Summary ABCA1 is an integral membrane protein that plays a central role in biology. Its principal function is to mediate the efflux of cholesterol and phospholipid from cells to extracellular apo, preventing a build-up of excess cholesterol in membranes. This process generates HDL particles that perform a variety of functions to protect against disease. A number of these functions can be viewed as directly or indirectly supporting ABCA1 activity, thus constituting a positive feedback system to optimize cellular lipid efflux responses and disease prevention. Consequently, therapeutic approaches that mimic the activities of apos may prove highly effective to combat disease. One such approach involves the use of peptides. The broad biological relevance of ABCA1 suggests these apo mimetic peptides may be useful for the treatment of a number of diseases, such as atherosclerosis, diabetes, and Alzheimer's disease.« less

  19. CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis.

    PubMed

    Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

    2016-04-14

    The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.

  20. Avian host defense peptides.

    PubMed

    Cuperus, Tryntsje; Coorens, Maarten; van Dijk, Albert; Haagsman, Henk P

    2013-11-01

    Host defense peptides (HDPs) are important effector molecules of the innate immune system of vertebrates. These antimicrobial peptides are also present in invertebrates, plants and fungi. HDPs display broad-spectrum antimicrobial activities and fulfill an important role in the first line of defense of many organisms. It is becoming increasingly clear that in the animal kingdom the functions of HDPs are not confined to direct antimicrobial actions. Research in mammals has indicated that HDPs have many immunomodulatory functions and are also involved in other physiological processes ranging from development to wound healing. During the past five years our knowledge about avian HDPs has increased considerably. This review addresses our current knowledge on the evolution, regulation and biological functions of HDPs of birds. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. The role of antimicrobial peptides in animal defenses

    NASA Astrophysics Data System (ADS)

    Hancock, Robert E. W.; Scott, Monisha G.

    2000-08-01

    It is becoming clear that the cationic antimicrobial peptides are an important component of the innate defenses of all species of life. Such peptides can be constitutively expressed or induced by bacteria or their products. The best peptides have good activities vs. a broad range of bacterial strains, including antibiotic-resistant isolates. They kill very rapidly, do not easily select resistant mutants, are synergistic with conventional antibiotics, other peptides, and lysozyme, and are able to kill bacteria in animal models. It is known that bacterial infections, especially when treated with antibiotics, can lead to the release of bacterial products such as lipopolysaccharide (LPS) and lipoteichoic acid, resulting in potentially lethal sepsis. In contrast to antibiotics, the peptides actually prevent cytokine induction by bacterial products in tissue culture and human blood, and they block the onset of sepsis in mouse models of endotoxemia. Consistent with this, transcriptional gene array experiments using a macrophage cell line demonstrated that a model peptide, CEMA, blocks the expression of many genes whose transcription was induced by LPS. The peptides do this in part by blocking LPS interaction with the serum protein LBP. In addition, CEMA itself has a direct effect on macrophage gene expression. Because cationic antimicrobial peptides are induced by LPS and are able to dampen the septic response of animal cells to LPS, we propose that, in addition to their role in direct and lysozyme-assisted killing of microbes, they have a role in feedback regulation of cytokine responses. We are currently developing variant peptides as therapeutics against antibiotic-resistant infections.

  2. An update on the potential role of C-peptide in diabetes and osteoporosis.

    PubMed

    Pujia, Arturo; Gazzaruso, Carmine; Montalcini, Tiziana

    2017-12-01

    C-peptide secretion is deficient or absent in type 1 diabetes mellitus. It is well accepted that insulin replacement therapy cannot prevent the development of long-term diabetes-related complications, which can often be disabling or even life-threatening. Several cross-sectional investigations have suggested that residual C-peptide production in patients with type 1 diabetes mellitus would help prevent a number of complications. In animal models of diabetes and in patients with type 1 diabetes mellitus, C-peptide replacement improves renal function, skin and skeletal muscle blood flow, nerve conduction, glucose utilization, and other diabetes-related complications. Recent investigations suggest a new beneficial effect of C-peptide, which to date has never been studied. It is known that osteoporosis is the most prevalent short-term complication in type 1 diabetes mellitus. This review will highlight new insights into the pathophysiology and future therapeutic modalities for osteoporosis in individuals with diabetes. This review provides a concise summary of old and new insights into the role of C-peptide in diabetes-related complications. The data suggest that C-peptide is a bioactive peptide, acting independently of insulin, which binds to a G-protein-coupled membrane binding site in different cell types. By triggering Ca 2+ -dependent intracellular signaling pathways, both Na + , K + -ATPase and endothelial nitric oxide synthase are activated. C-peptide may act on osteoblast cells by ERK 1/2 pathway activation, modulate collagen biosynthesis and RANKL expression. Furthermore, C-peptide-deficient postmenopausal women, not affected by diabetes, have a lower bone mineral density than those with normal C-peptide levels. Taken together these studies encourage further investigations to elucidate the role of C-peptide in preventing bone loss in type 1 diabetes mellitus and in those individuals with C-peptide deficiency and osteoporosis.

  3. Vasonatrin peptide: a unique synthetic natriuretic and vasorelaxing peptide.

    PubMed Central

    Wei, C M; Kim, C H; Miller, V M; Burnett, J C

    1993-01-01

    This study reports the cardiovascular and renal actions of a novel and newly synthesized 27-amino acid peptide termed vasonatrin peptide (VNP). VNP is a chimera of atrial natriuretic peptide (ANP) and C-type natriuretic peptide (CNP). This synthetic peptide possesses the 22-amino acid structure of CNP, which is a cardiovascular selective peptide of endothelial origin and is structurally related to ANP. VNP also possesses the five-amino acid COOH terminus of ANP. The current study demonstrates both in vitro and in vivo that VNP possesses the venodilating actions of CNP, the natriuretic actions of ANP, and unique arterial vasodilating actions not associated with either ANP or CNP. Images PMID:8408658

  4. Comparative Analysis of the Antimicrobial Activities of Plant Defensin-Like and Ultrashort Peptides against Food-Spoiling Bacteria.

    PubMed

    Kraszewska, Joanna; Beckett, Michael C; James, Tharappel C; Bond, Ursula

    2016-07-15

    Antimicrobial peptides offer potential as novel therapeutics to combat food spoilage and poisoning caused by pathogenic and nonpathogenic bacteria. Our previous studies identified the peptide human beta-defensin 3 (HBD3) as a potent antimicrobial agent against a wide range of beer-spoiling bacteria. Thus, HBD3 is an excellent candidate for development as an additive to prevent food and beverage spoilage. To expand the repertoire of peptides with antimicrobial activity against bacteria associated with food spoilage and/or food poisoning, we carried out an in silico discovery pipeline to identify peptides with structure and activity similar to those of HBD3, focusing on peptides of plant origin. Using a standardized assay, we compared the antimicrobial activities of nine defensin-like plant peptides to the activity of HBD3. Only two of the peptides, fabatin-2 and Cp-thionin-2, displayed antimicrobial activity; however, the peptides differed from HBD3 in being sensitive to salt and were thermostable. We also compared the activities of several ultrashort peptides to that of HBD3. One of the peptides, the synthetic tetrapeptide O3TR, displayed biphasic antimicrobial activity but had a narrower host range than HBD3. Finally, to determine if the peptides might act in concert to improve antimicrobial activity, we compared the activities of the peptides in pairwise combinations. The plant defensin-like peptides fabatin-2 and Cp-thionin-2 displayed a synergistic effect with HBD3, while O3TR was antagonistic. Thus, some plant defensin-like peptides are effective antimicrobials and may act in concert with HBD3 to control bacteria associated with food spoilage and food poisoning. Food spoilage and food poisoning caused by bacteria can have major health and economic implications for human society. With the rise in resistance to conventional antibiotics, there is a need to identify new antimicrobials to combat these outbreaks in our food supply. Here we screened plant peptide

  5. Tolerogenic insulin peptide therapy precipitates type 1 diabetes.

    PubMed

    Bergman, Marie-Louise; Lopes-Carvalho, Thiago; Martins, Ana-Catarina; Grieco, Fabio A; Eizirik, Décio L; Demengeot, Jocelyne

    2017-07-03

    Daniel et al. (https://doi.org/10.1084/jem.20110574) have previously published in JEM a study on the preventive effect of tolerogenic vaccination with a strong agonist insulin mimetope in type 1 diabetes. Our study now challenges these results and shows that osmotic pump delivery of the modified insulin peptide R22E did not prevent hyperglycemia, accelerated disease onset, increased its incidence, and worsened insulitis. © 2017 Bergman et al.

  6. Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

    PubMed

    Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

  7. Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.

    PubMed

    Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad

    2018-02-18

    Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Improving Peptide Applications Using Nanotechnology.

    PubMed

    Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

    2016-01-01

    Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

  9. Peptides that influence membrane topology

    NASA Astrophysics Data System (ADS)

    Wong, Gerard C. L.

    2014-03-01

    We examine the mechanism of a range of polypeptides that influence membrane topology, including antimicrobial peptides, cell penetrating peptides, viral fusion peptides, and apoptosis proteins, and show how a combination of geometry, coordination chemistry, and soft matter physics can be used to approach a unified understanding. We will also show how such peptides can impact biomedical problems such as auto-immune diseases (psoriasis, lupus), infectious diseases (viral and bacterial infections), and mitochondrial pathologies (under-regulated apoptosis leads to neurodegenerative diseases whereas over-regulated apoptosis leads to cancer.)

  10. The PeptideAtlas Project.

    PubMed

    Deutsch, Eric W

    2010-01-01

    PeptideAtlas is a multi-species compendium of peptides observed with tandem mass spectrometry methods. Raw mass spectrometer output files are collected from the community and reprocessed through a uniform analysis and validation pipeline that continues to advance. The results are loaded into a database and the information derived from the raw data is returned to the community via several web-based data exploration tools. The PeptideAtlas resource is useful for experiment planning, improving genome annotation, and other data mining projects. PeptideAtlas has become especially useful for planning targeted proteomics experiments.

  11. A fluorescence assay for peptide translocation into mitochondria.

    PubMed

    Martinez-Caballero, Sonia; Peixoto, Pablo M V; Kinnally, Kathleen W; Campo, María Luisa

    2007-03-01

    Translocation of the presequence is an early event in import of preproteins across the mitochondrial inner membrane by the TIM23 complex. Import of signal peptides, whose sequences mimic mitochondrial import presequences, was measured using a novel, qualitative, fluorescence assay in about 1h. This peptide assay was used in conjunction with classical protein import analyses and electrophysiological approaches to examine the mechanisms underlying the functional effects of depleting two TIM23 complex components. Tim23p forms, at least in part, the pore of this complex while Tim44p forms part of the translocation motor. Depletion of Tim23p eliminates TIM23 channel activity, which interferes with both peptide and preprotein translocation. In contrast, depletion of Tim44p disrupts preprotein but not peptide translocation, which has no effect on TIM23 channel activity. Two conclusions were made. First, this fluorescence peptide assay was validated as two different mutants were accurately identified. Hence, this assay could provide a rapid means of screening mutants to identify those that fail an initial step in import, i.e., translocation of the presequence. Second, translocation of signal peptides required normal channel activity and disruption of the presequence translocase-associated motor complex did not modify TIM23 channel activity nor prevent presequence translocation.

  12. Peptides and Food Intake

    PubMed Central

    Sobrino Crespo, Carmen; Perianes Cachero, Aránzazu; Puebla Jiménez, Lilian; Barrios, Vicente; Arilla Ferreiro, Eduardo

    2014-01-01

    The mechanisms for controlling food intake involve mainly an interplay between gut, brain, and adipose tissue (AT), among the major organs. Parasympathetic, sympathetic, and other systems are required for communication between the brain satiety center, gut, and AT. These neuronal circuits include a variety of peptides and hormones, being ghrelin the only orexigenic molecule known, whereas the plethora of other factors are inhibitors of appetite, suggesting its physiological relevance in the regulation of food intake and energy homeostasis. Nutrients generated by food digestion have been proposed to activate G-protein-coupled receptors on the luminal side of enteroendocrine cells, e.g., the L-cells. This stimulates the release of gut hormones into the circulation such as glucagon-like peptide-1 (GLP-1), oxyntomodulin, pancreatic polypeptides, peptide tyrosine tyrosine, and cholecystokinin, which inhibit appetite. Ghrelin is a peptide secreted from the stomach and, in contrast to other gut hormones, plasma levels decrease after a meal and potently stimulate food intake. Other circulating factors such as insulin and leptin relay information regarding long-term energy stores. Both hormones circulate at proportional levels to body fat content, enter the CNS proportionally to their plasma levels, and reduce food intake. Circulating hormones can influence the activity of the arcuate nucleus (ARC) neurons of the hypothalamus, after passing across the median eminence. Circulating factors such as gut hormones may also influence the nucleus of the tractus solitarius (NTS) through the adjacent circumventricular organ. On the other hand, gastrointestinal vagal afferents converge in the NTS of the brainstem. Neural projections from the NTS, in turn, carry signals to the hypothalamus. The ARC acts as an integrative center, with two major subpopulations of neurons influencing appetite, one of them coexpressing neuropeptide Y and agouti-related protein (AgRP) that increases food

  13. Endosomolytic Nano-Polyplex Platform Technology for Cytosolic Peptide Delivery To Inhibit Pathological Vasoconstriction.

    PubMed

    Evans, Brian C; Hocking, Kyle M; Kilchrist, Kameron V; Wise, Eric S; Brophy, Colleen M; Duvall, Craig L

    2015-06-23

    A platform technology has been developed and tested for delivery of intracellular-acting peptides through electrostatically complexed nanoparticles, or nano-polyplexes, formulated from an anionic endosomolytic polymer and cationic therapeutic peptides. This delivery platform has been initially tested and optimized for delivery of two unique vasoactive peptides, a phosphomimetic of heat shock protein 20 and an inhibitor of MAPKAP kinase II, to prevent pathological vasoconstriction (i.e., vasospasm) in human vascular tissue. These peptides inhibit vasoconstriction and promote vasorelaxation by modulating actin dynamics in vascular smooth muscle cells. Formulating these peptides into nano-polyplexes significantly enhances peptide uptake and retention, facilitates cytosolic delivery through a pH-dependent endosomal escape mechanism, and enhances peptide bioactivity in vitro as measured by inhibition of F-actin stress fiber formation. In comparison to treatment with the free peptides, which were endowed with cell-penetrating sequences, the nano-polyplexes significantly increased vasorelaxation, inhibited vasoconstriction, and decreased F-actin formation in the human saphenous vein ex vivo. These results suggest that these formulations have significant potential for treatment of conditions such as cerebral vasospasm following subarachnoid hemorrhage. Furthermore, because many therapeutic peptides include cationic cell-penetrating segments, this simple and modular platform technology may have broad applicability as a cost-effective approach for enhancing the efficacy of cytosolically active peptides.

  14. [Assessment of work ability index in evaluation of small peptides geroprotective effect].

    PubMed

    Bashkireva, A S; Kachan, E Yu

    We have conducted a comparative analysis of the work ability index (WAI) application in evaluation of the effectiveness of small peptides (cytogens) used as geroprotectors in the system of preventive medical nutrition of those working with occupational hazards. Our study revealed the necessity of an inclusion of small peptides into the system of preventive medical nutrition, health promotion in people working with occupational hazards and thus subjected to an accelerated aging. The combined application of peptide geroprotectors makes it possible to restore and enhance adaptive resources as well as to correct work ability and maintain health and well-being in different professional groups.

  15. [Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors.

    PubMed

    Buku, A; Condie, B A; Price, J A; Mezei, M

    2005-09-01

    An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/Fc epsilon RI alpha interactions and, consequently, allergic conditions.

  16. Urinary Peptides in Rett Syndrome.

    ERIC Educational Resources Information Center

    Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

    2002-01-01

    A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

  17. The good taste of peptides.

    PubMed

    Temussi, Piero A

    2012-02-01

    The taste of peptides is seldom one of the most relevant issues when one considers the many important biological functions of this class of molecules. However, peptides generally do have a taste, covering essentially the entire range of established taste modalities: sweet, bitter, umami, sour and salty. The last two modalities cannot be attributed to peptides as such because they are due to the presence of charged terminals and/or charged side chains, thus reflecting only the zwitterionic nature of these compounds and/or the nature of some side chains but not the electronic and/or conformational features of a specific peptide. The other three tastes, that is, sweet, umami and bitter, are represented by different families of peptides. This review describes the main peptides with a sweet, umami or bitter taste and their relationship with food acceptance or rejection. Particular emphasis will be given to the sweet taste modality, owing to the practical and scientific relevance of aspartame, the well-known sweetener, and to the theoretical importance of sweet proteins, the most potent peptide sweet molecules. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

  18. Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic)

    PubMed Central

    Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R.; Matloub, Hani S.; Pritchard, Kirkwood A.; Jaradeh, Safwan S.; Havlik, Robert

    2017-01-01

    Background Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. Methods A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Results Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. Conclusions The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. PMID:26433438

  19. Cumulative Brain Injury from Motor Vehicle-Induced Whole-Body Vibration and Prevention by Human Apolipoprotein A-I Molecule Mimetic (4F) Peptide (an Apo A-I Mimetic).

    PubMed

    Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; Yan, Yuhui; LoGiudice, John; Sanger, James R; Matloub, Hani S; Pritchard, Kirkwood A; Jaradeh, Safwan S; Havlik, Robert

    2015-12-01

    Insidious cumulative brain injury from motor vehicle-induced whole-body vibration (MV-WBV) has not yet been studied. The objective of the present study is to validate whether whole-body vibration for long periods causes cumulative brain injury and impairment of the cerebral function. We also explored a preventive method for MV-WBV injury. A study simulating whole-body vibration was conducted in 72 male Sprague-Dawley rats divided into 9 groups (N = 8): (1) 2-week normal control; (2) 2-week sham control (in the tube without vibration); (3) 2-week vibration (exposed to whole-body vibration at 30 Hz and .5 G acceleration for 4 hours/day, 5 days/week for 2 weeks; vibration parameters in the present study are similar to the most common driving conditions); (4) 4-week sham control; (5) 4-week vibration; (6) 4-week vibration with human apolipoprotein A-I molecule mimetic (4F)-preconditioning; (7) 8-week sham control; (8) 8-week vibration; and (9) 8-week 4F-preconditioning group. All the rats were evaluated by behavioral, physiological, and histological studies of the brain. Brain injury from vibration is a cumulative process starting with cerebral vasoconstriction, squeezing of the endothelial cells, increased free radicals, decreased nitric oxide, insufficient blood supply to the brain, and repeated reperfusion injury to brain neurons. In the 8-week vibration group, which indicated chronic brain edema, shrunken neuron numbers increased and whole neurons atrophied, which strongly correlated with neural functional impairment. There was no prominent brain neuronal injury in the 4F groups. The present study demonstrated cumulative brain injury from MV-WBV and validated the preventive effects of 4F preconditioning. Copyright © 2015 National Stroke Association. All rights reserved.

  20. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model

    PubMed Central

    2010-01-01

    Background The binding of peptide fragments of extracellular peptides to class II MHC is a crucial event in the adaptive immune response. Each MHC allotype generally binds a distinct subset of peptides and the enormous number of possible peptide epitopes prevents their complete experimental characterization. Computational methods can utilize the limited experimental data to predict the binding affinities of peptides to class II MHC. Results We have developed the Regularized Thermodynamic Average, or RTA, method for predicting the affinities of peptides binding to class II MHC. RTA accounts for all possible peptide binding conformations using a thermodynamic average and includes a parameter constraint for regularization to improve accuracy on novel data. RTA was shown to achieve higher accuracy, as measured by AUC, than SMM-align on the same data for all 17 MHC allotypes examined. RTA also gave the highest accuracy on all but three allotypes when compared with results from 9 different prediction methods applied to the same data. In addition, the method correctly predicted the peptide binding register of 17 out of 18 peptide-MHC complexes. Finally, we found that suboptimal peptide binding registers, which are often ignored in other prediction methods, made significant contributions of at least 50% of the total binding energy for approximately 20% of the peptides. Conclusions The RTA method accurately predicts peptide binding affinities to class II MHC and accounts for multiple peptide binding registers while reducing overfitting through regularization. The method has potential applications in vaccine design and in understanding autoimmune disorders. A web server implementing the RTA prediction method is available at http://bordnerlab.org/RTA/. PMID:20089173

  1. Fe(+) chemical ionization of peptides.

    PubMed

    Speir, J P; Gorman, G S; Amster, I J

    1993-02-01

    Laser-desorbed peptide neutral molecules were allowed to react with Fe(+) in a Fourier transform mass spectrometer, using the technique of laser desorption/chemical ionization. The Fe(+) ions are formed by laser ablation of a steel target, as well as by dissociative charge-exchange ionization of ferrocene with Ne(+). Prior to reaction with laser-desorbed peptide molecules, Fe(+) ions undergo 20-100 thermalizin collisions with xenon to reduce the population of excited-state metal ion species. The Fe(+) ions that have not experienced thermalizing collisions undergo charge exchange with peptide molecules. Iron ions that undergo thermalizing collisions before they are allowed to react with peptides are found to undergo charge exchange and to form adduct species [M + Fe(+)] and fragment ions that result from the loss of small, stable molecules, such as H2O, CO, and CO2, from the metal ion-peptide complex.

  2. Phage selection of peptide "microantibodies".

    PubMed

    Fujiwara, Daisuke; Fujii, Ikuo

    2013-01-01

    A bioactive peptide capable of inhibiting protein-protein interactions has the potential to be a molecular tool for biological studies and a therapeutic by disrupting aberrant interactions involved in diseases. We have developed combinatorial libraries of peptides with helix-loop-helix structure, from which the isolated peptides have the constrained structure to reduce entropy costs in binding, resulting in high binding affinities for target molecules. Previously, we designed a de novo peptide of helix-loop-helix structure that we termed a "microantibody." Using the microantibody as a library scaffold, we have constructed a phage-display library to successfully isolate molecular-targeting peptides against a cytokine receptor (granulocyte colony-stimulating factor receptor), a protein kinase (Aurora-A), and a ganglioside (GM1). Protocols in this article describe a general procedure for the library construction and the library screening.

  3. Peptides and peptidomimetics as immunomodulators

    PubMed Central

    Gokhale, Ameya S; Satyanarayanajois, Seetharama

    2014-01-01

    Peptides and peptidomimetics can function as immunomodulating agents by either blocking the immune response or stimulating the immune response to generate tolerance. Knowledge of B- or T-cell epitopes along with conformational constraints is important in the design of peptide-based immunomodulating agents. Work on the conformational aspects of peptides, synthesis and modified amino acid side chains have contributed to the development of a new generation of therapeutic agents for autoimmune diseases and cancer. The design of peptides/peptidomimetics for immunomodulation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, systemic lupus and HIV infection is reviewed. In cancer therapy, peptide epitopes are used in such a way that the body is trained to recognize and fight the cancer cells locally as well as systemically. PMID:25186605

  4. Ovalbumin-derived precursor peptides are transferred sequentially from gp96 and calreticulin to MHC I in the endoplasmic reticulum

    PubMed Central

    Kropp, Laura E.; Garg, Manish; Binder, Robert J.

    2010-01-01

    Cellular peptides generated by proteasomal degradation of proteins in the cytosol and destined for presentation by MHC I are associated with several chaperones. Hsp70, hsp90 and the TCP1-ring complex have been implicated as important cytosolic players for chaperoning these peptides. In this study we report that gp96 and calreticulin are essential for chaperoning peptides in the endoplasmic reticulum. Importantly we demonstrate that cellular peptides are transferred sequentially from gp96 to calreticulin and then to MHC I forming a relay line. Disruption of this relay line by removal of gp96 or calreticulin prevents the binding of peptides by MHC I and hence presentation of the MHC I-peptide complex on the cell surface. Our results are important for understanding how peptides are processed and trafficked within the endoplasmic reticulum before exiting in association with MHC I heavy chains and β2-microglobulin as a trimolecular complex. PMID:20410492

  5. Cyclic peptides and their interaction with peptide coated surfaces

    NASA Astrophysics Data System (ADS)

    Palmer, F.; Tünnemann, R.; Leipert, D.; Stingel, C.; Jung, G.; Hoffmann, V.

    2001-05-01

    Focusing on biochemical and pharmaceutical inhibitor systems the interaction of cyclic peptides with model peptides have been investigated by ATR-FTIR-spectroscopy. Information about the participation of special functional groups e.g. COOH, COO -, NH 3+ or peptide backbone was gathered by observing cyclohexapeptides (c(X 1LX 2LX 3)) which are interacting with covalently coated Si-ATR-crystals ( L-arginine, tripeptide I (aNS), tripeptide II (SNa)). To determine the interaction, further studies about the band sequence (1800-1500 cm -1) for non-adsorbed cyclohexapeptides and for the interaction with the silicon surface (SiOH) were necessary. The spectra of the interacting cyclohexapeptides with the SiOH-groups were treated like reference spectra for the evaluation of the peptide-peptide interaction. Based on these spectra, we can conclude that there is peptide-peptide interaction with the coating and not with the residual OH-groups. Determination of interaction mechanisms was done by spectra which represent adsorbed molecules only. The amount of adsorbed molecules was considerably less than a monolayer. Therefore the intensities of the spectra are about 10 -4 absorbance units. The spectra contain information about both changes of the coating and of the cyclohexapeptide.

  6. Peptide-formation on cysteine-containing peptide scaffolds

    NASA Technical Reports Server (NTRS)

    Chu, B. C.; Orgel, L. E.

    1999-01-01

    Monomeric cysteine residues attached to cysteine-containing peptides by disulfide bonds can be activated by carbonyldiimidazole. If two monomeric cysteine residues, attached to a 'scaffold' peptide Gly-Cys-Glyn-Cys-Glu10, (n = 0, 1, 2, 3) are activated, they react to form the dipeptide Cys-Cys. in 25-65% yield. Similarly, the activation of a cysteine residue attached to the 'scaffold' peptide Gly-Cys-Gly-Glu10 in the presence of Arg5 leads to the formation of Cys-Arg5 in 50% yield. The significance of these results for prebiotic chemistry is discussed.

  7. Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications.

    PubMed

    Spicer, Christopher D; Jumeaux, Coline; Gupta, Bakul; Stevens, Molly M

    2018-05-21

    Peptide- and protein-nanoparticle conjugates have emerged as powerful tools for biomedical applications, enabling the treatment, diagnosis, and prevention of disease. In this review, we focus on the key roles played by peptides and proteins in improving, controlling, and defining the performance of nanotechnologies. Within this framework, we provide a comprehensive overview of the key sequences and structures utilised to provide biological and physical stability to nano-constructs, direct particles to their target and influence their cellular and tissue distribution, induce and control biological responses, and form polypeptide self-assembled nanoparticles. In doing so, we highlight the great advances made by the field, as well as the challenges still faced in achieving the clinical translation of peptide- and protein-functionalised nano-drug delivery vehicles, imaging species, and active therapeutics.

  8. Bioactive Peptides Derived from Seaweed Protein and Their Health Benefits: Antihypertensive, Antioxidant, and Antidiabetic Properties.

    PubMed

    Admassu, Habtamu; Gasmalla, Mohammed Abdalbasit A; Yang, Ruijin; Zhao, Wei

    2018-01-01

    Cardiovascular diseases and diabetes are the biggest causes of death globally. Therefore, prevention of these diseases is a focus of pharmaceuticals and functional food manufacturers. This review summarizes recent research trends and scientific knowledge in seaweed protein-derived peptides with particular emphasis on production, isolation and potential health impacts in prevention of hypertension, diabetes and oxidative stress. The current status and future prospects of bioactive peptides are also discussed. Bioactive peptides have strong potential for use in therapeutic drug and functional food formulation in health management strategy, especially cardiovascular disease and diabetes. Seaweeds can be used as sustainable protein sources in the production of these peptide-based drugs and functional foods for preventing such diseases. Many studies have reported that peptides showing angiotensin converting enzyme inhibition, antihypertensive, antioxidative and antidiabetics activities, have been successfully isolated from seaweed. However, further research is needed in large-scale production of these peptides, efficient isolation methods, interactions with functional foods and other pharmaceuticals, and their ease to digestion in in vivo studies and safety to validate the health benefits of these peptides. © 2017 Institute of Food Technologists®.

  9. Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex

    NASA Astrophysics Data System (ADS)

    Feng, Mei; Bell, David R.; Zhou, Ruhong

    2017-12-01

    The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

  10. Facile and selective covalent grafting of an RGD-peptide to electrospun scaffolds improves HUVEC adhesion.

    PubMed

    Dettin, Monica; Zamuner, Annj; Roso, Martina; Iucci, Giovanna; Samouillan, Valerie; Danesin, Roberta; Modesti, Michele; Conconi, Maria Teresa

    2015-10-01

    The development of a biomimetic surface able to promote endothelialization is fundamental in the search for blood vessel substitutes that prevent the formation of thrombi or hyperplasia. This study aims at investigating the effect of functionalization of poly-ε-caprolactone or poly(L-lactic acid-co-ɛ-caprolactone) electrospun scaffolds with a photoreactive adhesive peptide. The designed peptide sequence contains four Gly-Arg-Gly-Asp-Ser-Pro motifs per chain and a p-azido-Phe residue at each terminus. Different peptide densities on the scaffold surface were obtained by simply modifying the peptide concentration used in pretreatment of the scaffold before UV irradiation. Scaffolds of poly-ε-caprolactone embedded with adhesive peptides were produced to assess the importance of peptide covalent grafting. Our results show that the scaffolds functionalized with photoreactive peptides enhance adhesion at 24 h with a dose-dependent effect and control the proliferation of human umbilical vein endothelial cells, whereas the inclusion of adhesive peptide in the electrospun matrices by embedding does not give satisfactory results. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  11. Selective Algicidal Action of Peptides against Harmful Algal Bloom Species

    PubMed Central

    Park, Seong-Cheol; Lee, Jong-Kook; Kim, Si Wouk; Park, Yoonkyung

    2011-01-01

    Recently, harmful algal bloom (HAB), also termed “red tide”, has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1∼4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal impact on

  12. Selective algicidal action of peptides against harmful algal bloom species.

    PubMed

    Park, Seong-Cheol; Lee, Jong-Kook; Kim, Si Wouk; Park, Yoonkyung

    2011-01-01

    Recently, harmful algal bloom (HAB), also termed "red tide", has been recognized as a serious problem in marine environments according to climate changes worldwide. Many novel materials or methods to prevent HAB have not yet been employed except for clay dispersion, in which can the resulting sedimentation on the seafloor can also cause alteration in marine ecology or secondary environmental pollution. In the current study, we investigated that antimicrobial peptide have a potential in controlling HAB without cytotoxicity to harmless marine organisms. Here, antimicrobial peptides are proposed as new algicidal compounds in combating HAB cells. HPA3 and HPA3NT3 peptides which exert potent antimicrobial activity via pore forming action in plasma membrane showed that HPA3NT3 reduced the motility of algal cells, disrupted their plasma membrane, and induced the efflux of intracellular components. Against raphidoflagellate such as Heterosigma akashiwo, Chattonella sp., and C. marina, it displayed a rapid lysing action in cell membranes at 1~4 µM within 2 min. Comparatively, its lysing effects occurred at 8 µM within 1 h in dinoflagellate such as Cochlodium polykrikoides, Prorocentrum micans, and P. minimum. Moreover, its lysing action induced the lysis of chloroplasts and loss of chlorophyll a. In the contrary, this peptide was not effective against Skeletonema costatum, harmless algal cell, even at 256 µM, moreover, it killed only H. akashiwo or C. marina in co-cultivation with S. costatum, indicating to its selective algicidal activity between harmful and harmless algal cells. The peptide was non-hemolytic against red blood cells of Sebastes schlegeli, the black rockfish, at 120 µM. HAB cells were quickly and selectively lysed following treatment of antimicrobial peptides without cytotoxicity to harmless marine organisms. Thus, the antibiotic peptides examined in our study appear to have much potential in effectively controlling HAB with minimal impact on marine

  13. Marine-Derived Bioactive Peptides for Biomedical Sectors: A Review.

    PubMed

    Ruiz-Ruiz, Federico; Mancera-Andrade, Elena I; Iqbal, Hafiz M N

    2017-01-01

    Marine-based resources such as algae and other marine by-products have been recognized as rich sources of structurally diverse bioactive peptides. Evidently, their structural characteristics including unique amino acid residues are responsible for their biological activity. Several of the above-mentioned marine-origin species show multi-functional bioactivities that are useful for a new discovery and/or reinvention of biologically active ingredients, nutraceuticals and/or pharmaceuticals. Therefore, in recent years, marine-derived bioactive peptides have gained a considerable attention with high-value biomedical and/or pharmaceutical potentials. Furthermore, a wider spectrum of bioactive peptides can be produced through proteolytic-assisted hydrolysis of various marine resources under controlled physicochemical (pH and temperature of the reaction media) environment. Owing to their numerous health-related beneficial effects and therapeutic potential in the treatment and/or prevention of many diseases, such marine-derived bioactive peptides exhibit a wider spectrum of biological activities such as anti-cancerous, anti-proliferative, anti-coagulant, antibacterial, antifungal, and anti-tumor activities among many others. Based on emerging evidence of marine-derived peptide mining, the above-mentioned marine resources contain noteworthy levels of high-value protein. The present review article mainly summarizes the marine-derived bioactive peptides and emphasizing their potential applications in biomedical and/or pharmaceutical sectors of the modern world. In conclusion, recent literature has provided evidence that marine-derived bioactive peptides play a critical role in human health along with many possibilities of designing new functional nutraceuticals and/or pharmaceuticals to clarify potent mechanisms of action for a wider spectrum of diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Food protein-originating peptides as tastants - Physiological, technological, sensory, and bioinformatic approaches.

    PubMed

    Iwaniak, Anna; Minkiewicz, Piotr; Darewicz, Małgorzata; Hrynkiewicz, Monika

    2016-11-01

    Taste is one of the factors based on which the organism makes the selection of what to ingest. It also protects humans from ingesting toxic compounds and is one of the main attributes when thinking about food quality. Five basic taste sensations are recognized by humans: bitter, salty, sour, sweet, and umami. The taste of foods is affected by some molecules of some specific chemical nature. One of them are peptides derived from food proteins. Although they are not the major natural compounds originating from food sources that are responsible for the taste, they are in the area of scientific research due to the specific composition of amino acids which are well-known for their sensory properties. Literature data implicate that sweet, bitter, and umami are the tastes attributable to peptides. Moreover, the bitter peptide tastants are the dominant among the other tastes. Additionally, other biological activities like, e.g., inhibiting enzymes that regulate the body functions and acting as preventive food agents of civilization diseases, are also associated with the taste of peptides. The advance in information technologies has contributed to the elaboration of internet archives (databases) as well as in silico tools for the analysis of biological compounds. It also concerns peptides - namely taste carriers originating from foods. Thus, our paper provides a summary of knowledge about peptides as tastants with special attention paid to the following aspects: a) basis of taste perception, b) taste peptides detected in food protein sequences with special emphasis put on the role of bitter peptides, c) peptides that may enhance/suppress the taste of foods, d) databases as well as bioinformatic approaches suitable to study the taste of peptides, e) taste-taste interactions, f) basis of sensory analysis in the evaluation of the taste of molecules, including peptides, and g) the methodology applied to reduce/eliminate the undesired taste of peptides. The list of taste

  15. Mung bean proteins and peptides: nutritional, functional and bioactive properties

    PubMed Central

    Yi-Shen, Zhu; Shuai, Sun; FitzGerald, Richard

    2018-01-01

    To date, no extensive literature review exists regarding potential uses of mung bean proteins and peptides. As mung bean has long been widely used as a food source, early studies evaluated mung bean nutritional value against the Food and Agriculture Organization of the United Nations (FAO)/the World Health Organization (WHO) amino acids dietary recommendations. The comparison demonstrated mung bean to be a good protein source, except for deficiencies in sulphur-containing amino acids, methionine and cysteine. Methionine and cysteine residues have been introduced into the 8S globulin through protein engineering technology. Subsequently, purified mung bean proteins and peptides have facilitated the study of their structural and functional properties. Two main types of extraction methods have been reported for isolation of proteins and peptides from mung bean flours, permitting sequencing of major proteins present in mung bean, including albumins and globulins (notably 8S globulin). However, the sequence for albumin deposited in the UniProt database differs from other sequences reported in the literature. Meanwhile, a limited number of reports have revealed other useful bioactivities for proteins and hydrolysed peptides, including angiotensin-converting enzyme inhibitory activity, anti-fungal activity and trypsin inhibitory activity. Consequently, several mung bean hydrolysed peptides have served as effective food additives to prevent proteolysis during storage. Ultimately, further research will reveal other nutritional, functional and bioactive properties of mung bean for uses in diverse applications. PMID:29545737

  16. Mung bean proteins and peptides: nutritional, functional and bioactive properties.

    PubMed

    Yi-Shen, Zhu; Shuai, Sun; FitzGerald, Richard

    2018-01-01

    To date, no extensive literature review exists regarding potential uses of mung bean proteins and peptides. As mung bean has long been widely used as a food source, early studies evaluated mung bean nutritional value against the Food and Agriculture Organization of the United Nations (FAO)/the World Health Organization (WHO) amino acids dietary recommendations. The comparison demonstrated mung bean to be a good protein source, except for deficiencies in sulphur-containing amino acids, methionine and cysteine. Methionine and cysteine residues have been introduced into the 8S globulin through protein engineering technology. Subsequently, purified mung bean proteins and peptides have facilitated the study of their structural and functional properties. Two main types of extraction methods have been reported for isolation of proteins and peptides from mung bean flours, permitting sequencing of major proteins present in mung bean, including albumins and globulins (notably 8S globulin). However, the sequence for albumin deposited in the UniProt database differs from other sequences reported in the literature. Meanwhile, a limited number of reports have revealed other useful bioactivities for proteins and hydrolysed peptides, including angiotensin-converting enzyme inhibitory activity, anti-fungal activity and trypsin inhibitory activity. Consequently, several mung bean hydrolysed peptides have served as effective food additives to prevent proteolysis during storage. Ultimately, further research will reveal other nutritional, functional and bioactive properties of mung bean for uses in diverse applications.

  17. Trehalose induced conformational changes in the amyloid-β peptide.

    PubMed

    Khan, Shagufta H; Kumar, Raj

    2017-06-01

    Alzheimer's disease is an irreversible and progressive brain disorder featured by the accumulation of Amyloid-β (Aβ) peptide, which forms insoluble assemblies that builds up into plaques resulting in cognitive decline and memory loss. The formation of fibrillar amyloid deposits is accompanied by conformational changes of the soluble Aβ peptide into β-sheet structures. Strategies to prevent or reduce Aβ aggregation using small molecules such as trehalose have shown beneficial effects under in vitro cell- and in vivo mouse- models. However, the role of trehalose in reducing Aβ peptide aggregation is still not clear. In the present study, using circular dichroism- and fluorescence emission- spectroscopies, we demonstrated that in the presence of trehalose, Aβ peptide adopts more helical content and undergoes a disorder/order conformational transition. Based on our findings, we conclude that trehalose affects the conformation of Aβ peptide to form α-helical structure, which may inhibit the formation of β-sheets and thereby aggregation. Copyright © 2017 Elsevier GmbH. All rights reserved.

  18. Identification of peptides in human Hsp20 and Hsp27 that possess molecular chaperone and anti-apoptotic activities.

    PubMed

    Nahomi, Rooban B; DiMauro, Michael A; Wang, Benlian; Nagaraj, Ram H

    2015-01-01

    Previous studies have identified peptides in the 'crystallin-domain' of the small heat-shock protein (sHSP) α-crystallin with chaperone and anti-apoptotic activities. We found that peptides in heat-shock protein Hsp20 (G71HFSVLLDVKHFSPEEIAVK91) and Hsp27 (D93RWRVSLDVNHFAPDELTVK113) with sequence homology to α-crystallin also have robust chaperone and anti-apoptotic activities. Both peptides inhibited hyperthermic and chemically induced aggregation of client proteins. The scrambled peptides of Hsp20 and Hsp27 showed no such effects. The chaperone activities of the peptides were better than those from αA- and αB-crystallin. HeLa cells took up the FITC-conjugated Hsp20 peptide and, when the cells were thermally stressed, the peptide was translocated from the cytoplasm to the nucleus. The two peptides inhibited apoptosis in HeLa cells by blocking cytochrome c release from the mitochondria and caspase-3 activation. We found that scrambling the last four amino acids in the two peptides (KAIV in Hsp20 and KTLV in Hsp27) made them unable to enter cells and ineffective against stress-induced apoptosis. Intraperitoneal injection of the peptides prevented sodium-selenite-induced cataract formation in rats by inhibiting protein aggregation and oxidative stress. Our study has identified peptides from Hsp20 and Hsp27 that may have therapeutic benefit in diseases where protein aggregation and apoptosis are contributing factors.

  19. Food-derived immunomodulatory peptides.

    PubMed

    Santiago-López, Lourdes; Hernández-Mendoza, Adrián; Vallejo-Cordoba, Belinda; Mata-Haro, Verónica; González-Córdova, Aarón F

    2016-08-01

    Food proteins contain specific amino acid sequences within their structures that may positively impact bodily functions and have multiple immunomodulatory effects. The functional properties of these specific sequences, also referred to as bioactive peptides, are revealed only after the degradation of native proteins during digestion processes. Currently, milk proteins have been the most explored source of bioactive peptides, which presents an interesting opportunity for the dairy industry. However, plant- and animal-derived proteins have also been shown to be important sources of bioactive peptides. This review summarizes the in vitro and in vivo evidence of the role of various food proteins as sources of immunomodulatory peptides and discusses the possible pathways involving these properties. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  20. Modification Site Localization in Peptides.

    PubMed

    Chalkley, Robert J

    2016-01-01

    There are a large number of search engines designed to take mass spectrometry fragmentation spectra and match them to peptides from proteins in a database. These peptides could be unmodified, but they could also bear modifications that were added biologically or during sample preparation. As a measure of reliability for the peptide identification, software normally calculates how likely a given quality of match could have been achieved at random, most commonly through the use of target-decoy database searching (Elias and Gygi, Nat Methods 4(3): 207-214, 2007). Matching the correct peptide but with the wrong modification localization is not a random match, so results with this error will normally still be assessed as reliable identifications by the search engine. Hence, an extra step is required to determine site localization reliability, and the software approaches to measure this are the subject of this part of the chapter.

  1. Peptide nanostructures in biomedical technology.

    PubMed

    Feyzizarnagh, Hamid; Yoon, Do-Young; Goltz, Mark; Kim, Dong-Shik

    2016-09-01

    Nanostructures of peptides have been investigated for biomedical applications due to their unique mechanical and electrical properties in addition to their excellent biocompatibility. Peptides may form fibrils, spheres and tubes in nanoscale depending on the formation conditions. These peptide nanostructures can be used in electrical, medical, dental, and environmental applications. Applications of these nanostructures include, but are not limited to, electronic devices, biosensing, medical imaging and diagnosis, drug delivery, tissue engineering and stem cell research. This review offers a discussion of basic synthesis methods, properties and application of these nanomaterials. The review concludes with recommendations and future directions for peptide nanostructures. WIREs Nanomed Nanobiotechnol 2016, 8:730-743. doi: 10.1002/wnan.1393 For further resources related to this article, please visit the WIREs website. © 2016 Wiley Periodicals, Inc.

  2. Cardioprotective peptides from marine sources.

    PubMed

    Harnedy, Padraigín A; FitzGerald, Richard J

    2013-05-01

    Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.

  3. Biomedical Applications of Organometal-Peptide Conjugates

    NASA Astrophysics Data System (ADS)

    Metzler-Nolte, Nils

    Peptides are well suited as targeting vectors for the directed delivery of metal-based drugs or probes for biomedical investigations. This chapter describes synthetic strategies for the preparation of conjugates of medically interesting peptides with covalently bound metal complexes. Peptides that were used include neuropeptides (enkephalin, neuropeptide Y, neurotensin), uptake peptides (TAT and poly-Arg), and intracellular localization sequences. To these peptides, a whole variety of transition metal complexes has been attached in recent years by solid-phase peptide synthesis (SPPS) techniques. The metal complex can be attached to the peptide on the resin as part of the SPPS scheme. Alternatively, the metal complex may be attached to the peptide as a postsynthetic modification. Advantages as well as disadvantages for either strategy are discussed. Biomedical applications include radiopharmaceutical applications, anticancer and antibacterial activity, metal-peptide conjugates as targeted CO-releasing molecules, and metal-peptide conjugates in biosensor applications.

  4. The use of chimeric vimentin citrullinated peptides for the diagnosis of rheumatoid arthritis.

    PubMed

    Malakoutikhah, Morteza; Gómara, María J; Gómez-Puerta, José A; Sanmartí, Raimon; Haro, Isabel

    2011-11-10

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and, in many cases, destruction of the joints. To prevent progressive and irreversible structural damage, early diagnosis of RA is of paramount importance. The present study addresses the search of new RA citrullinated antigens that could supplement or complement diagnostic/prognostic existing tests. With this aim, the epitope anticitrullinated vimentin antibody response was mapped using synthetic peptides. To improve the sensitivity/specificity balance, a vimentin peptide that was selected, and its cyclic analogue, were combined with fibrin- and filaggrin-related peptides to render chimeric peptides. Our findings highlight the putative application of these chimeric peptides for the design of RA diagnosis systems and imply that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported here (fibrin, vimentin, filaggrin) has a specific utility in the identification of a particular subset of RA patients.

  5. Effect of Curcumin on the metal ion induced fibrillization of Amyloid-β peptide

    NASA Astrophysics Data System (ADS)

    Banerjee, Rona

    2014-01-01

    The effect of Curcumin on Cu(II) and Zn(II) induced oligomerization and protofibrillization of the amyloid-beta (Aβ) peptide has been studied by spectroscopic and microscopic methods. Curcumin could significantly reduce the β-sheet content of the peptide in a time dependent manner. It also plays an antagonistic role in β-sheet formation that is promoted by metal ions like Cu(II) and Zn(II) as observed by Circular Dichroism (CD) spectroscopy. Atomic force microscopic (AFM) images show that spontaneous fibrillization of the peptide occurs in presence of Cu(II) and Zn(II) but is inhibited on incubation of the peptide with Curcumin indicating the beneficial role of Curcumin in preventing the aggregation of Aβ peptide.

  6. Plant peptides in defense and signaling.

    PubMed

    Marmiroli, Nelson; Maestri, Elena

    2014-06-01

    This review focuses on plant peptides involved in defense against pathogen infection and those involved in the regulation of growth and development. Defense peptides, defensins, cyclotides and anti-microbial peptides are compared and contrasted. Signaling peptides are classified according to their major sites of activity. Finally, a network approach to creating an interactomic peptide map is described. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Flanking signal and mature peptide residues influence signal peptide cleavage

    PubMed Central

    Choo, Khar Heng; Ranganathan, Shoba

    2008-01-01

    Background Signal peptides (SPs) mediate the targeting of secretory precursor proteins to the correct subcellular compartments in prokaryotes and eukaryotes. Identifying these transient peptides is crucial to the medical, food and beverage and biotechnology industries yet our understanding of these peptides remains limited. This paper examines the most common type of signal peptides cleavable by the endoprotease signal peptidase I (SPase I), and the residues flanking the cleavage sites of three groups of signal peptide sequences, namely (i) eukaryotes (Euk) (ii) Gram-positive (Gram+) bacteria, and (iii) Gram-negative (Gram-) bacteria. Results In this study, 2352 secretory peptide sequences from a variety of organisms with amino-terminal SPs are extracted from the manually curated SPdb database for analysis based on physicochemical properties such as pI, aliphatic index, GRAVY score, hydrophobicity, net charge and position-specific residue preferences. Our findings show that the three groups share several similarities in general, but they display distinctive features upon examination in terms of their amino acid compositions and frequencies, and various physico-chemical properties. Thus, analysis or prediction of their sequences should be separated and treated as distinct groups. Conclusion We conclude that the peptide segment recognized by SPase I extends to the start of the mature protein to a limited extent, upon our survey of the amino acid residues surrounding the cleavage processing site. These flanking residues possibly influence the cleavage processing and contribute to non-canonical cleavage sites. Our findings are applicable in defining more accurate prediction tools for recognition and identification of cleavage site of SPs. PMID:19091014

  8. Lactoferrin-derived Peptides Active towards Influenza: Identification of Three Potent Tetrapeptide Inhibitors.

    PubMed

    Scala, Maria Carmina; Sala, Marina; Pietrantoni, Agostina; Spensiero, Antonia; Di Micco, Simone; Agamennone, Mariangela; Bertamino, Alessia; Novellino, Ettore; Bifulco, Giuseppe; Gomez-Monterrey, Isabel M; Superti, Fabiana; Campiglia, Pietro

    2017-09-06

    Bovine lactoferrin is a biglobular multifunctional iron binding glycoprotein that plays an important role in innate immunity against infections. We have previously demonstrated that selected peptides from bovine lactoferrin C-lobe are able to prevent both Influenza virus hemagglutination and cell infection. To deeper investigate the ability of lactoferrin derived peptides to inhibit Influenza virus infection, in this study we identified new bovine lactoferrin C-lobe derived sequences and corresponding synthetic peptides were synthesized and assayed to check their ability to prevent viral hemagglutination and infection. We identified three tetrapeptides endowed with broad anti-Influenza activity and able to inhibit viral infection in a concentration range femto- to picomolar. Our data indicate that these peptides may constitute a non-toxic tool for potential applications as anti-Influenza therapeutics.

  9. CXCR4-antagonist Peptide R-liposomes for combined therapy against lung metastasis

    NASA Astrophysics Data System (ADS)

    Ieranò, Caterina; Portella, Luigi; Lusa, Sara; Salzano, Giuseppina; D'Alterio, Crescenzo; Napolitano, Maria; Buoncervello, Maria; Macchia, Daniele; Spada, Massimo; Barbieri, Antonio; Luciano, Antonio; Barone, Maria Vittoria; Gabriele, Lucia; Caraglia, Michele; Arra, Claudio; De Rosa, Giuseppe; Scala, Stefania

    2016-03-01

    The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide R were developed (PL-Peptide R). In vitro PL-Peptide R efficiently inhibited CXCR4-dependent migration and in vivo it significantly reduced lung metastases and increased overall survival in B16-CXCR4 injected C57BL/6 mice. To evaluate if PL-Peptide R could also be a drug delivery system for CXCR4 expressing tumors, the PL-Peptide R was loaded with doxorubicin (DOX) (PL-Peptide R-DOX). PL-Peptide R-DOX efficiently delivered DOX to CXCR4 expressing cell lines with a consequent decrease in the DOX IC50 efficient dose. In vivo, B16-CXCR4 injected C57BL/6 mice treated with PL-Peptide R-DOX developed fewer lung metastases compared to PL-DOX treated mice. This work provides the proof-of-concept to prevent metastasis by using combined nanomedicine.The chemokine CXCL12 activates CXCR4, initiating multiple pathways that control immune cell trafficking, angiogenesis and embryogenesis; CXCR4 is also overexpressed in multiple tumors affecting metastatic dissemination. While there has been great enthusiasm for exploiting the CXCR4-CXCL12 axis as a target in cancer therapy, to date the promise has yet to be fulfilled. A new class of CXCR4-antagonist cyclic peptides was recently developed and the compound named Peptide R was identified as the most active. With the intent to improve the efficacy and biodistribution of Peptide R, stealth liposomes decorated with Peptide

  10. Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

    PubMed

    Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

    2016-01-01

    This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

  11. Intestinal immunomodulation. Role of regulative peptides and promising pharmacological activities.

    PubMed

    Motilva, V; Talero, E; Calvo, J R; Villegas, I; Alarcón-de-la-Lastra, C; Sánchez-Fidalgo, S

    2008-01-01

    About 50 peptides, and a similar number of peptide receptors, are known to be present in the gut and this amount is likely to rise significantly over the next few years. While there has been a massive research effort to define their functions and their anatomical distribution in the central nervous system (CNS), the understanding of their roles in the gut is far more limited. Classically, the physiological functions include the control of motility, fluids, electrolytes, and digestive enzymes secretion, or vascular and visceral pain function, and more recently, the role-played in cell proliferation and survival, and in immune-inflammatory responses. The term inflammatory bowel disease (IBD) that encompasses Crohn's disease and ulcerative colitis, is clearly an inflammatory disease where several mediators such as cytokines, chemokines, prostanoids, nitric oxide or free radicals, produced by infiltrating cells, play a critical role in intestine tissue alteration. Some peptides, initially known for their neuroregulative properties, have been suggested to act as endogenous immune factors, with predominant antiinflammatory effects. Based on these actions, these molecules are proposed as potential agents for the treatment of IBD and selective peptide analogs are being developed as novel therapeutic strategies for IBD patients. Patients with IBD have an increased risk for developing colorectal cancer (CRC). Up to the present time, no known genetic basis has been identified to explain CRC predisposition in these IBD. Instead, it is assumed that chronic inflammation is what causes cancer. This is supported by the fact that colon cancer risk increases with longer duration of colitis, greater anatomic extent of colitis, the concomitant presence of other inflammatory manifestations, and the fact that certain drugs used to treat inflammation, may prevent the development of CRC. However, though different regulative peptides play a beneficial role in experimental IBD, an

  12. What peptides these deltorphins be.

    PubMed

    Lazarus, L H; Bryant, S D; Cooper, P S; Salvadori, S

    1999-02-01

    The deltorphins are a class of highly selective delta-opioid heptapeptides from the skin of the Amazonian frogs Phyllomedusa sauvagei and P. bicolor. The first of these fascinating peptides came to light in 1987 by cloning of the cDNA of from frog skins, while the other members of this family were identified either by cDNA or isolation of the peptides. The distinctive feature of deltorphins is the presence of a naturally occurring D-enantiomer at the second position in their common N-terminal sequence, Tyr-D-Xaa-Phe, comparable to dermorphin, which is the prototype of a group of mu-selective opioids from the same source. The D-amino acid and the anionic residues, either Glu or Asp, as well as their unique amino acid compositions are responsible for the remarkable biostability, high delta-receptor affinity, bioactivity and peptide conformation. This review summarizes a decade of research from many laboratories that defined which residues and substituents in the deltorphins interact with the delta-receptor and characterized pharmacological and physiological activities in vitro and in vivo. It begins with a historical description of the topic and presents general schema for the synthesis of peptide analogues of deltorphins A, B and C as a means to document the methods employed in producing a myriad of analogues. Structure activity studies of the peptides and their pharmacological activities in vitro are detailed in abundantly tabulated data. A brief compendium of the current level of knowledge of the delta-receptor assists the reader to appreciate the rationale for the design of these analogues. Discussion of the conformation of these peptides addresses how structure leads to further hypotheses regarding ligand receptor interaction. The review ends with a broad discussion of the potential applications of these peptides in clinical and therapeutic settings.

  13. The chromatography-free release, isolation and purification of recombinant peptide for fibril self-assembly.

    PubMed

    Hartmann, B M; Kaar, W; Yoo, I K; Lua, L H L; Falconer, R J; Middelberg, A P J

    2009-12-01

    One of the major expenses associated with recombinant peptide production is the use of chromatography in the isolation and purification stages of a bioprocess. Here we report a chromatography-free isolation and purification process for recombinant peptide expressed in Escherichia coli (E. coli). Initial peptide release is by homogenization and then by enzymatic cleavage of the peptide-containing fusion protein, directly in the E. coli homogenate. Release is followed by selective solvent precipitation (SSP) to isolate and purify the peptide away from larger cell contaminants. Specifically, we expressed in E. coli the self-assembling beta-sheet forming peptide P(11)-2 in fusion to thioredoxin. Homogenate was heat treated (55 degrees C, 15 min) and then incubated with tobacco etch virus protease (TEVp) to release P(11)-2 having a native N-terminus. SSP with ethanol at room temperature then removed contaminating proteins in an integrated isolation-purification step; it proved necessary to add 250 mM NaCl to homogenate to prevent P(11)-2 from partitioning to the precipitate. This process structure gave recombinant P(11)-2 peptide at 97% polypeptide purity and 40% overall yield, without a single chromatography step. Following buffer-exchange of the 97% pure product by bind-elute chromatography into defined chemical conditions, the resulting peptide was shown to be functionally active and able to form self-assembled fibrils. To the best of our knowledge, this manuscript reports the first published process for chromatography-free recombinant peptide release, isolation and purification. The process proved able to deliver functional recombinant peptide at high purity and potentially low cost, opening cost-sensitive materials applications for peptide-based materials.

  14. Differential stability of therapeutic peptides with different proteolytic cleavage sites in blood, plasma and serum.

    PubMed

    Böttger, Roland; Hoffmann, Ralf; Knappe, Daniel

    2017-01-01

    Proteolytic degradation of peptide-based drugs is often considered as major weakness limiting systemic therapeutic applications. Therefore, huge efforts are typically devoted to stabilize sequences against proteases present in serum or plasma, obtained as supernatants after complete blood coagulation or centrifugation of blood supplemented with anticoagulants, respectively. Plasma and serum are reproducibly obtained from animals and humans allowing consistent for clinical analyses and research applications. However, the spectrum of active or activated proteases appears to vary depending on the activation of proteases and cofactors during coagulation (serum) or inhibition of such enzymes by anticoagulants (plasma), such as EDTA (metallo- and Ca2+-dependent proteases) and heparin (e.g. thrombin, factor Xa). Here, we studied the presumed effects on peptide degradation by taking blood via cardiac puncture of CD-1 mice using a syringe containing a peptide solution. Due to absence of coagulation activators (e.g. glass surfaces and damaged cells), visible blood clotting was prevented allowing to study peptide degradation for one hour. The remaining peptide was quantified and the degradation products were identified using mass spectrometry. When the degradation rates (half-life times) were compared to serum derived freshly from the same animal and commercial serum and plasma samples, peptides of three different families showed indeed considerably different stabilities. Generally, peptides were faster degraded in serum than in plasma, but surprisingly all peptides were more stable in fresh blood and the order of degradation rates among the peptides varied among the six different incubation experiments. This indicates, that proteolytic degradation of peptide-based therapeutics may often be misleading stimulating efforts to stabilize peptides at degradation sites relevant only in vitro, i.e., for serum or plasma stability assays, but of lower importance in vivo.

  15. Expression and purification of the antimicrobial peptide GSL1 in bacteria for raising antibodies.

    PubMed

    Meiyalaghan, Sathiyamoorthy; Latimer, Julie M; Kralicek, Andrew V; Shaw, Martin L; Lewis, John G; Conner, Anthony J; Barrell, Philippa J

    2014-11-04

    The Gibberellin Stimulated-Like (GSL) or Snakin peptides from higher plants are cysteine-rich, with broad spectrum activity against a range of bacterial and fungal pathogens. To detect GSL peptides in applications such as western blot analysis and enzyme-linked immunosorbent assays (ELISA), specific antibodies that recognise GSL peptides are required. However, the intrinsic antimicrobial activity of these peptides is likely to prevent their expression alone in bacterial or yeast expression systems for subsequent antibody production in animal hosts. To overcome this issue we developed an Escherichia coli expression strategy based on the expression of the GSL1 peptide as a His-tagged thioredoxin fusion protein. The DNA sequence for the mature GSL1 peptide from potato (Solanum tuberosum L.) was cloned into the pET-32a expression vector to produce a construct encoding N-terminally tagged his6-thioredoxin-GSL1. The fusion protein was overexpressed in E. coli to produce soluble non-toxic protein. The GSL1 fusion protein could be easily purified by using affinity chromatography to yield ~1.3 mg of his6-thioredoxin-GSL1 per L of culture. The fusion protein was then injected into rabbits for antibody production. Western blot analysis showed that the antibodies obtained from rabbit sera specifically recognised the GSL1 peptide that had been expressed in a wheat germ cell-free expression system. We present here the first report of a GSL1 peptide expressed as a fusion protein with thioredoxin that has resulted in milligram quantities of soluble protein to be produced. We have also demonstrated that a wheat germ system can be used to successfully express small quantities of GSL1 peptide useful as positive control in western blot analysis. To our knowledge this is the first report of antibodies being produced against GSL1 peptide. The antibodies will be useful for analysis of GSL1peptides in western blot, localization by immunohistochemistry (IHC) and quantitation by ELISA.

  16. Antimicrobial peptides extend lifespan in Drosophila

    PubMed Central

    Mori, Tetsushi; Carrera, Pilar; Schroer, Jonas; Takeyama, Haruko

    2017-01-01

    Antimicrobial peptides (AMPs) are important defense molecules of the innate immune system. High levels of AMPs are induced in response to infections to fight pathogens, whereas moderate levels induced by metabolic stress are thought to shape commensal microbial communities at barrier tissues. We expressed single AMPs in adult flies either ubiquitously or in the gut by using the inducible GeneSwitch system to tightly regulate AMP expression. We found that activation of single AMPs, including Drosocin, resulted in a significant extension of Drosophila lifespan. These animals showed reduced activity of immune pathways over lifetime, less intestinal regenerative processes, reduced stress response and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin induction protected the animals against infections with the natural Drosophila pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented the lifespan extending effect of Drosocin. Our study provides new insights into the crosstalk of innate immunity, intestinal homeostasis and ageing. PMID:28520752

  17. Antimicrobial peptides extend lifespan in Drosophila.

    PubMed

    Loch, Gerrit; Zinke, Ingo; Mori, Tetsushi; Carrera, Pilar; Schroer, Jonas; Takeyama, Haruko; Hoch, Michael

    2017-01-01

    Antimicrobial peptides (AMPs) are important defense molecules of the innate immune system. High levels of AMPs are induced in response to infections to fight pathogens, whereas moderate levels induced by metabolic stress are thought to shape commensal microbial communities at barrier tissues. We expressed single AMPs in adult flies either ubiquitously or in the gut by using the inducible GeneSwitch system to tightly regulate AMP expression. We found that activation of single AMPs, including Drosocin, resulted in a significant extension of Drosophila lifespan. These animals showed reduced activity of immune pathways over lifetime, less intestinal regenerative processes, reduced stress response and a delayed loss of gut barrier integrity. Furthermore, intestinal Drosocin induction protected the animals against infections with the natural Drosophila pathogen Pseudomonas entomophila, whereas a germ-reduced environment prevented the lifespan extending effect of Drosocin. Our study provides new insights into the crosstalk of innate immunity, intestinal homeostasis and ageing.

  18. Perspectives and Peptides of the Next Generation

    NASA Astrophysics Data System (ADS)

    Brogden, Kim A.

    Shortly after their discovery, antimicrobial peptides from prokaryotes and eukaryotes were recognized as the next potential generation of pharmaceuticals to treat antibiotic-resistant bacterial infections and septic shock, to preserve food, or to sanitize surfaces. Initial research focused on identifying the spectrum of antimicrobial agents, determining the range of antimicrobial activities against bacterial, fungal, and viral pathogens, and assessing the antimicrobial activity of synthetic peptides versus their natural counterparts. Subsequent research then focused on the mechanisms of antimicrobial peptide activity in model membrane systems not only to identify the mechanisms of antimicrobial peptide activity in microorganisms but also to discern differences in cytotoxicity for prokaryotic and eukaryotic cells. Recent, contemporary work now focuses on current and future efforts to construct hybrid peptides, peptide congeners, stabilized peptides, peptide conjugates, and immobilized peptides for unique and specific applications to control the growth of microorganisms in vitro and in vivo.

  19. Sequencing Cyclic Peptides by Multistage Mass Spectrometry

    PubMed Central

    Mohimani, Hosein; Yang, Yu-Liang; Liu, Wei-Ting; Hsieh, Pei-Wen; Dorrestein, Pieter C.; Pevzner, Pavel A.

    2012-01-01

    Some of the most effective antibiotics (e.g., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. While hundreds of biomedically important cyclic peptides have been sequenced, the computational techniques for sequencing cyclic peptides are still in their infancy. Previous methods for sequencing peptide antibiotics and other cyclic peptides are based on Nuclear Magnetic Resonance spectroscopy, and require large amount (miligrams) of purified materials that, for most compounds, are not possible to obtain. Recently, development of mass spectrometry based methods has provided some hope for accurate sequencing of cyclic peptides using picograms of materials. In this paper we develop a method for sequencing of cyclic peptides by multistage mass spectrometry, and show its advantages over single stage mass spectrometry. The method is tested on known and new cyclic peptides from Bacillus brevis, Dianthus superbus and Streptomyces griseus, as well as a new family of cyclic peptides produced by marine bacteria. PMID:21751357

  20. Exploration of the Medicinal Peptide Space.

    PubMed

    Gevaert, Bert; Stalmans, Sofie; Wynendaele, Evelien; Taevernier, Lien; Bracke, Nathalie; D'Hondt, Matthias; De Spiegeleer, Bart

    2016-01-01

    The chemical properties of peptide medicines, known as the 'medicinal peptide space' is considered a multi-dimensional subset of the global peptide space, where each dimension represents a chemical descriptor. These descriptors can be linked to biofunctional, medicinal properties to varying degrees. Knowledge of this space can increase the efficiency of the peptide-drug discovery and development process, as well as advance our understanding and classification of peptide medicines. For 245 peptide drugs, already available on the market or in clinical development, multivariate dataexploration was performed using peptide relevant physicochemical descriptors, their specific peptidedrug target and their clinical use. Our retrospective analysis indicates that clusters in the medicinal peptide space are located in a relatively narrow range of the physicochemical space: dense and empty regions were found, which can be explored for the discovery of novel peptide drugs.

  1. Bioactive peptides derived from traditional Chinese medicine and traditional Chinese food: A review.

    PubMed

    Liu, Ming; Wang, Yunpu; Liu, Yuhuan; Ruan, Roger

    2016-11-01

    There is an urgent treat of numerous chronic diseases including heart disease, stroke, cancer, chronic respiratory diseases and diabetes, which have a significant influence on the health of people worldwide. In addition to numerous preventive and therapeutic drug treatments, important advances have been achieved in the identification of bioactive peptides that may contribute to long-term health. Although bioactive peptides with various biological activities received unprecedented attention, as a new source of bioactive peptides, the significant role of bioactive peptides from traditional Chinese medicine and traditional Chinese food has not fully appreciated compared to other bioactive components. Hence, identification and bioactivity assessment of these peptides could benefit the pharmaceutical and food industry. Furthermore, the functional properties of bioactive peptides help to demystify drug properties and health benefits of traditional Chinese medicine and traditional Chinese food. This paper reviews the generation and biofunctional properties of various bioactive peptides derived from traditional Chinese medicine and traditional Chinese food. Mechanisms of digestion, bioavailability of bioactive peptides and interactions between traditional Chinese medicine and traditional Chinese food are also summarized in this review. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. The Plasma Membrane as a Reservoir, Protective Shield, and Light-Triggered Launch Pad for Peptide Therapeutics.

    PubMed

    O'Banion, Colin P; Nguyen, Luong T; Wang, Qunzhao; Priestman, Melanie A; Holly, Stephen P; Parise, Leslie V; Lawrence, David S

    2016-01-18

    Although peptide-based therapeutics are finding increasing application in the clinic, extensive structural modification is typically required to prevent their rapid degradation by proteases in the blood. We have evaluated the ability of erythrocytes to serve as reservoirs, protective shields (against proteases), and light-triggered launch pads for peptides. We designed lipidated peptides that are anchored to the surface of red blood cells, which furnishes a protease-resistant environment. A photocleavable moiety is inserted between the lipid anchor and the peptide backbone, thereby enabling light-triggered peptide release from erythrocytes. We have shown that a cell-permeable peptide, a hormone (melanocyte stimulating hormone), and a blood-clotting agent can be anchored to erythrocytes, protected from proteases, and photolytically released to create the desired biological effect. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Antimicrobial Peptides in Biomedical Device Manufacturing.

    PubMed

    Riool, Martijn; de Breij, Anna; Drijfhout, Jan W; Nibbering, Peter H; Zaat, Sebastian A J

    2017-01-01

    Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints, and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures, and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured/3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe

  4. Antimicrobial Peptides in Biomedical Device Manufacturing

    NASA Astrophysics Data System (ADS)

    Riool, Martijn; de Breij, Anna; Drijfhout, Jan W.; Nibbering, Peter H.; Zaat, Sebastian A. J.

    2017-08-01

    Over the past decades the use of medical devices, such as catheters, artificial heart valves, prosthetic joints and other implants, has grown significantly. Despite continuous improvements in device design, surgical procedures and wound care, biomaterial-associated infections (BAI) are still a major problem in modern medicine. Conventional antibiotic treatment often fails due to the low levels of antibiotic at the site of infection. The presence of biofilms on the biomaterial and/or the multidrug-resistant phenotype of the bacteria further impair the efficacy of antibiotic treatment. Removal of the biomaterial is then the last option to control the infection. Clearly, there is a pressing need for alternative strategies to prevent and treat BAI. Synthetic antimicrobial peptides (AMPs) are considered promising candidates as they are active against a broad spectrum of (antibiotic-resistant) planktonic bacteria and biofilms. Moreover, bacteria are less likely to develop resistance to these rapidly-acting peptides. In this review we highlight the four main strategies, three of which applying AMPs, in biomedical device manufacturing to prevent BAI. The first involves modification of the physicochemical characteristics of the surface of implants. Immobilization of AMPs on surfaces of medical devices with a variety of chemical techniques is essential in the second strategy. The main disadvantage of these two strategies relates to the limited antibacterial effect in the tissue surrounding the implant. This limitation is addressed by the third strategy that releases AMPs from a coating in a controlled fashion. Lastly, AMPs can be integrated in the design and manufacturing of additively manufactured / 3D-printed implants, owing to the physicochemical characteristics of the implant material and the versatile manufacturing technologies compatible with antimicrobials incorporation. These novel technologies utilizing AMPs will contribute to development of novel and safe

  5. Surface Mediated Self-Assembly of Amyloid Peptides

    NASA Astrophysics Data System (ADS)

    Fakhraai, Zahra

    2015-03-01

    Amyloid fibrils have been considered as causative agents in many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, type II diabetes and amyloidosis. Amyloid fibrils form when proteins or peptides misfold into one dimensional crystals of stacked beta-sheets. In solution, amyloid fibrils form through a nucleation and growth mechanism. The rate limiting nucleation step requires a critical concentration much larger than those measured in physiological conditions. As such the exact origins of the seeds or oligomers that result in the formation of fully mature fibrils in the body remain topic intense studies. It has been suggested that surfaces and interfaces can enhance the fibrillization rate. However, studies of the mechanism and kinetics of the surface-mediated fibrillization are technologically challenging due to the small size of the oligomer and protofibril species. Using smart sample preparation technique to dry the samples after various incubation times we are able to study the kinetics of fibril formation both in solution and in the vicinity of various surfaces using high-resolution atomic force microscopy. These studies elucidate the role of surfaces in catalyzing amyloid peptide formation through a nucleation-free process. The nucleation free self-assembly is rapid and requires much smaller concentrations of peptides or proteins. We show that this process resembles diffusion limited aggregation and is governed by the peptide adhesion rate, two -dimensional diffusion of the peptides on the surface, and preferential interactions between the peptides. These studies suggest an alternative pathway for amyloid formation may exist, which could lead to new criteria for disease prevention and alternative therapies. Research was partially supported by a seed grant from the National Institute of Aging of the National Institutes of Health (NIH) under Award Number P30AG010124 (PI: John Trojanowski) and the University of Pennsylvania.

  6. Twilight reloaded: the peptide experience

    PubMed Central

    Weichenberger, Christian X.; Pozharski, Edwin; Rupp, Bernhard

    2017-01-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallo­graphic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein–peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided. PMID:28291756

  7. Twilight reloaded: the peptide experience.

    PubMed

    Weichenberger, Christian X; Pozharski, Edwin; Rupp, Bernhard

    2017-03-01

    The de facto commoditization of biomolecular crystallography as a result of almost disruptive instrumentation automation and continuing improvement of software allows any sensibly trained structural biologist to conduct crystallographic studies of biomolecules with reasonably valid outcomes: that is, models based on properly interpreted electron density. Robust validation has led to major mistakes in the protein part of structure models becoming rare, but some depositions of protein-peptide complex structure models, which generally carry significant interest to the scientific community, still contain erroneous models of the bound peptide ligand. Here, the protein small-molecule ligand validation tool Twilight is updated to include peptide ligands. (i) The primary technical reasons and potential human factors leading to problems in ligand structure models are presented; (ii) a new method used to score peptide-ligand models is presented; (iii) a few instructive and specific examples, including an electron-density-based analysis of peptide-ligand structures that do not contain any ligands, are discussed in detail; (iv) means to avoid such mistakes and the implications for database integrity are discussed and (v) some suggestions as to how journal editors could help to expunge errors from the Protein Data Bank are provided.

  8. Antimicrobial Peptides from Marine Proteobacteria

    PubMed Central

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-01-01

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

  9. Antiviral active peptide from oyster

    NASA Astrophysics Data System (ADS)

    Zeng, Mingyong; Cui, Wenxuan; Zhao, Yuanhui; Liu, Zunying; Dong, Shiyuan; Guo, Yao

    2008-08-01

    An active peptide against herpes virus was isolated from the enzymic hydrolysate of oyster ( Crassostrea gigas) and purified with the definite direction hydrolysis technique in the order of alcalase and bromelin. The hydrolysate was fractioned into four ranges of molecular weight (>10 kDa, 10 5 kDa, 5 1 kDa and <1 kDa) using ultrafiltration membranes and dialysis. The fraction of 10 5 kDa was purified using consecutive chromatographic methods including DEAE Sephadex A-25 column, Sephadex G-25 column, and high performance liquid chromatogram (HPLC) by activity-guided isolation. The antiviral effect of the obtained peptide on herpetic virus was investigated in Vero cells by observing cytopathic effect (CPE). The result shows that the peptide has high inhibitory activity on herpetic virus.

  10. Antimicrobial Peptide Production and Purification.

    PubMed

    Suda, Srinivas; Field, Des; Barron, Niall

    2017-01-01

    Antimicrobial peptides (AMPs) are natural defense compounds which are synthesized as ribosomal gene-encoded pre-peptides and produced by all living organisms. AMPs are small peptides, usually cationic and typically have hydrophobic residues which interact with cell membranes and have either a narrow or broad spectrum of biological activity. AMPs are isolated from the natural host or heterologously expressed in other hosts such as Escherichia coli. The proto-typical lantibiotic Nisin is a widely used AMP that is produced by the food-grade organism Lactococcus lactis. Although AMP production and purification procedures require optimization for individual AMPs, the Nisin production and purification protocol outlined in this chapter can be easily applied with minor modifications for the production and purification of other lantibiotics or AMPs. While Nisin is produced and secreted into the supernatant, steps to recover Nisin from both cell-free supernatant and cell pellet are outlined in detail.

  11. Membrane Perturbation Induced by Interfacially Adsorbed Peptides

    PubMed Central

    Zemel, Assaf; Ben-Shaul, Avinoam; May, Sylvio

    2004-01-01

    The structural and energetic characteristics of the interaction between interfacially adsorbed (partially inserted) α-helical, amphipathic peptides and the lipid bilayer substrate are studied using a molecular level theory of lipid chain packing in membranes. The peptides are modeled as “amphipathic cylinders” characterized by a well-defined polar angle. Assuming two-dimensional nematic order of the adsorbed peptides, the membrane perturbation free energy is evaluated using a cell-like model; the peptide axes are parallel to the membrane plane. The elastic and interfacial contributions to the perturbation free energy of the “peptide-dressed” membrane are evaluated as a function of: the peptide penetration depth into the bilayer's hydrophobic core, the membrane thickness, the polar angle, and the lipid/peptide ratio. The structural properties calculated include the shape and extent of the distorted (stretched and bent) lipid chains surrounding the adsorbed peptide, and their orientational (C-H) bond order parameter profiles. The changes in bond order parameters attendant upon peptide adsorption are in good agreement with magnetic resonance measurements. Also consistent with experiment, our model predicts that peptide adsorption results in membrane thinning. Our calculations reveal pronounced, membrane-mediated, attractive interactions between the adsorbed peptides, suggesting a possible mechanism for lateral aggregation of membrane-bound peptides. As a special case of interest, we have also investigated completely hydrophobic peptides, for which we find a strong energetic preference for the transmembrane (inserted) orientation over the horizontal (adsorbed) orientation. PMID:15189858

  12. Novel formulations for antimicrobial peptides.

    PubMed

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2014-10-09

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy.

  13. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  14. Peptides and the new endocrinology

    NASA Astrophysics Data System (ADS)

    Schwyzer, Robert

    1982-01-01

    The discovery of regulatory peptides common to the nervous and the endocrine systems (brain, gut, and skin) has brought about a revolution in our concepts of endocrinology and neurology. We are beginning to understand some of the complex interrelationships between soma and psyche that might, someday, be important for an integrated treatment of diseases. Examples of the actions of certain peptides in the periphery and in the central nervous system are given, and their biosynthesis and molecular anatomy as carriers for information are discussed.

  15. Biodiscovery of Aluminum Binding Peptides

    DTIC Science & Technology

    2013-08-01

    et al., "Biomimetic synthesis and patterning of silver nanoparticles ," Nat. Mater. 1(3), 169-172 (2002). [5] Van Dorst, B., et al., "Phage display...34Sequestration of zinc oxide by fimbrial designer chelators," Appl. Environ. Microbiol. 66(1), 10-14 (2000). [26] Hnilova, M., et al., "Peptide-directed co...biomaterial synthesis . Peptides have been developed that bind to a variety of inorganic materials, including metals1-6, oxides7, 8, alloys9, metal salts10

  16. An enhancer peptide for membrane-disrupting antimicrobial peptides

    PubMed Central

    2010-01-01

    Background NP4P is a synthetic peptide derived from a natural, non-antimicrobial peptide fragment (pro-region of nematode cecropin P4) by substitution of all acidic amino acid residues with amides (i.e., Glu → Gln, and Asp → Asn). Results In the presence of NP4P, some membrane-disrupting antimicrobial peptides (ASABF-α, polymyxin B, and nisin) killed microbes at lower concentration (e.g., 10 times lower minimum bactericidal concentration for ASABF-α against Staphylococcus aureus), whereas NP4P itself was not bactericidal and did not interfere with bacterial growth at ≤ 300 μg/mL. In contrast, the activities of antimicrobial agents with a distinct mode of action (indolicidin, ampicillin, kanamycin, and enrofloxacin) were unaffected. Although the membrane-disrupting activity of NP4P was slight or undetectable, ASABF-α permeabilized S. aureus membranes with enhanced efficacy in the presence of NP4P. Conclusions NP4P selectively enhanced the bactericidal activities of membrane-disrupting antimicrobial peptides by increasing the efficacy of membrane disruption against the cytoplasmic membrane. PMID:20152058

  17. Vasoactive intestinal peptide and electrical activity influence neuronal survival

    SciTech Connect

    Brenneman, D.E.; Eiden, L.E.

    1986-02-01

    Blockage of electrical activity in dissociated spinal cord cultures results in a significant loss of neurons during a critical period in development. Decreases in neuronal cell numbers and SVI-labeled tetanus toxin fixation produced by electrical blockage with tetrodotoxin (TTX) were prevented by addition of vasoactive intestinal peptide (VIP) to the nutrient medium. The most effective concentration of VIP was 0.1 nM. At higher concentrations, the survival-enhancing effect of VIP on TTX-treated cultures was attenuated. Addition of the peptide alone had no significant effect on neuronal cell counts or tetanus toxin fixation. With the same experimental conditions, two closely related peptides,more » PHI-27 (peptide, histidyl-isoleucine amide) and secretin, were found not to increase the number of neurons in TTX-treated cultures. Interference with VIP action by VIP antiserum resulted in neuronal losses that were not significantly different from those observed after TTX treatment. These data indicate that under conditions of electrical blockade a neurotrophic action of VIP on neuronal survival can be demonstrated.« less

  18. Metal stabilization of collagen and de novo designed mimetic peptides

    PubMed Central

    Parmar, Avanish S.; Xu, Fei; Pike, Douglas H.; Belure, Sandeep V.; Hasan, Nida F.; Drzewiecki, Kathryn E.; Shreiber, David I.; Nanda, Vikas

    2017-01-01

    We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix. PMID:26225466

  19. Metal Stabilization of Collagen and de Novo Designed Mimetic Peptides.

    PubMed

    Parmar, Avanish S; Xu, Fei; Pike, Douglas H; Belure, Sandeep V; Hasan, Nida F; Drzewiecki, Kathryn E; Shreiber, David I; Nanda, Vikas

    2015-08-18

    We explore the design of metal binding sites to modulate triple-helix stability of collagen and collagen-mimetic peptides. Globular proteins commonly utilize metals to connect tertiary structural elements that are well separated in sequence, constraining structure and enhancing stability. It is more challenging to engineer structural metals into fibrous protein scaffolds, which lack the extensive tertiary contacts seen in globular proteins. In the collagen triple helix, the structural adjacency of the carboxy-termini of the three chains makes this region an attractive target for introducing metal binding sites. We engineered His3 sites based on structural modeling constraints into a series of designed homotrimeric and heterotrimeric peptides, assessing the capacity of metal binding to improve stability and in the case of heterotrimers, affect specificity of assembly. Notable enhancements in stability for both homo- and heteromeric systems were observed upon addition of zinc(II) and several other metal ions only when all three histidine ligands were present. Metal binding affinities were consistent with the expected Irving-Williams series for imidazole. Unlike other metals tested, copper(II) also bound to peptides lacking histidine ligands. Acetylation of the peptide N-termini prevented copper binding, indicating proline backbone amide metal-coordination at this site. Copper similarly stabilized animal extracted Type I collagen in a metal-specific fashion, highlighting the potential importance of metal homeostasis within the extracellular matrix.

  20. C-peptide and Central Nervous System Complications in Diabetes

    PubMed Central

    Li, Zhen-guo

    2004-01-01

    Substantial evidence collected from clinical data and experimental studies has indicated that CNS is not spared from diabetes complications. Impairments in CNS function are well documented in both type 1 and type 2 diabetic patients as well as in various animal models of diabetes, in terms of alterations in cognition, neuropsychology, neurobehavior, electrophysiology, structure, neurochemistry and apoptotic activities. These data suggest that primary diabetic encephalopathy exists as a definable diabetic complication. The mechanisms underlying this CNS complication are not clear. Experimental studies have suggested that neuronal apoptosis may play an important role in neuronal loss and impaired cognitive function. In diabetes multiple factors are responsible for neuronal apoptosis, such as a perturbed IGF system, hyperglycemia and the aging process itself. Recent data suggest that insulin/C-peptide deficiency may exert an eminent role. Administration of C-peptide partially corrects the perturbed IGF system in the brain and prevents neuronal apoptosis in hippocampus of type 1 diabetes. In neuroblastoma SH-SY5Y cells C-peptide provides a dose-dependent stimulation on cell proliferation and an anti-apoptotic effect as well. These studies provide a basis for administration of C-peptide as a potentially effective therapy for type 1 diabetes. PMID:15198373

  1. E-Peptides Control Bioavailability of IGF-1

    PubMed Central

    Piszczek, Agnieszka; Perlas, Emarald; Winn, Nadine; Nastasi, Tommaso; Rosenthal, Nadia

    2012-01-01

    Insulin-like growth factor 1 (IGF-1) is a potent cytoprotective growth factor that has attracted considerable attention as a promising therapeutic agent. Transgenic over-expression of IGF-1 propeptides facilitates protection and repair in a broad range of tissues, although transgenic mice over-expressing IGF-1 propeptides display little or no increase in IGF-1 serum levels, even with high levels of transgene expression. IGF-1 propeptides are encoded by multiple alternatively spliced transcripts including C-terminal extension (E) peptides, which are highly positively charged. In the present study, we use decellularized mouse tissue to show that the E-peptides facilitate in vitro binding of murine IGF-1 to the extracellular matrix (ECM) with varying affinities. This property is independent of IGF-1, since proteins consisting of the E-peptides fused to relaxin, a related member of the insulin superfamily, bound equally avidly to decellularized ECM. Thus, the E-peptides control IGF-1 bioavailability by preventing systemic circulation, offering a potentially powerful way to tether IGF-1 and other therapeutic proteins to the site of synthesis and/or administration. PMID:23251442

  2. Streptavidin-binding peptides and uses thereof

    NASA Technical Reports Server (NTRS)

    Wilson, David S. (Inventor); Szostak, Jack W. (Inventor); Keefe, Anthony D. (Inventor)

    2005-01-01

    The invention provides peptides with high affinity for streptavidin. These peptides may be expressed as part of fusion proteins to facilitate the detection, quantitation, and purification of proteins of interest.

  3. Streptavidin-binding peptides and uses thereof

    NASA Technical Reports Server (NTRS)

    Szostak, Jack W. (Inventor); Keefe, Anthony D. (Inventor); Wilson, David S. (Inventor)

    2006-01-01

    The invention provides peptides with high affinity for streptavidin. These peptides may be expressed as part of fusion proteins to facilitate the detection, quantitation, and purification of proteins of interest.

  4. Boosting production yield of biomedical peptides

    NASA Technical Reports Server (NTRS)

    Manatt, S. L.

    1978-01-01

    Nuclear magnetic resonance (NMR) technique is employed to monitor synthesis of biomedical peptides. Application of NMR technique may improve production yields of insulin, ACTH, and growth hormones, as well as other synthesized biomedical peptides.

  5. Identification of tissue-specific targeting peptide

    NASA Astrophysics Data System (ADS)

    Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

    2012-11-01

    Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

  6. Investigating Endogenous Peptides and Peptidases using Peptidomics

    PubMed Central

    Tinoco, Arthur D.; Saghatelian, Alan

    2012-01-01

    Rather than simply being protein degradation products, peptides have proven to be important bioactive molecules. Bioactive peptides act as hormones, neurotransmitters and antimicrobial agents in vivo. The dysregulation of bioactive peptide signaling is also known to be involved in disease, and targeting peptide hormone pathways has been successful strategy in the development of novel therapeutics. The importance of bioactive peptides in biology has spurred research to elucidate the function and regulation of these molecules. Classical methods for peptide analysis have relied on targeted immunoassays, but certain scientific questions necessitated a broader and more detailed view of the peptidome–all the peptides in a cell, tissue or organism. In this review we discuss how peptidomics has emerged to fill this need through the application of advanced liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that provide unique insights into peptide activity and regulation. PMID:21786763

  7. Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers.

    PubMed

    Ahmed, Marya

    2017-10-24

    Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.

  8. Definition of agonists and design of antagonists for alloreactive T cell clones using synthetic peptide libraries.

    PubMed

    de Koster, H S; Vermeulen, C J; Hiemstra, H S; Amons, R; Drijfhout, J W; Koning, F

    1999-04-01

    Alloreactive T cells form an important barrier for organ transplantation. To reduce the risk of rejection patients are given immunosuppressive drugs, which increase the chance of infection and the incidence of malignancies. It has been shown that a large proportion of alloreactive T cells specifically recognize peptides present in the groove of the allogeneic MHC molecule. This implies that it might be possible to modulate the alloresponse by peptides with antagonistic properties, thus preventing rejection without the side effects of general immunosuppression. Peptide antagonists can be designed on the basis of the original agonist, yet for alloreactive T cells these agonists are usually unknown. In this study we have used a dedicated synthetic peptide library to identify agonists for HLA-DR3-specific alloreactive T cell clones. Based on these agonists, altered peptide ligands (APL) were designed. Three APL could antagonize an alloreactive T cell clone in its response against the library-derived agonist as well as in its response against the original allodeterminant, HLA-DR3. This demonstrates that peptide libraries can be used to design antagonists for alloreactive T cells without knowledge about the nature of the actual allostimulatory peptide. Since the most potent agonists are selected, this strategy permits detection of potent antagonists. The results, however, also suggest that the degree of peptide dependency of alloreactive T cell clones may dictate whether a peptide antagonist can be found for such clones. Whether peptide antagonists will be valuable in the development of donor-patient-specific immunosuppression may therefore depend on the specificity of the in vivo-generated alloreactive T cells.

  9. Treatment of Oral Multispecies Biofilms by an Anti-Biofilm Peptide.

    PubMed

    Wang, Zhejun; de la Fuente-Núñez, Cesar; Shen, Ya; Haapasalo, Markus; Hancock, Robert E W

    2015-01-01

    Human oral biofilms are multispecies microbial communities that exhibit high resistance to antimicrobial agents. Dental plaque gives rise to highly prevalent and costly biofilm-related oral infections, which lead to caries or other types of oral infections. We investigated the ability of the recently identified anti-biofilm peptide 1018 to induce killing of bacterial cells present within oral multispecies biofilms. At 10 μg/ml (6.5 μM), peptide 1018 was able to significantly (p<0.05) prevent biofilm formation over 3 days. The activity of the peptide on preformed biofilms was found to be concentration-dependent since more than 60% of the total plaque biofilm cell population was killed by 10 μg/ml of peptide 1018 in 3 days, while at 5 μg/ml 50% of cells were dead and at 1 μg/ml the peptide triggered cell death in around 30% of the total bacterial population, as revealed by confocal microscopy. The presence of saliva did not affect peptide activity, since no statistically significant difference was found in the ability of peptide 1018 to kill oral biofilms using either saliva coated and non-saliva coated hydroxyapatite surfaces. Scanning electron microscopy experiments indicated that peptide 1018 induced cell lysis in plaque biofilms. Furthermore, combined treatment using peptide 1018 and chlorhexidine (CHX) increased the anti-biofilm activity of each compound compared to when these were used alone, resulting in >50% of the biofilm being killed and >35% being dispersed in only 3 minutes. Peptide 1018 may potentially be used by itself or in combination with CHX as a non-toxic and effective anti-biofilm agent for plaque disinfection in clinical dentistry.

  10. Diverse CLE peptides from cyst nematode species

    USDA-ARS?s Scientific Manuscript database

    Plant CLAVATA3/ESR (CLE)-like peptides play diverse roles in plant growth and development including maintenance of the stem cell population in the root meristem. Small secreted peptides sharing similarity to plant CLE signaling peptides have been isolated from several cyst nematode species including...

  11. Tissue-specific effects of peptides.

    PubMed

    Khavinson, V K

    2001-08-01

    Synthetic peptides (cytogens) Cortagen, Epithalon, Livagen, and Vilon stimulated the growth of explants from rat brain cortex, subcortical structures, liver, and thymus, respectively, in organotypic cultures. These peptides produced tissue-specific effects: they stimulated the growth of explants from tissues, whose cytomedins (peptide complexes) were used for chemical synthesis.

  12. Toxins and antimicrobial peptides: interactions with membranes

    NASA Astrophysics Data System (ADS)

    Schlamadinger, Diana E.; Gable, Jonathan E.; Kim, Judy E.

    2009-08-01

    The innate immunity to pathogenic invasion of organisms in the plant and animal kingdoms relies upon cationic antimicrobial peptides (AMPs) as the first line of defense. In addition to these natural peptide antibiotics, similar cationic peptides, such as the bee venom toxin melittin, act as nonspecific toxins. Molecular details of AMP and peptide toxin action are not known, but the universal function of these peptides to disrupt cell membranes of pathogenic bacteria (AMPs) or a diverse set of eukaryotes and prokaryotes (melittin) is widely accepted. Here, we have utilized spectroscopic techniques to elucidate peptide-membrane interactions of alpha-helical human and mouse AMPs of the cathelicidin family as well as the peptide toxin melittin. The activity of these natural peptides and their engineered analogs was studied on eukaryotic and prokaryotic membrane mimics consisting of <200-nm bilayer vesicles composed of anionic and neutral lipids as well as cholesterol. Vesicle disruption, or peptide potency, was monitored with a sensitive fluorescence leakage assay. Detailed molecular information on peptidemembrane interactions and peptide structure was further gained through vibrational spectroscopy combined with circular dichroism. Finally, steady-state fluorescence experiments yielded insight into the local environment of native or engineered tryptophan residues in melittin and human cathelicidin embedded in bilayer vesicles. Collectively, our results provide clues to the functional structures of the engineered and toxic peptides and may impact the design of synthetic antibiotic peptides that can be used against the growing number of antibiotic-resistant pathogens.

  13. Identification of multifunctional peptides from human milk.

    PubMed

    Mandal, Santi M; Bharti, Rashmi; Porto, William F; Gauri, Samiran S; Mandal, Mahitosh; Franco, Octavio L; Ghosh, Ananta K

    2014-06-01

    Pharmaceutical industries have renewed interest in screening multifunctional bioactive peptides as a marketable product in health care applications. In this context, several animal and plant peptides with potential bioactivity have been reported. Milk proteins and peptides have received much attention as a source of health-enhancing components to be incorporated into nutraceuticals and functional foods. By using this source, 24 peptides have been fractionated and purified from human milk using RP-HPLC. Multifunctional roles including antimicrobial, antioxidant and growth stimulating activity have been evaluated in all 24 fractions. Nevertheless, only four fractions show multiple combined activities among them. Using a proteomic approach, two of these four peptides have been identified as lactoferrin derived peptide and kappa casein short chain peptide. Lactoferrin derived peptide (f8) is arginine-rich and kappa casein derived (f12) peptide is proline-rich. Both peptides (f8 and f12) showed antimicrobial activities against both Gram-positive and Gram-negative bacteria. Fraction 8 (f8) exhibits growth stimulating activity in 3T3 cell line and f12 shows higher free radical scavenging activity in comparison to other fractions. Finally, both peptides were in silico evaluated and some insights into their mechanism of action were provided. Thus, results indicate that these identified peptides have multiple biological activities which are valuable for the quick development of the neonate and may be considered as potential biotechnological products for nutraceutical industry. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants

    PubMed Central

    Yazici, Hilal; O'Neill, Mary B.; Kacar, Turgay; Wilson, Brandon R.; Oren, E. Emre; Sarikaya, Mehmet; Tamerler, Candan

    2016-01-01

    Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property. PMID:26795060

  15. Engineered Chimeric Peptides as Antimicrobial Surface Coating Agents toward Infection-Free Implants.

    PubMed

    Yazici, Hilal; O'Neill, Mary B; Kacar, Turgay; Wilson, Brandon R; Oren, E Emre; Sarikaya, Mehmet; Tamerler, Candan

    2016-03-02

    Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.

  16. Insect Peptides - Perspectives in Human Diseases Treatment.

    PubMed

    Chowanski, Szymon; Adamski, Zbigniew; Lubawy, Jan; Marciniak, Pawel; Pacholska-Bogalska, Joanna; Slocinska, Malgorzata; Spochacz, Marta; Szymczak, Monika; Urbanski, Arkadiusz; Walkowiak-Nowicka, Karolina; Rosinski, Grzegorz

    2017-01-01

    Insects are the largest and the most widely distributed group of animals in the world. Their diversity is a source of incredible variety of different mechanisms of life processes regulation. There are many agents that regulate immunology, reproduction, growth and development or metabolism. Hence, it seems that insects may be a source of numerous substances useful in human diseases treatment. Especially important in the regulation of insect physiology are peptides, like neuropeptides, peptide hormones or antimicrobial peptides. There are two main aspects where they can be helpful, 1) Peptides isolated from insects may become potential drugs in therapy of different diseases, 2) A lot of insect peptide hormones show structural or functional homology to mammalian peptide hormones and the comparative studies may give a new look on human disorders. In our review we focused on three group of insect derived peptides: 1) immune-active peptides, 2) peptide hormones and 3) peptides present in venoms. In our review we try to show the considerable potential of insect peptides in searching for new solutions for mammalian diseases treatment. We summarise the knowledge about properties of insect peptides against different virulent agents, anti-inflammatory or anti-nociceptive properties as well as compare insect and mammalian/vertebrate peptide endocrine system to indicate usefulness of knowledge about insect peptide hormones in drug design. The field of possible using of insect delivered peptide to therapy of various human diseases is still not sufficiently explored. Undoubtedly, more attention should be paid to insects due to searching new drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  17. A peptide N-terminal protection strategy for comprehensive glycoproteome analysis using hydrazide chemistry based method

    PubMed Central

    Huang, Junfeng; Qin, Hongqiang; Sun, Zhen; Huang, Guang; Mao, Jiawei; Cheng, Kai; Zhang, Zhang; Wan, Hao; Yao, Yating; Dong, Jing; Zhu, Jun; Wang, Fangjun; Ye, Mingliang; Zou, Hanfa

    2015-01-01

    Enrichment of glycopeptides by hydrazide chemistry (HC) is a popular method for glycoproteomics analysis. However, possible side reactions of peptide backbones during the glycan oxidation in this method have not been comprehensively studied. Here, we developed a proteomics approach to locate such side reactions and found several types of the side reactions that could seriously compromise the performance of glycoproteomics analysis. Particularly, the HC method failed to identify N-terminal Ser/Thr glycopeptides because the oxidation of vicinal amino alcohol on these peptides generates aldehyde groups and after they are covalently coupled to HC beads, these peptides cannot be released by PNGase F for identification. To overcome this drawback, we apply a peptide N-terminal protection strategy in which primary amine groups on peptides are chemically blocked via dimethyl labeling, thus the vicinal amino alcohols on peptide N-termini are eliminated. Our results showed that this strategy successfully prevented the oxidation of peptide N-termini and significantly improved the coverage of glycoproteome. PMID:25959593

  18. Mechanism by which DHA inhibits the aggregation of KLVFFA peptides: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Zhou, Hong; Liu, Shengtang; Shao, Qiwen; Ma, Dongfang; Yang, Zaixing; Zhou, Ruhong

    2018-03-01

    Docosahexaenoic acid (DHA) is one of the omega-3 polyunsaturated fatty acids, which has shown promising applications in lowering Aβ peptide neurotoxicity in vitro by preventing aggregation of Aβ peptides and relieving accumulation of Aβ fibrils. Unfortunately, the underlying molecular mechanisms of how DHA interferes with the aggregation of Aβ peptides remain largely enigmatic. Herein, aggregation behaviors of amyloid-β(Aβ)16-21 peptides (KLVFFA) with or without the presence of a DHA molecule were comparatively studied using extensive all-atom molecular dynamics simulations. We found that DHA could effectively suppress the aggregation of KLVFFA peptides by redirecting peptides to unstructured oligomers. The highly hydrophobic and flexible nature of DHA made it randomly but tightly entangled with Leu-17, Phe-19, and Phe-20 residues to form unstructured but stable complexes. These lower-ordered unstructured oligomers could eventually pass through energy barriers to form ordered β-sheet structures through large conformational fluctuations. This study depicts a microscopic picture for understanding the role and mechanism of DHA in inhibition of aggregation of Aβ peptides, which is generally believed as one of the important pathogenic mechanisms of Alzheimer's disease.

  19. RAId_DbS: Peptide Identification using Database Searches with Realistic Statistics

    PubMed Central

    Alves, Gelio; Ogurtsov, Aleksey Y; Yu, Yi-Kuo

    2007-01-01

    Background The key to mass-spectrometry-based proteomics is peptide identification. A major challenge in peptide identification is to obtain realistic E-values when assigning statistical significance to candidate peptides. Results Using a simple scoring scheme, we propose a database search method with theoretically characterized statistics. Taking into account possible skewness in the random variable distribution and the effect of finite sampling, we provide a theoretical derivation for the tail of the score distribution. For every experimental spectrum examined, we collect the scores of peptides in the database, and find good agreement between the collected score statistics and our theoretical distribution. Using Student's t-tests, we quantify the degree of agreement between the theoretical distribution and the score statistics collected. The T-tests may be used to measure the reliability of reported statistics. When combined with reported P-value for a peptide hit using a score distribution model, this new measure prevents exaggerated statistics. Another feature of RAId_DbS is its capability of detecting multiple co-eluted peptides. The peptide identification performance and statistical accuracy of RAId_DbS are assessed and compared with several other search tools. The executables and data related to RAId_DbS are freely available upon request. PMID:17961253

  20. Anti-Biofilm Activity of a Self-Aggregating Peptide against Streptococcus mutans

    PubMed Central

    Ansari, Juliana M.; Abraham, Nabil M.; Massaro, Jenna; Murphy, Kelsey; Smith-Carpenter, Jillian; Fikrig, Erol

    2017-01-01

    Streptococcus mutans is the primary agent of dental cavities, in large part due to its ability to adhere to teeth and create a molecular scaffold of glucan polysaccharides on the tooth surface. Disrupting the architecture of S. mutans biofilms could help undermine the establishment of biofilm communities that cause cavities and tooth decay. Here we present a synthetic peptide P1, derived from a tick antifreeze protein, which significantly reduces S. mutans biofilm formation. Incubating cells with this peptide decreased biofilm biomass by approximately 75% in both a crystal violet microplate assay and an in vitro tooth model using saliva-coated hydroxyapatite discs. Bacteria treated with peptide P1 formed irregular biofilms with disconnected aggregates of cells and exopolymeric matrix that readily detached from surfaces. Peptide P1 can bind directly to S. mutans cells but does not possess bactericidal activity. Anti-biofilm activity was correlated with peptide aggregation and β-sheet formation in solution, and alternative synthetic peptides of different lengths or charge distribution did not inhibit biofilms. This anti-biofilm peptide interferes with S. mutans biofilm formation and architecture, and may have future applications in preventing bacterial buildup on teeth. PMID:28392782

  1. Prospects in the use of aptamers for characterizing the structure and stability of bioactive proteins and peptides in food.

    PubMed

    Agyei, Dominic; Acquah, Caleb; Tan, Kei Xian; Hii, Hieng Kok; Rajendran, Subin R C K; Udenigwe, Chibuike C; Danquah, Michael K

    2018-01-01

    Food-derived bioactive proteins and peptides have gained acceptance among researchers, food manufacturers and consumers as health-enhancing functional food components that also serve as natural alternatives for disease prevention and/or management. Bioactivity in food proteins and peptides is determined by their conformations and binding characteristics, which in turn depend on their primary and secondary structures. To maintain their bioactivities, the molecular integrity of bioactive peptides must remain intact, and this warrants the study of peptide form and structure, ideally with robust, highly specific and sensitive techniques. Short single-stranded nucleic acids (i.e. aptamers) are known to have high affinity for cognate targets such as proteins and peptides. Aptamers can be produced cost-effectively and chemically derivatized to increase their stability and shelf life. Their improved binding characteristics and minimal modification of the target molecular signature suggests their suitability for real-time detection of conformational changes in both proteins and peptides. This review discusses the developmental progress of systematic evolution of ligands by exponential enrichment (SELEX), an iterative technology for generating cost-effective aptamers with low dissociation constants (K d ) for monitoring the form and structure of bioactive proteins and peptides. The review also presents case studies of this technique in monitoring the structural stability of bioactive peptide formulations to encourage applications in functional foods. The challenges and potential of aptamers in this research field are also discussed. Graphical abstract Advancing bioactive proteins and peptide functionality via aptameric ligands.

  2. Biomimetic graphene sensors: functionalizing graphene with peptides

    NASA Astrophysics Data System (ADS)

    Ishigami, Masa; Nyon Kim, Sang; Naik, Rajesh; Tatulian, Suren A.; Katoch, Jyoti

    2012-02-01

    Non-covalent biomimetic functionalization of graphene using peptides is one of more promising methods for producing novel sensors with high sensitivity and selectivity. Here we combine atomic force microscopy, Raman spectroscopy, and attenuated total reflection Fourier transform infrared spectroscopy to investigate peptide binding to graphene and graphite. We choose to study a dodecamer peptide identified with phage display to possess affinities for graphite and we find that the peptide forms a complex mesh-like structure upon adsorption on graphene. Moreover, optical spectroscopy reveals that the peptide binds non-covalently to graphene and possesses an optical signature of an ?-helical conformation on graphene.

  3. Isoelectric focusing of proteins and peptides

    NASA Technical Reports Server (NTRS)

    Egen, N.

    1979-01-01

    Egg-white solution was chosen as the reference solution in order to assess the effects of operational parameters (voltage, flow rate, ampholine pH range and concentration, and protein concentration) of the RIEF apparatus on protein resolution. Topics of discussion include: (1) comparison of RIEF apparatus to conventional IEF techniques (column and PAG) with respect to resolution and throughput; (2) peptide and protein separation (AHF, Thymosin - Fraction 5, vasoactive peptide, L-asparaginase and ACP); and (3) detection of peptides - dansyl derivatives of amino acids and peptides, post-focusing fluorescent labeling of amino acids, peptides and proteins, and ampholine extraction from focused gels.

  4. Remineralization of initial enamel caries in vitro using a novel peptide based on amelogenin

    NASA Astrophysics Data System (ADS)

    Li, Danxue; Lv, Xueping; Tu, Huanxin; Zhou, Xuedong; Yu, Haiyang; Zhang, Linglin

    2015-09-01

    Dental caries is the most common oral disease with high incidence, widely spread and can seriously affect the health of oral cavity and the whole body. Current caries prevention measures such as fluoride treatment, antimicrobial agents, and traditional Chinese herbal, have limitations to some extent. Here we design and synthesize a novel peptide based on the amelogenin, and assess its ability to promote the remineralization of initial enamel caries lesions. We used enamel blocks to form initial lesions, and then subjected to 12-day pH cycling in the presence of peptide, NaF and HEPES buffer. Enamel treated with peptide or NaF had shallower, narrower lesions, thicker remineralized surfaces and less mineral loss than enamel treated with HEPES. This peptide can promote the remineralization of initial enamel caries and inhibit the progress of caries. It is a promising anti-caries agent with various research prospects and practical application value.

  5. A Bioinformatics Workflow for Variant Peptide Detection in Shotgun Proteomics*

    PubMed Central

    Li, Jing; Su, Zengliu; Ma, Ze-Qiang; Slebos, Robbert J. C.; Halvey, Patrick; Tabb, David L.; Liebler, Daniel C.; Pao, William; Zhang, Bing

    2011-01-01

    Shotgun proteomics data analysis usually relies on database search. However, commonly used protein sequence databases do not contain information on protein variants and thus prevent variant peptides and proteins from been identified. Including known coding variations into protein sequence databases could help alleviate this problem. Based on our recently published human Cancer Proteome Variation Database, we have created a protein sequence database that comprehensively annotates thousands of cancer-related coding variants collected in the Cancer Proteome Variation Database as well as noncancer-specific ones from the Single Nucleotide Polymorphism Database (dbSNP). Using this database, we then developed a data analysis workflow for variant peptide identification in shotgun proteomics. The high risk of false positive variant identifications was addressed by a modified false discovery rate estimation method. Analysis of colorectal cancer cell lines SW480, RKO, and HCT-116 revealed a total of 81 peptides that contain either noncancer-specific or cancer-related variations. Twenty-three out of 26 variants randomly selected from the 81 were confirmed by genomic sequencing. We further applied the workflow on data sets from three individual colorectal tumor specimens. A total of 204 distinct variant peptides were detected, and five carried known cancer-related mutations. Each individual showed a specific pattern of cancer-related mutations, suggesting potential use of this type of information for personalized medicine. Compatibility of the workflow has been tested with four popular database search engines including Sequest, Mascot, X!Tandem, and MyriMatch. In summary, we have developed a workflow that effectively uses existing genomic data to enable variant peptide detection in proteomics. PMID:21389108

  6. Entrapment of Aβ1-40 peptide in unstructured aggregates

    NASA Astrophysics Data System (ADS)

    Corsale, C.; Carrotta, R.; Mangione, M. R.; Vilasi, S.; Provenzano, A.; Cavallaro, G.; Bulone, D.; San Biagio, P. L.

    2012-06-01

    Recognizing the complexity of the fibrillogenesis process provides a solid ground for the development of therapeutic strategies aimed at preventing or inhibiting protein-protein aggregation. Under this perspective, it is meaningful to identify the possible aggregation pathways and their relative products. We found that Aβ-peptide dissolved in a pH 7.4 solution at small peptide concentration and low ionic strength forms globular aggregates without typical amyloid β-conformation. ThT binding kinetics was used to monitor aggregate formation. Circular dichroism spectroscopy, AFM imaging, static and dynamic light scattering were used for structural and morphological characterization of the aggregates. They appear stable or at least metastable with respect to fiber growth, therefore appearing as an incidental product in the pathway of fibrillogenesis.

  7. Hypothesis driven development of new adjuvants: short peptides as immunomodulators.

    PubMed

    Dong, Jessica C; Kobinger, Gary P

    2013-04-01

    To date, vaccinations have been one of the key strategies in the prevention and protection against infectious pathogens. Traditional vaccines have well-known limitations such as safety and efficacy issues, which consequently deems it inappropriate for particular populations and may not be an effective strategy against all pathogens. This evidence highlights the need to develop more efficacious vaccination regiments. Higher levels of protection can be achieved by the addition of immunostimulating adjuvants. Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects. Hypothesis driven development of adjuvants is needed to achieve a more specific and directed immune response required for optimal and safe vaccine-induced immune protection. An example of such hypothesis driven development includes the use of short immunomodulating peptides as adjuvants. These peptides have the ability to influence the immune response and can be extrapolated for adjuvant use, but requires further investigation.

  8. Detoxification depot for beta-amyloid peptides.

    PubMed

    Sundaram, Ranjini K; Kasinathan, Chinnaswamy; Stein, Stanley; Sundaram, Pazhani

    2008-02-01

    Alzheimer's Disease (AD) is caused by the deposition of insoluble and toxic amyloid peptides (Abeta) in the brain leading to memory loss and other associated neurodegenerative symptoms. To date there is limited treatment options and strategies for treating AD. Studies have shown that clearance of the amyloid plaques from the brain and thus from the blood could be effective in stopping and or delaying the progression of the disease. Small peptides derived from the Abeta-42 sequence, in particular KLVFF, have shown to be effective binders of Abeta peptides and thus could be useful in delaying progression of the disease. We have taken advantage of this property by generating the retro-inverso (RI) version of this peptide, ffvlk, in different formats. We are presenting a new detox gel system using poly ethylene glycol (PEG), polymerized and cross linked with the RI peptides. We hypothesize that detox gel incorporating RI peptides will act like a 'sink' to capture the Abeta peptides from the surrounding environment. We tested these detox gels for their ability to capture biotinylated Abeta-42 peptides in vitro. The results showed that the detox gels bound Abeta-42 peptides effectively and irreversibly. Gels incorporating the tetramer RI peptide exhibited maximum binding capacity. The detox gel could be a potential candidate for treatment strategies to deplete the brain of toxic amyloid peptides.

  9. Inhibition of pressure-activated cancer cell adhesion by FAK-derived peptides

    PubMed Central

    Zeng, Bixi; Devadoss, Dinesh; Wang, Shouye; Vomhof-DeKrey, Emilie E.; Kuhn, Leslie A.; Basson, Marc D.

    2017-01-01

    Forces within the surgical milieu or circulation activate cancer cell adhesion and potentiate metastasis through signaling requiring FAK-Akt1 interaction. Impeding FAK-Akt1 interaction might inhibit perioperative tumor dissemination, facilitating curative cancer surgery without global FAK or AKT inhibitor toxicity. Serial truncation and structurally designed mutants of FAK identified a seven amino acid, short helical structure within FAK that effectively competes with Akt1-FAK interaction. Adenoviral overexpression of this FAK-derived peptide inhibited pressure-induced FAK phosphorylation and AKT-FAK coimmunoprecipitation in human SW620 colon cancer cells briefly exposed to 15mmHg increased pressure, consistent with laparoscopic or post-surgical pressures. Adenoviral FAK-derived peptide expression prevented pressure-activation of SW620 adhesion not only to collagen-I-coated plates but also to murine surgical wounds. A scrambled peptide did not. Finally, we modeled operative shedding of tumor cells before irrigation and closure by transient cancer cell adhesion to murine surgical wounds before irrigation and closure. Thirty minute preincubation of SW620 cells at 15mmHg increased pressure impaired subsequent tumor free survival in mice exposed to cells expressing the scrambled peptide. The FAK-derived sequence prevented this. These results suggest that blocking FAK-Akt1 interaction may prevent perioperative tumor dissemination and that analogs or mimics of this 7 amino acid FAK-derived peptide could impair metastasis. PMID:29228673

  10. Chemopreventive role of food-derived proteins and peptides: A review.

    PubMed

    Hernández-Ledesma, Blanca; Hsieh, Chia-Chien

    2017-07-24

    Cancer is one of the leading causes of mortality and disability worldwide. Although great advances in cancer treatments such as chemotherapy, surgery, and radiation are currently being achieved, their application is associated with numerous and expensive adverse side effects. Epidemiological evidence has demonstrated that the consumption of certain foods potentially prevents up to 35% of cancer cases. Bioactive components are ubiquitous in nature, also in dietary food, providing an essential link in health maintenance, promotion, and prevention of chronic diseases, such as cancer. Development of bioactive proteins and peptides is a current and innovative strategy for cancer prevention/cure. A growing body of anticancer protein and peptides from natural sources has shown the ability to reduce tumor progression through multiple mechanisms including apoptotic, antiproliferative, antiangiogenic, and immunomodulatory activities. This review is focused on proteins and peptides from different food sources including plants, milk, egg, and marine organisms in which chemopreventive properties have been demonstrated. Other aspects such as mechanism of action, bioavailability, and identification and characterization of food-derived peptides by advance separated technologies are also included. This review highlights the potential application of food-derived peptides as functional food ingredients and pharmaceutical candidates in the auxiliary therapy of cancer.

  11. Dendrimer-conjugated peptide vaccine enhances clearance of Chlamydia trachomatis genital infection.

    PubMed

    Ganda, Ingrid S; Zhong, Qian; Hali, Mirabela; Albuquerque, Ricardo L C; Padilha, Francine F; da Rocha, Sandro R P; Whittum-Hudson, Judith A

    2017-07-15

    Peptide-based vaccines have emerged in recent years as promising candidates in the prevention of infectious diseases. However, there are many challenges to maintaining in vivo peptide stability and enhancement of peptide immunogenicity to generate protective immunity which enhances clearance of infections. Here, a dendrimer-based carrier system is proposed for peptide-based vaccine delivery, and shows its anti-microbial feasibility in a mouse model of Chlamydia trachomatis. Chlamydiae are the most prevalent sexually transmitted bacteria worldwide, and also the causal agent of trachoma, the leading cause of preventable infectious blindness. In spite of the prevalence of this infectious agent and the many previous vaccine-related studies, there is no vaccine commercially available. The carrier system proposed consists of generation 4, hydroxyl-terminated, polyamidoamine (PAMAM) dendrimers (G4OH), to which a peptide mimic of a chlamydial glycolipid antigen-Peptide 4 (Pep4, AFPQFRSATLLL) was conjugated through an ester bond. The ester bond between G4OH and Pep4 is expected to break down mainly in the intracellular environment for antigen presentation. Pep4 conjugated to dendrimer induced Chlamydia-specific serum antibodies after subcutaneous immunizations. Further, this new vaccine formulation significantly protected immunized animals from vaginal challenge with infectious Chlamydia trachomatis, and it reduced infectious loads and tissue (genital tract) damage. Pep4 conjugated to G4OH or only mixed with peptide provided enhanced protection compared to Pep4 and adjuvant (i.e. alum), suggesting a potential adjuvant effect of the PAMAM dendrimer. Combined, these results demonstrate that hydroxyl-terminated PAMAM dendrimer is a promising polymeric nanocarrier platform for the delivery of peptide vaccines and this approach has potential to be expanded to other infectious intracellular bacteria and viruses of public health significance. Copyright © 2017 Elsevier B.V. All

  12. Antimicrobial peptide coatings for hydroxyapatite: electrostatic and covalent attachment of antimicrobial peptides to surfaces.

    PubMed

    Townsend, Leigh; Williams, Richard L; Anuforom, Olachi; Berwick, Matthew R; Halstead, Fenella; Hughes, Erik; Stamboulis, Artemis; Oppenheim, Beryl; Gough, Julie; Grover, Liam; Scott, Robert A H; Webber, Mark; Peacock, Anna F A; Belli, Antonio; Logan, Ann; de Cogan, Felicity

    2017-01-01

    The interface between implanted devices and their host tissue is complex and is often optimized for maximal integration and cell adhesion. However, this also gives a surface suitable for bacterial colonization. We have developed a novel method of modifying the surface at the material-tissue interface with an antimicrobial peptide (AMP) coating to allow cell attachment while inhibiting bacterial colonization. The technology reported here is a dual AMP coating. The dual coating consists of AMPs covalently bonded to the hydroxyapatite surface, followed by deposition of electrostatically bound AMPs. The dual approach gives an efficacious coating which is stable for over 12 months and can prevent colonization of the surface by both Gram-positive and Gram-negative bacteria. © 2017 The Author(s).

  13. Antimicrobial peptide coatings for hydroxyapatite: electrostatic and covalent attachment of antimicrobial peptides to surfaces

    PubMed Central

    Townsend, Leigh; Williams, Richard L.; Anuforom, Olachi; Berwick, Matthew R.; Halstead, Fenella; Hughes, Erik; Stamboulis, Artemis; Oppenheim, Beryl; Gough, Julie; Grover, Liam; Scott, Robert A. H.; Webber, Mark; Peacock, Anna F. A.; Belli, Antonio; Logan, Ann

    2017-01-01

    The interface between implanted devices and their host tissue is complex and is often optimized for maximal integration and cell adhesion. However, this also gives a surface suitable for bacterial colonization. We have developed a novel method of modifying the surface at the material–tissue interface with an antimicrobial peptide (AMP) coating to allow cell attachment while inhibiting bacterial colonization. The technology reported here is a dual AMP coating. The dual coating consists of AMPs covalently bonded to the hydroxyapatite surface, followed by deposition of electrostatically bound AMPs. The dual approach gives an efficacious coating which is stable for over 12 months and can prevent colonization of the surface by both Gram-positive and Gram-negative bacteria. PMID:28077764

  14. Suicide Prevention

    MedlinePlus

    ... help high schools, school districts, and their partners design and implement strategies to prevent suicide and promote behavioral health among their students. Now Is The Time—Prevention and Early Intervention ...

  15. Taylor Dispersion Analysis as a promising tool for assessment of peptide-peptide interactions.

    PubMed

    Høgstedt, Ulrich B; Schwach, Grégoire; van de Weert, Marco; Østergaard, Jesper

    2016-10-10

    Protein-protein and peptide-peptide (self-)interactions are of key importance in understanding the physiochemical behavior of proteins and peptides in solution. However, due to the small size of peptide molecules, characterization of these interactions is more challenging than for proteins. In this work, we show that protein-protein and peptide-peptide interactions can advantageously be investigated by measurement of the diffusion coefficient using Taylor Dispersion Analysis. Through comparison to Dynamic Light Scattering it was shown that Taylor Dispersion Analysis is well suited for the characterization of protein-protein interactions of solutions of α-lactalbumin and human serum albumin. The peptide-peptide interactions of three selected peptides were then investigated in a concentration range spanning from 0.5mg/ml up to 80mg/ml using Taylor Dispersion Analysis. The peptide-peptide interactions determination indicated that multibody interactions significantly affect the PPIs at concentration levels above 25mg/ml for the two charged peptides. Relative viscosity measurements, performed using the capillary based setup applied for Taylor Dispersion Analysis, showed that the viscosity of the peptide solutions increased with concentration. Our results indicate that a viscosity difference between run buffer and sample in Taylor Dispersion Analysis may result in overestimation of the measured diffusion coefficient. Thus, Taylor Dispersion Analysis provides a practical, but as yet primarily qualitative, approach to assessment of the colloidal stability of both peptide and protein formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Rape prevention

    MedlinePlus

    Date rape - prevention; Sexual assault - prevention ... Centers for Disease Control and Prevention website. Sexual assault and abuse and STDs. In: 2015 sexually transmitted diseases treatment guidelines 2015. www.cdc.gov/std/tg2015/sexual-assault.htm . Updated June 4, ...

  17. SPR4-peptide Alters Bone Metabolism of Normal and HYP Mice

    PubMed Central

    Zelenchuk, Lesya V; Hedge, Anne-Marie; Rowe, Peter S N

    2015-01-01

    Context ASARM-peptides are substrates and ligands for PHEX, the gene responsible for X-linked hypophosphatemic rickets (HYP). PHEX binds to the DMP1-ASARM-motif to form a trimeric-complex with α5β3-integrin on the osteocyte surface and this suppresses FGF23 expression. ASARM-peptide disruption of this complex increases FGF23 expression. We used a 4.2 kDa peptide (SPR4) that binds to ASARM-peptide and ASARM-motif to study DMP1-PHEX interactions and to assess SPR4 for treating inherited hypophosphatemic rickets. Design Subcutaneously transplanted osmotic pumps were used to infuse SPR4-peptide or vehicle into wild-type mice (WT) and HYP-mice for 4 weeks. Results Asymmetrically distributed mineralization defects occurred with WT-SPR4 femurs. Specifically, SPR4 induced negative effects on trabecular bone and increased bone volume and mineralization in cortical-bone. Markedly increased sclerostin and reduced active β-catenin occurred with HYP mice. SPR4-infusion suppressed sclerostin and increased active β-catenin in WT and HYP mice and improved HYP-mice trabecular mineralization defects but not cortical mineralization defects. Conclusions SPR4-peptide has bimodal activity and acts by: (1) preventing DMP1 binding to PHEX and (2) sequestering an inhibitor of DMP1-PHEX binding, ASARM-peptide. In PHEX defective HYP-mice the second pathway predominates. Although SPR4-peptide improved trabecular calcification defects, decreased sclerostin and increased active β-catenin it did not correct HYP-mice cortical mineralization defects on a normal phosphate diet. Thus, for inherited hypophosphatemic rickets patients on a normal phosphate diet, SPR4-peptide is not a useful therapeutic. PMID:25460577

  18. Peptide stabilized amphotericin B nanodisks

    PubMed Central

    Tufteland, Megan; Pesavento, Joseph B.; Bermingham, Rachelle L.; Hoeprich, Paul D.; Ryan, Robert O.

    2007-01-01

    Nanometer scale apolipoprotein A-I stabilized phospholipid disk complexes (nanodisks; ND) have been formulated with the polyene antibiotic amphotericin B (AMB). The present studies were designed to evaluate if a peptide can substitute for the function of the apolipoprotein component of ND with respect to particle formation and stability. An 18-residue synthetic amphipathic α-helical peptide, termed 4F (Ac-D-W-F-K-A-F-Y-D-K-V-A-E-K-F-K-E-A-F-NH2), solubilized vesicles comprised of egg phosphatidylcholine (egg PC), dipentadecanoyl PC or dimyristoylphosphatidylcholine (DMPC) at rates greater than or equal to solubilization rates observed with human apolipoprotein A-I (apoA-I; 243 amino acids). Characterization studies revealed that interaction with DMPC induced a near doubling of 4F tryptophan fluorescence emission quantum yield (excitation 280 nm) and a ~7 nm blue shift in emission wavelength maximum. Inclusion of AMB in the vesicle substrate resulted in formation of 4F AMB-ND. Spectra of AMB containing particles revealed the antibiotic is a highly effective quencher of 4F tryptophan fluorescence emission, giving rise to a Ksv = 7.7 × 104. Negative stain electron microscopy revealed that AMB-ND prepared with 4F possessed a disk shaped morphology similar to ND prepared without AMB or prepared with apoA-I. In yeast and pathogenic fungi growth inhibition assays, 4F AMB-ND was as effective as apoA-I AMB-ND. The data indicate that AMB-ND generated using an amphipathic peptide in lieu of apoA-I form a discrete population of particles that possess potent biological activity. Given their intrinsic versatility, peptides may be preferred for scale up and clinical application of AMB-ND. PMID:17293004

  19. Characterisation and evaluation of antiviral recombinant peptides based on the heptad repeat regions of NDV and IBV fusion glycoproteins

    SciTech Connect

    Wang Xiaojia, E-mail: wangxj@cau.edu.cn; Li Chuangen; Chi Xiaojing

    Mixed virus infections can cause livestock losses that are more devastating than those caused by single virus infections. Newcastle disease virus (NDV) and infectious bronchitis virus (IBV), serious threats to the poultry industry, can give rise to complex mixed infections that hinder diagnosis and prevention. In this study, we show that newly designed peptides, which are based on the heptad repeat (HR) region of the fusion glycoproteins from NDV and IBV, have more potent antiviral activity than the mother HR peptides. Plaque formation and chicken embryo infectivity assays confirmed these results. The novel peptides completely inhibited single virus infections andmore » mixed infections caused by NDV and IBV. Furthermore, we assessed cell toxicity and possible targets for the peptides, thereby strengthening the notion that HR2 is an attractive site for therapeutic intervention. These results suggest the possibility of designing a relatively broad-spectrum class of antiviral peptides that can reduce the effects of mixed-infections.« less

  20. Coffee, hunger, and peptide YY.

    PubMed

    Greenberg, James A; Geliebter, Allan

    2012-06-01

    There is evidence from several empirical studies suggesting that coffee may help people control body weight. Our objective was to assess the effects of caffeine, caffeinated coffee, and decaffeinated coffee, both alone and in combination with 75 g of glucose, on perceived hunger and satiety and related peptides. We conducted a placebo-controlled single-blinded randomized 4-way crossover trial. Eleven healthy male volunteers (mean age, 23.5 ± 5.7 years; mean BMI, 23.6 ± 4.2 kg/m(2)) ingested 1 of 3 test beverages (caffeine in water, caffeinated coffee, or decaffeinated coffee) or placebo (water), and 60 minutes later they ingested the glucose. Eight times during each laboratory visit, hunger and satiety were assessed by visual analog scales, and blood samples were drawn to measure 3 endogenous peptides associated with hunger and satiety: ghrelin, peptide YY (PYY), and leptin. Compared to placebo, decaffeinated coffee yielded significantly lower hunger during the whole 180-minute study period and higher plasma PYY for the first 90 minutes (p < 0.05). Caffeine in water had no effects on hunger or PYY. Caffeinated coffee showed a pattern between that of decaffeinated coffee and caffeine in water. These findings suggest that one or more noncaffeine ingredients in coffee may have the potential to decrease body weight. Glucose ingestion did not change the effects of the beverages. Our randomized human trial showed that decaffeinated coffee can acutely decrease hunger and increase the satiety hormone PYY.

  1. Biopharmaceuticals: From peptide to drug

    NASA Astrophysics Data System (ADS)

    Hannappel, Margarete

    2017-08-01

    Biologics are therapeutic proteins or peptides that are produced by means of biological processes within living organisms and cells. They are highly specific molecules and play a crucial role as therapeutics for the treatment of severe and chronic diseases (e.g. cancer, rheumatoid arthritis, diabetes, autoimmune disorders). The development of new biologics and biologics-based drugs gains more and more importance in the fight against various diseases. A short overview on biotherapeutical drug development is given. Cone snails are a large group of poisonous, predatory sea snails with more than 700 species. They use a very powerful venom which rapidly inactivates and paralyzes their prey. Most bioactive venom components are small peptides (conotoxins, conopeptides) which are precisely directed towards a specific target (e.g. ion channel, receptors). Due to their small size, their precision and speed of action, naturally occurring cone snail venom peptides represent an attractive source for the identification and design of novel biological drug entities. The Jagna cone snail project is an encouraging initiative to map the ecological variety of cone snails around the island of Bohol (Philippines) and to conserve the biological information for potential future application.

  2. Chemical methods for peptide and protein production.

    PubMed

    Chandrudu, Saranya; Simerska, Pavla; Toth, Istvan

    2013-04-12

    Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.

  3. Stability of peptide drugs in the colon.

    PubMed

    Wang, Jie; Yadav, Vipul; Smart, Alice L; Tajiri, Shinichiro; Basit, Abdul W

    2015-10-12

    This study was the first to investigate the colonic stability of 17 peptide molecules (insulin, calcitonin, glucagon, secretin, somatostatin, desmopressin, oxytocin, Arg-vasopressin, octreotide, ciclosporin, leuprolide, nafarelin, buserelin, histrelin, [D-Ser(4)]-gonadorelin, deslorelin, and goserelin) in a model of the large intestine using mixed human faecal bacteria. Of these, the larger peptides - insulin, calcitonin, somatostatin, glucagon and secretin - were metabolized rapidly, with complete degradation observed within 5 min. In contrast, a number of the smaller peptides - Arg-vasopressin, desmopressin, oxytocin, gonadorelin, goserelin, buserelin, leuprolide, nafarelin and deslorelin - degraded more slowly, while octreotide, histrelin and ciclosporin were seen to be more stable as compared to the other small peptides under the same conditions. Peptide degradation rate was directly correlated to peptide lipophilicity (logP); those peptides with a higher logP were more stable in the colonic model (R(2)=0.94). In the absence of human faecal bacteria, all peptides were stable. This study highlights the impact of the colonic environment - in particular, the gut microbiota - on the metabolism of peptide drugs, and identifies potential peptide candidates for drug delivery to the colon. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Human Antimicrobial Peptides and Proteins

    PubMed Central

    Wang, Guangshun

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to

  5. Isolation of low-molecular albumins of 2S fraction from soybean (Glycine max (L.) Merrill).

    PubMed

    Galbas, Mariola; Porzucek, Filip; Woźniak, Anna; Słomski, Ryszard; Selwet, Marek

    2013-01-01

    Numerous studies have shown that consumption of soybean products decrease the risk of cancers in humans. Experiments at the molecular level have demonstrated that in most cases proteins and peptides are responsible for the anticancer properties of soybeen. Special attention should be paid to lunasin - a peptide described for the first time 16 years ago. Due to its structure it causes i.a., inhibition of cancer cell proliferation. A novel procedure for the isolation and purification of low-molecular-mass 2S soybean albumin protein is described in the present paper. A fraction of four peptides one of them corresponding to molecular mass and isoelectric point characteristic for lunasin. The obtained peptides decreased on the rate of HeLa cell proliferation.

  6. Methionine peptide formation under primordial earth conditions.

    PubMed

    Li, Feng; Fitz, Daniel; Fraser, Donald G; Rode, Bernd M

    2008-01-01

    According to recent research on the origin of life it seems more and more likely that amino acids and peptides were among the first biomolecules formed on earth and that a peptide/protein world was thus a key starting point in evolution towards life. Salt-induced Peptide Formation (SIPF) has repeatedly been shown to be the most universal and plausible peptide-forming reaction currently known under prebiotic conditions and forms peptides from amino acids with the help of copper ions and sodium chloride. In this paper we present experimental results for salt-induced peptide formation from methionine. This is the first time that a sulphur-containing amino acid was investigated in this reaction. The possible catalytic effects of glycine and L-histidine in this reaction were also investigated and a possible distinction between the L- and D-forms of methionine was studied as well.

  7. Toward structure prediction of cyclic peptides.

    PubMed

    Yu, Hongtao; Lin, Yu-Shan

    2015-02-14

    Cyclic peptides are a promising class of molecules that can be used to target specific protein-protein interactions. A computational method to accurately predict their structures would substantially advance the development of cyclic peptides as modulators of protein-protein interactions. Here, we develop a computational method that integrates bias-exchange metadynamics simulations, a Boltzmann reweighting scheme, dihedral principal component analysis and a modified density peak-based cluster analysis to provide a converged structural description for cyclic peptides. Using this method, we evaluate the performance of a number of popular protein force fields on a model cyclic peptide. All the tested force fields seem to over-stabilize the α-helix and PPII/β regions in the Ramachandran plot, commonly populated by linear peptides and proteins. Our findings suggest that re-parameterization of a force field that well describes the full Ramachandran plot is necessary to accurately model cyclic peptides.

  8. Potent peptidic fusion inhibitors of influenza virus

    SciTech Connect

    Kadam, Rameshwar U.; Juraszek, Jarek; Brandenburg, Boerries

    Influenza therapeutics with new targets and mechanisms of action are urgently needed to combat potential pandemics, emerging viruses, and constantly mutating strains in circulation. We report here on the design and structural characterization of potent peptidic inhibitors of influenza hemagglutinin. The peptide design was based on complementarity-determining region loops of human broadly neutralizing antibodies against the hemagglutinin (FI6v3 and CR9114). The optimized peptides exhibit nanomolar affinity and neutralization against influenza A group 1 viruses, including the 2009 H1N1 pandemic and avian H5N1 strains. The peptide inhibitors bind to the highly conserved stem epitope and block the low pH–induced conformational rearrangementsmore » associated with membrane fusion. These peptidic compounds and their advantageous biological properties should accelerate the development of new small molecule– and peptide-based therapeutics against influenza virus.« less

  9. Hevein-Like Antimicrobial Peptides of Plants.

    PubMed

    Slavokhotova, A A; Shelenkov, A A; Andreev, Ya A; Odintsova, T I

    2017-12-01

    Plant antimicrobial peptides represent one of the evolutionarily oldest innate immunity components providing the first line of host defense to pathogen attacks. This review is dedicated to a small, currently actively studied family of hevein-like peptides that can be found in various monocot and dicot plants. The review thoroughly describes all known peptides belonging to this family including data on their structures, functions, and antimicrobial activity. The main features allowing to assign these peptides to a separate family are given, and the specific characteristics of each peptide are described. Further, the mode of action for hevein-like peptides, their role in plant immune system, and the applications of these molecules in biotechnology and medicine are considered.

  10. Natriuretic peptides: Diagnostic and therapeutic use

    PubMed Central

    Pandit, Kaushik; Mukhopadhyay, Pradip; Ghosh, Sujoy; Chowdhury, Subhankar

    2011-01-01

    Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones. PMID:22145138

  11. Synthesis of peptide .alpha.-thioesters

    DOEpatents

    Camarero, Julio A [Livermore, CA; Mitchell, Alexander R [Livermore, CA; De Yoreo, James J [Clayton, CA

    2008-08-19

    Disclosed herein is a new method for the solid phase peptide synthesis (SPPS) of C-terminal peptide .alpha. thioesters using Fmoc/t-Bu chemistry. This method is based on the use of an aryl hydrazine linker, which is totally stable to conditions required for Fmoc-SPPS. When the peptide synthesis has been completed, activation of the linker is achieved by mild oxidation. The oxidation step converts the acyl-hydrazine group into a highly reactive acyl-diazene intermediate which reacts with an .alpha.-amino acid alkylthioester (H-AA-SR) to yield the corresponding peptide .alpha.-thioester in good yield. A variety of peptide thioesters, cyclic peptides and a fully functional Src homology 3 (SH3) protein domain have been successfully prepared.

  12. Peptides having reduced toxicity that stimulate cholesterol efflux

    SciTech Connect

    Bielicki, John K.; Johansson, Jan; Danho, Waleed

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABCA1 that parallels that of full-length apolipoproteins. Further, the peptides of the invention have little or no toxicity when administered at therapeutic and higher doses. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  13. Treatment of Oral Biofilms by a D-Enantiomeric Peptide.

    PubMed

    Zhang, Tian; Wang, Zhejun; Hancock, Robert E W; de la Fuente-Núñez, César; Haapasalo, Markus

    2016-01-01

    Almost all dental diseases are caused by biofilms that consist of multispecies communities. DJK-5, which is a short D-enantiomeric, protease-resistant peptide with broad-spectrum anti-biofilm activity, was tested for its effect on oral multispecies biofilms. Peptide DJK-5 at 10 μg/mL effectively prevented the growth of these microbes in culture media in a time-dependent manner. In addition to the prevention of growth, peptide DJK-5 completely killed both Streptococcus mutans and Enterococcus faecalis suspended from biofilms after 30 minutes of incubation in liquid culture media. DJK-5 also led to the effective killing of microbes in plaque biofilm. The proportion of bacterial cells killed by 10 μg/mL of DJK-5 was similar after 1 and 3 days, both exceeding 85%. DJK-5 was able to significantly prevent biofilm formation over 3 days (P = 0.000). After 72 hours of exposure, DJK-5 significantly reduced and almost completely prevented plaque biofilm production by more than 90% of biovolume compared to untreated controls (P = 0.000). The proportion of dead biofilm bacteria at the 10 μg/mL DJK-5 concentration was similar for 1- and 3-day-old biofilms, whereby >86% of the bacteria were killed. DJK-5 was also able to kill >79% and >85% of bacteria, respectively, after one-time and three brief treatments of 3-day-old biofilms. The combination of DJK-5 and chlorhexidine showed the best bacterial killing among all treatments, with ~83% and >88% of bacterial cells killed after 1 and 3 minutes, respectively. No significant difference was found in the percentage of biofilm killing amongst three donor plaque samples after DJK-5 treatment. In particular, DJK-5 showed strong performance in inhibiting biofilm development and eradicating pre-formed oral biofilms compared to L-enantiomeric peptide 1018. DJK-5 was very effective against oral biofilms when used alone or combined with chlorhexidine, and may be a promising agent for use in oral anti-biofilm strategies in the future.

  14. Use of galerina marginata genes and proteins for peptide production

    SciTech Connect

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  15. Use of Galerina marginata genes and proteins for peptide production

    SciTech Connect

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  16. Use of Galerina marginata genes and proteins for peptide production

    DOEpatents

    Hallen-Adams, Heather E.; Scott-Craig, John S.; Walton, Jonathan D.; Luo, Hong

    2016-03-01

    The present invention relates to compositions and methods comprising genes and peptides associated with cyclic peptides and cyclic peptide production in mushrooms. In particular, the present invention relates to using genes and proteins from Galerina species encoding peptides specifically relating to amatoxins in addition to proteins involved with processing cyclic peptide toxins. In a preferred embodiment, the present invention also relates to methods for making small peptides and small cyclic peptides including peptides similar to amanitin. Further, the present inventions relate to providing kits for making small peptides.

  17. An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model.

    PubMed

    Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

    2015-10-01

    Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6-8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) was orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20 μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. An endostatin-derived peptide orally exerts anti-fibrotic activity in a murine pulmonary fibrosis model

    PubMed Central

    Nishimoto, Tetsuya; Mlakar, Logan; Takihara, Takahisa; Feghali-Bostwick, Carol

    2016-01-01

    Objective Pulmonary fibrosis causes high morbidity and mortality in affected individuals. Recently, we showed that parenteral or intratracheal administration of a peptide derived from endostatin, called E4, prevents and ameliorates fibrosis using different models of dermal and pulmonary disease. No marketed orally delivered peptide drugs are currently available for progressive pulmonary fibrosis; however oral delivery of drugs is the preferred route for treating most chronic diseases. Thus, we investigated whether oral administration of E4 peptide exerted anti-fibrotic activity in a murine pulmonary fibrosis model. Methods Bleomycin (1.2mU/g body weight) was intratracheally administrated to male 6–8-week-old C57BL/6J mice. E4 peptide (20, 10, 5, and 1 μg/mouse) or scrambled control peptide (20 μg/mouse) were orally administered on the same day as bleomycin. In some experiments, E4 peptide (10 and 5 μg/mouse) was orally administered three times on days 0, 3, and 6 post-bleomycin treatment. Lungs were harvested on day 21 for histological analysis and hydroxyproline assay. Results Histological analysis and hydroxyproline assay revealed that bleomycin successfully induced pulmonary fibrosis, and that 20μg of oral E4 peptide ameliorated the fibrosis. The lower doses of E4 peptide (10, 5, and 1 μg) were insufficient to exert anti-fibrotic activity when given as a single dose. Multiple doses of E4 peptide efficiently exerted anti-fibrotic activity even at lower doses. Conclusion E4 peptide shows oral bioavailability and exerts anti-fibrotic activity in a bleomycin-induced pulmonary fibrosis model. We suggest that E4 peptide is a novel oral drug for fibroproliferative disorders. PMID:26315492

  19. Current scenario of peptide-based drugs: the key roles of cationic antitumor and antiviral peptides

    PubMed Central

    Mulder, Kelly C. L.; Lima, Loiane A.; Miranda, Vivian J.; Dias, Simoni C.; Franco, Octávio L.

    2013-01-01

    Cationic antimicrobial peptides (AMPs) and host defense peptides (HDPs) show vast potential as peptide-based drugs. Great effort has been made in order to exploit their mechanisms of action, aiming to identify their targets as well as to enhance their activity and bioavailability. In this review, we will focus on both naturally occurring and designed antiviral and antitumor cationic peptides, including those here called promiscuous, in which multiple targets are associated with a single peptide structure. Emphasis will be given to their biochemical features, selectivity against extra targets, and molecular mechanisms. Peptides which possess antitumor activity against different cancer cell lines will be discussed, as well as peptides which inhibit virus replication, focusing on their applications for human health, animal health and agriculture, and their potential as new therapeutic drugs. Moreover, the current scenario for production and the use of nanotechnology as delivery tool for both classes of cationic peptides, as well as the perspectives on improving them is considered. PMID:24198814

  20. Therapeutic peptides for cancer therapy. Part I - peptide inhibitors of signal transduction cascades.

    PubMed

    Bidwell, Gene L; Raucher, Drazen

    2009-10-01

    Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that inhibit signal transduction cascades are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Given our current knowledge of protein sequences, structures and interaction interfaces, therapeutic peptides that inhibit interactions of interest are easily designed. These peptides are advantageous because they are highly specific for the interaction of interest, and they are much more easily developed than small molecule inhibitors of the same interactions. The main hurdle to application of peptides for cancer therapy is their poor pharmacokinetic and biodistribution parameters. Therefore, successful development of peptide delivery vectors could potentially make possible the use of this new and very promising class of anticancer agents.

  1. A novel chimeric peptide with antimicrobial activity.

    PubMed

    Alaybeyoglu, Begum; Akbulut, Berna Sariyar; Ozkirimli, Elif

    2015-04-01

    Beta-lactamase-mediated bacterial drug resistance exacerbates the prognosis of infectious diseases, which are sometimes treated with co-administration of beta-lactam type antibiotics and beta-lactamase inhibitors. Antimicrobial peptides are promising broad-spectrum alternatives to conventional antibiotics in this era of evolving bacterial resistance. Peptides based on the Ala46-Tyr51 beta-hairpin loop of beta-lactamase inhibitory protein (BLIP) have been previously shown to inhibit beta-lactamase. Here, our goal was to modify this peptide for improved beta-lactamase inhibition and cellular uptake. Motivated by the cell-penetrating pVEC sequence, which includes a hydrophobic stretch at its N-terminus, our approach involved the addition of LLIIL residues to the inhibitory peptide N-terminus to facilitate uptake. Activity measurements of the peptide based on the 45-53 loop of BLIP for enhanced inhibition verified that the peptide was a competitive beta-lactamase inhibitor with a K(i) value of 58 μM. Incubation of beta-lactam-resistant cells with peptide decreased the number of viable cells, while it had no effect on beta-lactamase-free cells, indicating that this peptide had antimicrobial activity via beta-lactamase inhibition. To elucidate the molecular mechanism by which this peptide moves across the membrane, steered molecular dynamics simulations were carried out. We propose that addition of hydrophobic residues to the N-terminus of the peptide affords a promising strategy in the design of novel antimicrobial peptides not only against beta-lactamase but also for other intracellular targets. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.

  2. Molecular specialization of breast vasculature: A breast-homing phage-displayed peptide binds to aminopeptidase P in breast vasculature

    NASA Astrophysics Data System (ADS)

    Essler, Markus; Ruoslahti, Erkki

    2002-02-01

    In vivo phage display identifies peptides that selectively home to the vasculature of individual organs, tissues, and tumors. Here we report the identification of a cyclic nonapeptide, CPGPEGAGC, which homes to normal breast tissue with a 100-fold selectivity over nontargeted phage. The homing of the phage is inhibited by its cognate synthetic peptide. Phage localization in tissue sections showed that the breast-homing phage binds to the blood vessels in the breast, but not in other tissues. The phage also bound to the vasculature of hyperplastic and malignant lesions in transgenic breast cancer mice. Expression cloning with a phage-displayed cDNA library yielded a phage that specifically bound to the breast-homing peptide. The cDNA insert was homologous to a fragment of aminopeptidase P. The homing peptide bound aminopeptidase P from malignant breast tissue in affinity chromatography. Antibodies against aminopeptidase P inhibited the in vitro binding of the phage-displayed cDNA to the peptide and the in vivo homing of phage carrying the peptide. These results indicate that aminopeptidase P is the receptor for the breast-homing peptide. This peptide may be useful in designing drugs for the prevention and treatment of breast cancer.

  3. Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications

    PubMed Central

    Zhang, Guolong; Sunkara, Lakshmi T.

    2014-01-01

    Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens. PMID:24583933

  4. Antimicrobial Peptides as Mediators of Innate Immunity in Teleosts

    PubMed Central

    Katzenback, Barbara A.

    2015-01-01

    Antimicrobial peptides (AMPs) have been identified throughout the metazoa suggesting their evolutionarily conserved nature and their presence in teleosts is no exception. AMPs are short (18–46 amino acids), usually cationic, amphipathic peptides. While AMPs are diverse in amino acid sequence, with no two AMPs being identical, they collectively appear to have conserved functions in the innate immunity of animals towards the pathogens they encounter in their environment. Fish AMPs are upregulated in response to pathogens and appear to have direct broad-spectrum antimicrobial activity towards both human and fish pathogens. However, an emerging role for AMPs as immunomodulatory molecules has become apparent—the ability of AMPs to activate the innate immune system sheds light onto the multifaceted capacity of these small peptides to combat pathogens through direct and indirect means. Herein, this review focuses on the role of teleost AMPs as modulators of the innate immune system and their regulation in response to pathogens or other exogenous molecules. The capacity to regulate AMP expression by exogenous factors may prove useful in modulating AMP expression in fish to prevent disease, particularly in aquaculture settings where crowded conditions and environmental stress pre-dispose these fish to infection. PMID:26426065

  5. Processing of mammalian preprogastrin-releasing peptide.

    PubMed

    Reeve, J R; Cuttitta, F; Vigna, S R; Shively, J E; Walsh, J H

    1988-01-01

    The processing of preprogastrin-releasing peptide in mammalian tissues and in cultured cells takes place at discrete sites (Figure 6). Signal peptidase cleaves away the signal peptide from the amino terminus of gastrin-releasing peptide. An exopeptidase activity may remove dipeptides from the amino terminus. The amidation site (not shown in Fig. 6; see Fig. 2) has the same general sequence (Gly-Lys-Lys) seen for other amidated peptides. Cleavage after single basic residues yields gene-related products from Form I or II preproGRP. A unique non-basic cleavage yields a gene-related product from Form III preproGRP. The processing that occurs to form GRP, GRP, and GRP gene-related peptides is shown in Figure 7. ProGRP is cleaved by a series of enzymes to form GRP with an amidated carboxyl-terminal methionine (indicated by an asterisk in Fig. 7). GRP is cleaved to form the decapeptide GRP. The carboxyl-terminal flanking peptides of all three mRNA translation products are cleaved to form several gastrin-releasing peptide gene-related products. Knowledge of the processing of gastrin-releasing peptide and its gene-related products will allow synthesis of duplicates of the stored forms of these peptides, which can then be used for biological testing.

  6. Novel Synthetic Antimicrobial Peptides against Streptococcus mutans▿

    PubMed Central

    He, Jian; Eckert, Randal; Pharm, Thanh; Simanian, Maurice D.; Hu, Chuhong; Yarbrough, Daniel K.; Qi, Fengxia; Anderson, Maxwell H.; Shi, Wenyuan

    2007-01-01

    Streptococcus mutans, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against S. mutans. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these “fusion” peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against S. mutans, several of which may be likely candidates for the development of anticaries agents. PMID:17296741

  7. Polycyclic Peptides: A New Type of Cavitand,

    DTIC Science & Technology

    PEPTIDES, MOLECULAR STRUCTURE, MOLECULES, SYNTHESIS, ETHERS, DEXTRINS , PROTEINS, AMINO ACIDS, RESIDUES, CROSSLINKING(CHEMISTRY), DIMERS, CESIUM, CARBON, OXYGEN, NITROGEN, CAVITIES, NUCLEAR MAGNETIC RESONANCE.

  8. (Lipo)polysaccharide interactions of antimicrobial peptides.

    PubMed

    Schmidtchen, Artur; Malmsten, Martin

    2015-07-01

    Due to rapidly increasing resistance development against conventional antibiotics, as well as problems associated with diseases either triggered or deteriorated by infection, antimicrobial and anti-inflammatory peptides have attracted considerable interest during the last few years. While there is an emerging understanding of the direct antimicrobial function of such peptides through bacterial membrane destabilization, the mechanisms of their anti-inflammatory function are less clear. We here summarize some recent results obtained from our own research on anti-inflammatory peptides, with focus on peptide-(lipo)polysaccharide interactions. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Milk derived bioactive peptides and their impact on human health - A review.

    PubMed

    Mohanty, D P; Mohapatra, S; Misra, S; Sahu, P S

    2016-09-01

    Milk-derived bioactive peptides have been identified as potential ingredients of health-promoting functional foods. These bioactive peptides are targeted at diet-related chronic diseases especially the non-communicable diseases viz., obesity, cardiovascular diseases and diabetes. Peptides derived from the milk of cow, goat, sheep, buffalo and camel exert multifunctional properties, including anti-microbial, immune modulatory, anti-oxidant, inhibitory effect on enzymes, anti-thrombotic, and antagonistic activities against various toxic agents. Majority of those regulate immunological, gastrointestinal, hormonal and neurological responses, thereby playing a vital role in the prevention of cancer, osteoporosis, hypertension and other disorders as discussed in this review. For the commercial production of such novel bioactive peptides large scale technologies based on membrane separation and ion exchange chromatography methods have been developed. Separation and identification of those peptides and their pharmacodynamic parameters are necessary to transfer their potent functional properties into food applications. The present review summarizes the preliminary classes of bioactive milk-derived peptides along with their physiological functions, general characteristics and potential applications in health-care.

  10. Peptides derived from tryptic hydrolysate of Bacillus subtilis culture suppress fungal spoilage of table grapes.

    PubMed

    Zhang, Bo; Wang, Jingnan; Ning, Shuqing; Yuan, Quan; Chen, Xiangning; Zhang, Yanyan; Fan, Junfeng

    2018-01-15

    This study confirmed the anti-fungal effect of trypsin-treated Bacillus subtilis culture (BC) (tryptic hydrolysate, TH) on mold growth on Kyoho grapes. We examined the anti-fungal activity of TH by identifying TH peptides and performing a computational docking analysis. TH was more potent than untreated BC in suppressing fungal growth on grapes. Specifically, TH maintained grape freshness by inhibiting respiration and rachis browning, maintaining firmness, and preventing weight loss. Thirty-six inhibitory peptides against β-1,3-glucan synthase (GS) were screened from 126 TH peptides identified through proteomic analysis. Among them, 13 peptides bound tightly to GS active pockets with lower binding energies than that of GppNHp. The most potent peptides, LFEIDEELNEK and FATSDLNDLYR, were synthesized, and further experiments showed that these peptides had a highly suppressive effect on GS activity and Aspergillus niger and Penicillium chrysogenum growth. Our results confirm that tryptic treatment is effective for improving the anti-fungal activity of BC. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Thioamide Substitution Selectively Modulates Proteolysis and Receptor Activity of Therapeutic Peptide Hormones.

    PubMed

    Chen, Xing; Mietlicki-Baase, Elizabeth G; Barrett, Taylor M; McGrath, Lauren E; Koch-Laskowski, Kieran; Ferrie, John J; Hayes, Matthew R; Petersson, E James

    2017-11-22

    Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution. In GLP-1 and GIP, a single thioamide near the scissile bond renders these peptides up to 750-fold more stable than the corresponding oxopeptides toward cleavage by dipeptidyl peptidase 4, the principal regulator of their in vivo stability. These stabilized analogues are nearly equipotent with their parent peptide in cyclic AMP activation assays, but the GLP-1 thiopeptides have much lower β-arrestin potency, making them novel agonists with altered signaling bias. Initial tests show that a thioamide GLP-1 analogue is biologically active in rats, with an in vivo potency for glycemic control surpassing that of native GLP-1. Taken together, these experiments demonstrate the potential for thioamides to modulate specific protein interactions to increase proteolytic stability or tune activation of different signaling pathways.

  12. Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus

    PubMed Central

    Dey, Sumanta; De, Antara; Nandy, Ashesh

    2016-01-01

    Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time. PMID:27279731

  13. Piracetam inhibits the lipid-destabilising effect of the amyloid peptide Abeta C-terminal fragment.

    PubMed

    Mingeot-Leclercq, Marie-Paule; Lins, Laurence; Bensliman, Mariam; Thomas, Annick; Van Bambeke, Françoise; Peuvot, Jacques; Schanck, André; Brasseur, Robert

    2003-01-10

    Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor protein (APP), implicated in the pathogenesis of Alzheimer's disease. The hypothesis that interactions between Abeta aggregates and neuronal membranes play an important role in toxicity has gained some acceptance. Previously, we showed that the C-terminal domain (e.g. amino acids 29-42) of Abeta induces membrane permeabilisation and fusion, an effect which is related to the appearance of non-bilayer structures. Conformational studies showed that this peptide has properties similar to those of the fusion peptide of viral proteins i.e. a tilted penetration into membranes. Since piracetam interacts with lipids and has beneficial effects on several symptoms of Alzheimer's disease, we investigated in model membranes the ability of piracetam to hinder the destabilising effect of the Abeta 29-42 peptide. Using fluorescence studies and 31P and 2H NMR spectroscopy, we have shown that piracetam was able to significantly decrease the fusogenic and destabilising effect of Abeta 29-42, in a concentration-dependent manner. While the peptide induced lipid disorganisation and subsequent negative curvature at the membrane-water interface, the conformational analysis showed that piracetam, when preincubated with lipids, coats the phospholipid headgroups. Calculations suggest that this prevents appearance of the peptide-induced curvature. In addition, insertion of molecules with an inverted cone shape, like piracetam, into the outer membrane leaflet should make the formation of such structures energetically less favourable and therefore decrease the likelihood of membrane fusion.

  14. Differences in signal peptide processing between GP3 glycoproteins of Arteriviridae.

    PubMed

    Zhang, Minze; Veit, Michael

    2018-04-01

    We reported previously that carbohydrate attachment to an overlapping glycosylation site adjacent to the signal peptide of GP3 from equine arteritis virus (EAV) prevents cleavage. Here we investigated whether this unusual processing scheme is a feature of GP3s of other Arteriviridae, which all contain a glycosylation site at a similar position. Expression of GP3 from type-1 and type-2 porcine reproductive and respiratory syndrome virus (PRRSV) and from lactate dehydrogenase-elevating virus (LDV) revealed that the first glycosylation site is used, but has no effect on signal peptide cleavage. Comparison of the SDS-PAGE mobility of deglycosylated GP3 from PRRSV and LDV with mutants having or not having a signal peptide showed that GP3´s signal peptide is cleaved. Swapping the signal peptides between GP3 of EAV and PRRSV revealed that the information for co-translational processing is not encoded in the signal peptide, but in the remaining part of GP3. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Functional characterization of a synthetic hydrophilic antifungal peptide derived from the marine snail Cenchritis muricatus.

    PubMed

    López-Abarrategui, Carlos; Alba, Annia; Silva, Osmar N; Reyes-Acosta, Osvaldo; Vasconcelos, Ilka M; Oliveira, Jose T A; Migliolo, Ludovico; Costa, Maysa P; Costa, Carolina R; Silva, Maria R R; Garay, Hilda E; Dias, Simoni C; Franco, Octávio L; Otero-González, Anselmo J

    2012-04-01

    Antimicrobial peptides have been found in mollusks and other sea animals. In this report, a crude extract of the marine snail Cenchritis muricatus was evaluated against human pathogens responsible for multiple deleterious effects and diseases. A peptide of 1485.26 Da was purified by reversed-phase HPLC and functionally characterized. This trypsinized peptide was sequenced by MS/MS technology, and a sequence (SRSELIVHQR), named Cm-p1 was recovered, chemically synthesized and functionally characterized. This peptide demonstrated the capacity to prevent the development of yeasts and filamentous fungi. Otherwise, Cm-p1 displayed no toxic effects against mammalian cells. Molecular modeling analyses showed that this peptide possible forms a single hydrophilic α-helix and the probable cationic residue involved in antifungal activity action is proposed. The data reported here demonstrate the importance of sea animals peptide discovery for biotechnological tools development that could be useful in solving human health and agribusiness problems. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Novel chimeric peptide with enhanced cell specificity and anti-inflammatory activity.

    PubMed

    Kim, Young-Min; Kim, Nam-Hong; Lee, Jong-Wan; Jang, Jin-Sun; Park, Yung-Hoon; Park, Seong-Cheol; Jang, Mi-Kyeong

    2015-07-31

    An antimicrobial peptide (AMP), Hn-Mc, was designed by combining the N-terminus of HPA3NT3 and the C-terminus of melittin. This chimeric AMP exhibited potent antibacterial activity with low minimal inhibitory concentrations (MICs), ranging from 1 to 2 μM against four drug-susceptible bacteria and ten drug-resistant bacteria. Moreover, the hemolysis and cytotoxicity was reduced significantly compared to those of the parent peptides, highlighting its high cell selectivity. The morphological changes in the giant unilamellar vesicles and bacterial cell surfaces caused by the Hn-Mc peptide suggested that it killed the microbial cells by damaging the membrane envelope. An in vivo study also demonstrated the antibacterial activity of the Hn-Mc peptide in a mouse model infected with drug-resistant bacteria. In addition, the chimeric peptide inhibited the expression of lipopolysaccharide (LPS)-induced cytokines in RAW 264.7 cells by preventing the interaction between LPS and Toll-like receptors. These results suggest that this chimeric peptide is an antimicrobial and anti-inflammatory candidate as a pharmaceutic agent. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Peptide reranking with protein-peptide correspondence and precursor peak intensity information.

    PubMed

    Yang, Chao; He, Zengyou; Yang, Can; Yu, Weichuan

    2012-01-01

    Searching tandem mass spectra against a protein database has been a mainstream method for peptide identification. Improving peptide identification results by ranking true Peptide-Spectrum Matches (PSMs) over their false counterparts leads to the development of various reranking algorithms. In peptide reranking, discriminative information is essential to distinguish true PSMs from false PSMs. Generally, most peptide reranking methods obtain discriminative information directly from database search scores or by training machine learning models. Information in the protein database and MS1 spectra (i.e., single stage MS spectra) is ignored. In this paper, we propose to use information in the protein database and MS1 spectra to rerank peptide identification results. To quantitatively analyze their effects to peptide reranking results, three peptide reranking methods are proposed: PPMRanker, PPIRanker, and MIRanker. PPMRanker only uses Protein-Peptide Map (PPM) information from the protein database, PPIRanker only uses Precursor Peak Intensity (PPI) information, and MIRanker employs both PPM information and PPI information. According to our experiments on a standard protein mixture data set, a human data set and a mouse data set, PPMRanker and MIRanker achieve better peptide reranking results than PetideProphet, PeptideProphet+NSP (number of sibling peptides) and a score regularization method SRPI. The source codes of PPMRanker, PPIRanker, and MIRanker, and all supplementary documents are available at our website: http://bioinformatics.ust.hk/pepreranking/. Alternatively, these documents can also be downloaded from: http://sourceforge.net/projects/pepreranking/.

  18. Chimeric peptides as implant functionalization agents for titanium alloy implants with antimicrobial properties.

    PubMed

    Yucesoy, Deniz T; Hnilova, Marketa; Boone, Kyle; Arnold, Paul M; Snead, Malcolm L; Tamerler, Candan

    2015-04-01

    Implant-associated infections can have severe effects on the longevity of implant devices and they also represent a major cause of implant failures. Treating these infections associated with implants by antibiotics is not always an effective strategy due to poor penetration rates of antibiotics into biofilms. Additionally, emerging antibiotic resistance poses serious concerns. There is an urge to develop effective antibacterial surfaces that prevent bacterial adhesion and proliferation. A novel class of bacterial therapeutic agents, known as antimicrobial peptides (AMP's), are receiving increasing attention as an unconventional option to treat septic infection, partly due to their capacity to stimulate innate immune responses and for the difficulty of microorganisms to develop resistance towards them. While host- and bacterial- cells compete in determining the ultimate fate of the implant, functionalization of implant surfaces with antimicrobial peptides can shift the balance and prevent implant infections. In the present study, we developed a novel chimeric peptide to functionalize the implant material surface. The chimeric peptide simultaneously presents two functionalities, with one domain binding to a titanium alloy implant surface through a titanium-binding domain while the other domain displays an antimicrobial property. This approach gains strength through control over the bio-material interfaces, a property built upon molecular recognition and self-assembly through a titanium alloy binding domain in the chimeric peptide. The efficiency of chimeric peptide both in-solution and absorbed onto titanium alloy surface was evaluated in vitro against three common human host infectious bacteria, S. mutans, S. epidermidis , and E. coli . In biological interactions such as occurs on implants, it is the surface and the interface that dictate the ultimate outcome. Controlling the implant surface by creating an interface composed chimeric peptides may therefore open up

  19. Functional selection of a type IV pili-binding peptide that specifically inhibits Salmonella Typhi adhesion to/invasion of human monocytic cells.

    PubMed

    Wu, Hong-Yan; Zhang, Xiao-Lian; Pan, Qin; Wu, Jianguo

    2005-11-01

    Salmonella enterica serovar Typhi (S. Typhi) is an important pathogen which infects humans exclusively and causes typhoid or enteric fever. Recently it has been discovered that type IVB pili, encoded by the S. Typhi pil operon located in the major pathogenicity island, may be important in the pathogenesis of epidemic enteric fever. To further investigate the roles of type IVB pili of S. Typhi, a 12-mer peptide (RQERSSLSKPVV), binding to the structural protein PilS of the type IVB pili of S. Typhi, was isolated with a ribosome display system. This peptide was designated as peptide R. We found that peptide R inhibited adhesion to/invasion of human monocytic THP-1 cells by piliated S. Typhi bacteria, but had no effects on nonpiliated S. Typhi bacteria. A random 12-mer peptide, of size and solubility equal to peptide R, served as a control on the specificity of peptide R. The specific interaction and binding equilibrium between the 12-mer peptide R and PilS protein was determined by isothermal titration calorimetry (ITC) and a binding constant Ka determined to be between 0.4 x 10(5) and 2.2 x 10(5)L mol(-1). Our findings suggest that the type IV pili-binding peptide R holds potential as an antibacterial peptide effective against S. Typhi infections, both in terms of prevention and therapeutic treatment. The data further provide insights into the understanding of the pathogenic roles of the type IVB pili of S. Typhi.

  20. Recombinant heat shock protein 70 functional peptide and alpha-fetoprotein epitope peptide vaccine elicits specific anti-tumor immunity.

    PubMed

    Wang, Xiao-Ping; Wang, Qiao-Xia; Lin, Huan-Ping; Xu, Bing; Zhao, Qian; Chen, Kun

    2016-11-01

    Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P. This novel peptide was administered into BALB/c mice to observe the effects. Quantification of AFP-specific CD8 + T cells that secrete IFN-γ in these mice via ELISPOT revealed the synergistic effects of HSP70-P/AFP-P with increased numbers of AFP-specific CD8 + T cells. Similarly, ELISA analysis showed increased granzyme B and perforin released by natural killer cells. Moreover, in vitro cytotoxic T-lymphocyte assays and in vivo tumor preventive experiments clearly showed the higher antitumor effects of HSP70-P/AFP-P against AFP-expressing tumors. These results show that treatment of BALB/c mice with HSP70-P/AFP-P induced stronger T-cells responses and improved protective immunity. Our data suggest that HSP70-P/AFP-P may be used as a therapeutic approach in the treatment of AFP-expressing cancers.

  1. Alternatives to antibiotics: bacteriocins, antimicrobial peptides and bacteriophages.

    PubMed

    Joerger, R D

    2003-04-01

    Bacteriocins, antimicrobial peptides, and bacteriophage have attracted attention as potential substitutes for, or as additions to, currently used antimicrobial compounds. This publication will review research on the potential application of these alternative antimicrobial agents to poultry production and processing. Bacteriocins are proteinaceous compounds of bacterial origin that are lethal to bacteria other than the producing strain. It is assumed that some of the bacteria in the intestinal tract produce bacteriocins as a means to achieve a competitive advantage, and bacteriocin-producing bacteria might be a desirable part of competitive exclusion preparations. Purified or partially purified bacteriocins could be used as preservatives or for the reduction or elimination of certain pathogens. Currently only nisin, produced by certain strains of Lactococcus lactis subsp. lactis, has regulatory approval for use in certain foods, and its use for poultry products has been studied extensively. Exploration of the application of antimicrobial peptides from sources other than bacteria to poultry has not yet commenced to a significant extent. Evidence for the ability of chickens to produce such antimicrobial peptides has been provided, and it is likely that these peptides play an important role in the defense against various pathogens. Bacteriophages have received renewed attention as possible agents against infecting bacteria. Evidence from several trials indicates that phage therapy can be effective under certain circumstances. Numerous obstacles for the use of phage as antimicrobials for poultry or poultry products remain. Chiefly among them are the narrow host range of many phages, the issue of phage resistance, and the possibility of phage-mediated transfer of genetic material to bacterial hosts. Regulatory issues and the high cost of producing such alternative antimicrobial agents are also factors that might prevent application of these agents in the near future.

  2. A paradigm shift: Cancer therapy with peptide-based B-cell epitopes and peptide immunotherapeutics targeting multiple solid tumor types: Emerging concepts and validation of combination immunotherapy

    PubMed Central

    Kaumaya, Pravin TP

    2015-01-01

    There is a recognizable and urgent need to speed the development and application of novel, more efficacious anti-cancer vaccine therapies that inhibit tumor progression and prevent acquisition of tumor resistance. We have created and established a portfolio of validated peptide epitopes against multiple receptor tyrosine kinases and we have identified the most biologically effective combinations of EGFR (HER-1), HER-2, HER-3, VEGF and IGF-1R peptide vaccines/mimics to selectively inhibit multiple receptors and signaling pathways. The strategy is based on the use of chimeric conformational B-cell epitope peptides incorporating “promiscuous” T-cell epitopes that afford the possibility of generating an enduring immune response, eliciting protein-reactive high-affinity anti-peptide antibodies as potential vaccines and peptide mimics that act as antagonists to receptor signaling that drive cancer metastasis. In this review we will summarize our ongoing studies based on the development of combinatorial immunotherapeutic strategies that act synergistically to enhance immune-mediated tumor killing aimed at addressing mechanisms of tumor resistance for several tumor types. PMID:25874884

  3. Designed Coiled-Coil Peptides Inhibit the Type Three Secretion System of Enteropathogenic Escherichia coli

    PubMed Central

    Larzábal, Mariano; Mercado, Elsa C.; Vilte, Daniel A.; Salazar-González, Hector; Cataldi, Angel; Navarro-Garcia, Fernando

    2010-01-01

    Background Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli (EHEC) are two categories of E. coli strains associated with human disease. A major virulence factor of both pathotypes is the expression of a type three secretion system (TTSS), responsible for their ability to adhere to gut mucosa causing a characteristic attaching and effacing lesion (A/E). The TTSS translocates effector proteins directly into the host cell that subvert mammalian cell biochemistry. Methods/Principal Findings We examined synthetic peptides designed to inhibit the TTSS. CoilA and CoilB peptides, both representing coiled-coil regions of the translocator protein EspA, and CoilD peptide, corresponding to a coiled–coil region of the needle protein EscF, were effective in inhibiting the TTSS dependent hemolysis of red blood cells by the EPEC E2348/69 strain. CoilA and CoilB peptides also reduced the formation of actin pedestals by the same strain in HEp-2 cells and impaired the TTSS-mediated protein translocation into the epithelial cell. Interestingly, CoilA and CoilB were able to block EspA assembly, destabilizing the TTSS and thereby Tir translocation. This blockage of EspA polymerization by CoilA or CoilB peptides, also inhibited the correct delivery of EspB and EspD as detected by immunoblotting. Interestingly, electron microscopy of bacteria incubated with the CoilA peptide showed a reduction of the length of EspA filaments. Conclusions Our data indicate that coiled-coil peptides can prevent the assembly and thus the functionality of the TTSS apparatus and suggest that these peptides could provide an attractive tool to block EPEC and EHEC pathogenesis. PMID:20140230

  4. Destabilization of Human Insulin Fibrils by Peptides of Fruit Bromelain Derived From Ananas comosus (Pineapple).

    PubMed

    Das, Sromona; Bhattacharyya, Debasish

    2017-12-01

    Deposition of insulin aggregates in human body leads to dysfunctioning of several organs. Effectiveness of fruit bromelain from pineapple in prevention of insulin aggregate was investigated. Proteolyses of bromelain was done as par human digestive system and the pool of small peptides was separated from larger peptides and proteins. Under conditions of growth of insulin aggregates from its monomers, this pool of peptides restricted the reaction upto formation of oligomers of limited size. These peptides also destabilized preformed insulin aggregates to oligomers. These processes were followed fluorimetrically using Thioflavin T and 1-ANS, size-exclusion HPLC, dynamic light scattering, atomic force microscopy, and transmission electron microscopy. Sequences of insulin (A and B chains) and bromelain were aligned using Clustal W software to predict most probable sites of interactions. Synthetic tripeptides corresponding to the hydrophobic interactive sites of bromelain showed disaggregation of insulin suggesting specificity of interactions. The peptides GG and AAA serving as negative controls showed no potency in destabilization of aggregates. Disaggregation potency of the peptides was also observed when insulin was deposited on HepG2 liver cells where no formation of toxic oligomers occurred. Amyloidogenic des-octapeptide (B23-B30 of insulin) incapable of cell signaling showed cytotoxicity similar to insulin. This toxicity could be neutralized by bromelain derived peptides. FT-IR and far-UV circular dichroism analysis indicated that disaggregated insulin had structure distinctly different from that of its hexameric (native) or monomeric states. Based on the stoichiometry of interaction and irreversibility of disaggregation, the mechanism/s of the peptides and insulin interactions has been proposed. J. Cell. Biochem. 118: 4881-4896, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Diagnostic Peptide Discovery: Prioritization of Pathogen Diagnostic Markers Using Multiple Features

    PubMed Central

    Carmona, Santiago J.; Sartor, Paula A.; Leguizamón, María S.; Campetella, Oscar E.; Agüero, Fernán

    2012-01-01

    The availability of complete pathogen genomes has renewed interest in the development of diagnostics for infectious diseases. Synthetic peptide microarrays provide a rapid, high-throughput platform for immunological testing of potential B-cell epitopes. However, their current capacity prevent the experimental screening of complete “peptidomes”. Therefore, computational approaches for prediction and/or prioritization of diagnostically relevant peptides are required. In this work we describe a computational method to assess a defined set of molecular properties for each potential diagnostic target in a reference genome. Properties such as sub-cellular localization or expression level were evaluated for the whole protein. At a higher resolution (short peptides), we assessed a set of local properties, such as repetitive motifs, disorder (structured vs natively unstructured regions), trans-membrane spans, genetic polymorphisms (conserved vs. divergent regions), predicted B-cell epitopes, and sequence similarity against human proteins and other potential cross-reacting species (e.g. other pathogens endemic in overlapping geographical locations). A scoring function based on these different features was developed, and used to rank all peptides from a large eukaryotic pathogen proteome. We applied this method to the identification of candidate diagnostic peptides in the protozoan Trypanosoma cruzi, the causative agent of Chagas disease. We measured the performance of the method by analyzing the enrichment of validated antigens in the high-scoring top of the ranking. Based on this measure, our integrative method outperformed alternative prioritizations based on individual properties (such as B-cell epitope predictors alone). Using this method we ranked 10 million 12-mer overlapping peptides derived from the complete T. cruzi proteome. Experimental screening of 190 high-scoring peptides allowed the identification of 37 novel epitopes with diagnostic potential, while none

  6. Preventative Maintenance.

    ERIC Educational Resources Information Center

    Migliorino, James

    Boards of education must be convinced that spending money up front for preventive maintenance will, in the long run, save districts' tax dollars. A good program of preventive maintenance can minimize disruption of service; reduce repair costs, energy consumption, and overtime; improve labor productivity and system equipment reliability; handle…

  7. Preventing ARDS

    PubMed Central

    Beitler, Jeremy R.; Schoenfeld, David A.

    2014-01-01

    Advances in critical care practice have led to a substantial decline in the incidence of ARDS over the past several years. Low tidal volume ventilation, timely resuscitation and antimicrobial administration, restrictive transfusion practices, and primary prevention of aspiration and nosocomial pneumonia have likely contributed to this reduction. Despite decades of research, there is no proven pharmacologic treatment of ARDS, and mortality from ARDS remains high. Consequently, recent initiatives have broadened the scope of lung injury research to include targeted prevention of ARDS. Prediction scores have been developed to identify patients at risk for ARDS, and clinical trials testing aspirin and inhaled budesonide/formoterol for ARDS prevention are ongoing. Future trials aimed at preventing ARDS face several key challenges. ARDS has not been validated as an end point for pivotal clinical trials, and caution is needed when testing toxic therapies that may prevent ARDS yet potentially increase mortality. PMID:25288000

  8. Peptide hormones and lung cancer.

    PubMed

    Moody, T W

    2006-03-01

    Several peptide hormones have been identified which alter the proliferation of lung cancer. Small cell lung cancer (SCLC), which is a neuroendocrine cancer, produces and secretes gastrin releasing peptide (GRP), neurotensin (NT) and adrenomedullin (AM) as autocrine growth factors. GRP, NT and AM bind to G-protein coupled receptors causing phosphatidylinositol turnover or elevated cAMP in SCLC cells. Addition of GRP, NT or AM to SCLC cells causes altered expression of nuclear oncogenes, such as c-fos, and stimulation of growth. Antagonists have been developed for GRP, NT and AM receptors which function as cytostatic agents and inhibit SCLC growth. Growth factor antagonists, such as the NT1 receptor antagonist SR48692, facilitate the ability of chemotherapeutic drugs to kill lung cancer cells. It remains to be determined if GRP, NT and AM receptors will served as molecular targets, for development of new therapies for the treatment of SCLC patients. Non-small cell lung cancer (NSCLC) cells also have a high density of GRP, NT, AM and epidermal growth factor (EGF) receptors. Several NSCLC patients with EGF receptor mutations respond to gefitinib, a tyrosine kinase inhibitor. Gefitinib relieves NSCLC symptoms, maintaining stable disease in patients who are not eligible for systemic chemotherapy. It is important to develop new therapeutic approaches using translational research techniques for the treatment of lung cancer patients.

  9. Robust peptide bundles designed computationally

    NASA Astrophysics Data System (ADS)

    Haider, Michael; Zhang, Huixi Violet; Kiick, Kristi; Saven, Jeffery; Pochan, Darrin

    Peptides are ideal candidates for the design and controlled assembly of nanoscale materials due to their potential to assemble with atomistic precision as in biological systems. Unlike other work utilizing natural proteins and structural motifs, this effort is completely de novo in order to build arbitrary structures with desired size for the specific placement and separation of functional groups. We have successfully computationally designed soluble, coiled coil, peptide, tetramer bundles which are robust and stable. Using circular dichroism we demonstrated the thermal stability of these bundles as well as confirmed their alpha helical and coiled coil nature. The stability of these bundles arises from the computational design of the coiled coil interior core residues. The coiled coil tetramer was confirmed to be the dominant species by analytical ultra-centrifugation sedimentation studies. We also established how these bundles behave in solution using small angle neutron scattering. The form factor of the bundles is well represented by a cylinder model and their behavior at high concentrations is modeled using a structure factor for aggregates of the cylinders. All of these experiments support our claim that the designed coiled coil bundles were achieved in solution. NSF DMREF 1234161.

  10. Amino-Terminal Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide

    PubMed Central

    McKie, Paul M.; Rodeheffer, Richard J.; Cataliotti, Alessandro; Martin, Fernando L.; Urban, Lynn H.; Mahoney, Douglas W.; Jacobsen, Steven J.; Redfield, Margaret M.; Burnett, John C.

    2007-01-01

    Recent studies report that, in the absence of heart failure and renal failure, plasma B-type natriuretic peptide (BNP) has prognostic value for mortality. We sought to confirm and extend these previous studies to assess BNP, measured by 3 distinct assays, as a biomarker for mortality in a strategy to enhance efforts at primary prevention and to better understand the clinical phenotype of such subjects at risk. We used a community-based cohort of 2042 subjects from Olmsted County, Minn, and individuals with heart or renal failure were excluded. BNP was assessed using 3 assays including Biosite and Shionogi for mature, biologically active BNP and the Roche assay for apparently nonbiologically active amino-terminal pro-BNP (NT-proBNP). Thorough echocardiographic and clinical data were recorded for all of the participants. Median follow-up for mortality was 5.6 years. BNP by all 3 of the assays was predictive of mortality. NT-proBNP and Biosite assays remained significant even after adjustment for traditional clinical risk factors and echocardiographic abnormalities including left ventricular hypertrophy and diastolic dysfunction. Echocardiography documented widespread structural changes in those with increasing BNP levels yet below levels observed in heart failure. We report in a large, well-characterized community-based cohort, free of heart failure, the first study to compare 3 distinct BNP assays as biomarkers for mortality in the same cohort. Our findings confirm the potential use of NT-proBNP and BNP biomarkers for future events and underscore that these peptides may also serve as biomarkers for underlying cardiac remodeling secondary to diverse cardiovascular disease entities. PMID:16585413

  11. [Effect of pineal gland peptides on morphofunctional structure of the pancreas in ageing].

    PubMed

    Ryzhak, A P; Kostiuchek, I N; Kvetnoĭ, I M

    2007-01-01

    A study of pineal gland peptides effect on morphology and functions of the pancreas in the model of premature ageing in rats was performed with respect to the need in methods for premature ageing prevention. Structural, morphological and functional alterations in pancreas tissue, suggesting premature ageing of the gland, were identified by methods of immunohistochemistry and electronic microscopy. There was registered a geroprotective effect of the pineal gland peptides on pancreas tissue, manifested in the resistance of the latter to the impact of stress factors entailing premature ageing.

  12. B-Type allatostatins and sex peptides

    USDA-ARS?s Scientific Manuscript database

    In many species, mating induces a number of behavioral changes in the female. For Drosophila melanogaster, the sex peptide (SP) has been identified as the main molecular factor behind these responses. Recently, the sex peptide receptor (SPR), a GPCR activated by SP has also been characterized as res...

  13. Peptide Mass Fingerprinting of Egg White Proteins

    ERIC Educational Resources Information Center

    Alty, Lisa T.; LaRiviere, Frederick J.

    2016-01-01

    Use of advanced mass spectrometry techniques in the undergraduate setting has burgeoned in the past decade. However, relatively few undergraduate experiments examine the proteomics tools of protein digestion, peptide accurate mass determination, and database searching, also known as peptide mass fingerprinting. In this experiment, biochemistry…

  14. [Application on food preservative of antimicrobial peptides].

    PubMed

    Zhao, Hongyan; Mu, Yu; Zhao, Baohua

    2009-07-01

    Antimicrobial peptides are an integral component of the innate immune system, it can counteract outer membrane pathogen such as bacteria, fungi, viruses, protozoan and so on. Owing to the sterilization and innocuity, it has the potential to be crude food preservative. In this paper the uses of antibacterial peptides in the food preservative were analyzed.

  15. Double quick, double click reversible peptide "stapling".

    PubMed

    Grison, Claire M; Burslem, George M; Miles, Jennifer A; Pilsl, Ludwig K A; Yeo, David J; Imani, Zeynab; Warriner, Stuart L; Webb, Michael E; Wilson, Andrew J

    2017-07-01

    The development of constrained peptides for inhibition of protein-protein interactions is an emerging strategy in chemical biology and drug discovery. This manuscript introduces a versatile, rapid and reversible approach to constrain peptides in a bioactive helical conformation using BID and RNase S peptides as models. Dibromomaleimide is used to constrain BID and RNase S peptide sequence variants bearing cysteine (Cys) or homocysteine ( h Cys) amino acids spaced at i and i + 4 positions by double substitution. The constraint can be readily removed by displacement of the maleimide using excess thiol. This new constraining methodology results in enhanced α-helical conformation (BID and RNase S peptide) as demonstrated by circular dichroism and molecular dynamics simulations, resistance to proteolysis (BID) as demonstrated by trypsin proteolysis experiments and retained or enhanced potency of inhibition for Bcl-2 family protein-protein interactions (BID), or greater capability to restore the hydrolytic activity of the RNAse S protein (RNase S peptide). Finally, use of a dibromomaleimide functionalized with an alkyne permits further divergent functionalization through alkyne-azide cycloaddition chemistry on the constrained peptide with fluorescein, oligoethylene glycol or biotin groups to facilitate biophysical and cellular analyses. Hence this methodology may extend the scope and accessibility of peptide stapling.

  16. Peptides and the blood-brain barrier.

    PubMed

    Banks, William A

    2015-10-01

    The demonstration that peptides and regulatory proteins can cross the blood-brain barrier (BBB) is one of the major contributions of Dr. Abba J. Kastin. He was the first to propose that peptides could cross the BBB, the first to show that an endogenous peptide did so, and the first to describe a saturable transport system at the BBB for peptides. His work shows that in crossing the BBB, peptides and regulatory proteins act as informational molecules, informing the brain of peripheral events. Brain-to-blood passage helps to control levels of peptides with the brain and can deliver information in the brain-to-blood direction. He showed that the transporters for peptides and proteins are not static, but respond to developmental and physiological changes and are affected by disease states. As such, the BBB is adaptive to the needs of the CNS, but when that adaption goes awry, the BBB can be a cause of disease. The mechanisms by which peptides and proteins cross the BBB offer opportunities for drug delivery of these substances or their analogs to the brain in the treatment of diseases of the central nervous system. Published by Elsevier Inc.

  17. Peptides and the blood–brain barrier

    PubMed Central

    Banks, William A.

    2016-01-01

    The demonstration that peptides and regulatory proteins can cross the blood–brain barrier (BBB) is one of the major contributions of Dr. Abba J. Kastin. He was the first to propose that peptides could cross the BBB, the first to show that an endogenous peptide did so, and the first to describe a saturable transport system at the BBB for peptides. His work shows that in crossing the BBB, peptides and regulatory proteins act as informational molecules, informing the brain of peripheral events. Brain-to-blood passage helps to control levels of peptides with the brain and can deliver information in the brain-to-blood direction. He showed that the transporters for peptides and proteins are not static, but respond to developmental and physiological changes and are affected by disease states. As such, the BBB is adaptive to the needs of the CNS, but when that adaption goes awry, the BBB can be a cause of disease. The mechanisms by which peptides and proteins cross the BBB offer opportunities for drug delivery of these substances or their analogs to the brain in the treatment of diseases of the central nervous system. PMID:25805003

  18. Exploring high-affinity binding properties of octamer peptides by principal component analysis of tetramer peptides.

    PubMed

    Kume, Akiko; Kawai, Shun; Kato, Ryuji; Iwata, Shinmei; Shimizu, Kazunori; Honda, Hiroyuki

    2017-02-01

    To investigate the binding properties of a peptide sequence, we conducted principal component analysis (PCA) of the physicochemical features of a tetramer peptide library comprised of 512 peptides, and the variables were reduced to two principal components. We selected IL-2 and IgG as model proteins and the binding affinity to these proteins was assayed using the 512 peptides mentioned above. PCA of binding affinity data showed that 16 and 18 variables were suitable for localizing IL-2 and IgG high-affinity binding peptides, respectively, into a restricted region of the PCA plot. We then investigated whether the binding affinity of octamer peptide libraries could be predicted using the identified region in the tetramer PCA. The results show that octamer high-affinity binding peptides were also concentrated in the tetramer high-affinity binding region of both IL-2 and IgG. The average fluorescence intensity of high-affinity binding peptides was 3.3- and 2.1-fold higher than that of low-affinity binding peptides for IL-2 and IgG, respectively. We conclude that PCA may be used to identify octamer peptides with high- or low-affinity binding properties from data from a tetramer peptide library. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  19. Superior Antifouling Performance of a Zwitterionic Peptide Compared to an Amphiphilic, Non-Ionic Peptide.

    PubMed

    Ye, Huijun; Wang, Libing; Huang, Renliang; Su, Rongxin; Liu, Boshi; Qi, Wei; He, Zhimin

    2015-10-14

    The aim of this study was to explore the influence of amphiphilic and zwitterionic structures on the resistance of protein adsorption to peptide self-assembled monolayers (SAMs) and gain insight into the associated antifouling mechanism. Two kinds of cysteine-terminated heptapeptides were studied. One peptide had alternating hydrophobic and hydrophilic residues with an amphiphilic sequence of CYSYSYS. The other peptide (CRERERE) was zwitterionic. Both peptides were covalently attached onto gold substrates via gold-thiol bond formation. Surface plasmon resonance analysis results showed that both peptide SAMs had ultralow or low protein adsorption amounts of 1.97-11.78 ng/cm2 in the presence of single proteins. The zwitterionic peptide showed relatively higher antifouling ability with single proteins and natural complex protein media. We performed molecular dynamics simulations to understand their respective antifouling behaviors. The results indicated that strong surface hydration of peptide SAMs contributes to fouling resistance by impeding interactions with proteins. Compared to the CYSYSYS peptide, more water molecules were predicted to form hydrogen-bonding interactions with the zwitterionic CRERERE peptide, which is in agreement with the antifouling test results. These findings reveal a clear relation between peptide structures and resistance to protein adsorption, facilitating the development of novel peptide-containing antifouling materials.

  20. Measuring peptide translocation into large unilamellar vesicles.

    PubMed

    Spinella, Sara A; Nelson, Rachel B; Elmore, Donald E

    2012-01-27

    There is an active interest in peptides that readily cross cell membranes without the assistance of cell membrane receptors(1). Many of these are referred to as cell-penetrating peptides, which are frequently noted for their potential as drug delivery vectors(1-3). Moreover, there is increasing interest in antimicrobial peptides that operate via non-membrane lytic mechanisms(4,5), particularly those that cross bacterial membranes without causing cell lysis and kill cells by interfering with intracellular processes(6,7). In fact, authors have increasingly pointed out the relationship between cell-penetrating and antimicrobial peptides(1,8). A firm understanding of the process of membrane translocation and the relationship between peptide structure and its ability to translocate requires effective, reproducible assays for translocation. Several groups have proposed methods to measure translocation into large unilamellar lipid vesicles (LUVs)(9-13). LUVs serve as useful models for bacterial and eukaryotic cell membranes and are frequently used in peptide fluorescent studies(14,15). Here, we describe our application of the method first developed by Matsuzaki and co-workers to consider antimicrobial peptides, such as magainin and buforin II(16,17). In addition to providing our protocol for this method, we also present a straightforward approach to data analysis that quantifies translocation ability using this assay. The advantages of this translocation assay compared to others are that it has the potential to provide information about the rate of membrane translocation and does not require the addition of a fluorescent label, which can alter peptide properties(18), to tryptophan-containing peptides. Briefly, translocation ability into lipid vesicles is measured as a function of the Foster Resonance Energy Transfer (FRET) between native tryptophan residues and dansyl phosphatidylethanolamine when proteins are associated with the external LUV membrane (Figure 1). Cell

  1. Circulating elastin peptides, role in vascular pathology.

    PubMed

    Robert, L; Labat-Robert, J

    2014-12-01

    The atherosclerotic process starts with the degradation of elastic fibers. Their presence was demonstrated in the circulation as well as several of their biological properties elucidated. We described years ago a procedure to obtain large elastin peptides by organo-alkaline hydrolysis, κ-elastin. This method enabled also the preparation of specific antibodies used to determine elastin peptides, as well as anti-elastin antibodies in body fluids and tissue extracts. Elastin peptides were determined in a large number of human blood samples. Studies were carried out to explore their pharmacological properties. Similar recent studies by other laboratories confirmed our findings and arose new interest in circulating elastin peptides for their biological activities. This recent trend justified the publication of a review of the biological and pathological activities of elastin peptides demonstrated during our previous studies, subject of this article. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  2. Harnessing supramolecular peptide nanotechnology in biomedical applications.

    PubMed

    Chan, Kiat Hwa; Lee, Wei Hao; Zhuo, Shuangmu; Ni, Ming

    2017-01-01

    The harnessing of peptides in biomedical applications is a recent hot topic. This arises mainly from the general biocompatibility of peptides, as well as from the ease of tunability of peptide structure to engineer desired properties. The ease of progression from laboratory testing to clinical trials is evident from the plethora of examples available. In this review, we compare and contrast how three distinct self-assembled peptide nanostructures possess different functions. We have 1) nanofibrils in biomaterials that can interact with cells, 2) nanoparticles that can traverse the bloodstream to deliver its payload and also be bioimaged, and 3) nanotubes that can serve as cross-membrane conduits and as a template for nanowire formation. Through this review, we aim to illustrate how various peptides, in their various self-assembled nanostructures, possess great promise in a wide range of biomedical applications and what more can be expected.

  3. Development of novel ligands for peptide GPCRs.

    PubMed

    Moran, Brian M; McKillop, Aine M; O'Harte, Finbarr Pm

    2016-12-01

    Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Chemical reactions directed Peptide self-assembly.

    PubMed

    Rasale, Dnyaneshwar B; Das, Apurba K

    2015-05-13

    Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly.

  5. Tumor-targeting peptides from combinatorial libraries*

    PubMed Central

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S.

    2018-01-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges infighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. PMID:27210583

  6. Chemical Reactions Directed Peptide Self-Assembly

    PubMed Central

    Rasale, Dnyaneshwar B.; Das, Apurba K.

    2015-01-01

    Fabrication of self-assembled nanostructures is one of the important aspects in nanoscience and nanotechnology. The study of self-assembled soft materials remains an area of interest due to their potential applications in biomedicine. The versatile properties of soft materials can be tuned using a bottom up approach of small molecules. Peptide based self-assembly has significant impact in biology because of its unique features such as biocompatibility, straight peptide chain and the presence of different side chain functionality. These unique features explore peptides in various self-assembly process. In this review, we briefly introduce chemical reaction-mediated peptide self-assembly. Herein, we have emphasised enzymes, native chemical ligation and photochemical reactions in the exploration of peptide self-assembly. PMID:25984603

  7. Probing Charge Transport through Peptide Bonds.

    PubMed

    Brisendine, Joseph M; Refaely-Abramson, Sivan; Liu, Zhen-Fei; Cui, Jing; Ng, Fay; Neaton, Jeffrey B; Koder, Ronald L; Venkataraman, Latha

    2018-02-15

    We measure the conductance of unmodified peptides at the single-molecule level using the scanning tunneling microscope-based break-junction method, utilizing the N-terminal amine group and the C-terminal carboxyl group as gold metal-binding linkers. Our conductance measurements of oligoglycine and oligoalanine backbones do not rely on peptide side-chain linkers. We compare our results with alkanes terminated asymmetrically with an amine group on one end and a carboxyl group on the other to show that peptide bonds decrease the conductance of an otherwise saturated carbon chain. Using a newly developed first-principles approach, we attribute the decrease in conductance to charge localization at the peptide bond, which reduces the energy of the frontier orbitals relative to the Fermi energy and the electronic coupling to the leads, lowering the tunneling probability. Crucially, this manifests as an increase in conductance decay of peptide backbones with increasing length when compared with alkanes.

  8. Tumor-targeting peptides from combinatorial libraries.

    PubMed

    Liu, Ruiwu; Li, Xiaocen; Xiao, Wenwu; Lam, Kit S

    2017-02-01

    Cancer is one of the major and leading causes of death worldwide. Two of the greatest challenges in fighting cancer are early detection and effective treatments with no or minimum side effects. Widespread use of targeted therapies and molecular imaging in clinics requires high affinity, tumor-specific agents as effective targeting vehicles to deliver therapeutics and imaging probes to the primary or metastatic tumor sites. Combinatorial libraries such as phage-display and one-bead one-compound (OBOC) peptide libraries are powerful approaches in discovering tumor-targeting peptides. This review gives an overview of different combinatorial library technologies that have been used for the discovery of tumor-targeting peptides. Examples of tumor-targeting peptides identified from each combinatorial library method will be discussed. Published tumor-targeting peptide ligands and their applications will also be summarized by the combinatorial library methods and their corresponding binding receptors. Copyright © 2017. Published by Elsevier B.V.

  9. Peptide-Lipid Interactions: Experiments and Applications

    PubMed Central

    Galdiero, Stefania; Falanga, Annarita; Cantisani, Marco; Vitiello, Mariateresa; Morelli, Giancarlo; Galdiero, Massimiliano

    2013-01-01

    The interactions between peptides and lipids are of fundamental importance in the functioning of numerous membrane-mediated cellular processes including antimicrobial peptide action, hormone-receptor interactions, drug bioavailability across the blood-brain barrier and viral fusion processes. Moreover, a major goal of modern biotechnology is obtaining new potent pharmaceutical agents whose biological action is dependent on the binding of peptides to lipid-bilayers. Several issues need to be addressed such as secondary structure, orientation, oligomerization and localization inside the membrane. At the same time, the structural effects which the peptides cause on the lipid bilayer are important for the interactions and need to be elucidated. The structural characterization of membrane active peptides in membranes is a harsh experimental challenge. It is in fact accepted that no single experimental technique can give a complete structural picture of the interaction, but rather a combination of different techniques is necessary. PMID:24036440

  10. Novel peptides from adrenomedullary chromaffin vesicles.

    PubMed Central

    Sigafoos, J; Chestnut, W G; Merrill, B M; Taylor, L C; Diliberto, E J; Viveros, O H

    1993-01-01

    The adrenal medulla chromaffin vesicle (CV) contains, on a weight basis, as much soluble protein and peptide as catecholamine. The bulk of the protein is accounted for by chromogranins (Cgr) A, B and C. Additionally, a large variety of neuropeptides and their precursor proteins have been found recently within these vesicles. Nevertheless, fractionation of CV lysates indicates the presence of many more peptides than previously reported. In the hope of finding novel bioactive peptides, we initiated a systematic isolation and characterisation of CV peptides. Bovine CV pellets were prepared by sucrose gradient centrifugation and immediately boiled in water to avoid degradation of native proteins and peptides. The water lysates were fractionated through a battery of reversed-phase and ion-exchange high-performance chromatographic steps. We fully or partially characterised a substantial number of novel peptides derived from CgrA and CgrB. A tetradecapeptide and a 13 kDa extended peptide were derived from the bovine homologue of rat secretogranin III. Peptides corresponding to C-terminal fragments of 7B2 and proteoglycan II were also found. Additionally, several sequences had no known precursors. Of the sequences derived from known precursors some corresponded to fragments bracketed by pairs of basic amino acids, but others were preceded or followed by single basic residues or by unusual putative cleavage sites. Some of these peptides were postranslationally modified (pyroglutamylation, glycosylation, phosphorylation, amidation). A significant degree of structural conservation of some of these peptides across species suggests that they may exert biological effects when cosecreted with catecholamines during splanchnic stimulation. PMID:8300415

  11. Spectroscopic investigation of Ginkgo biloba terpene trilactones and their interaction with amyloid peptide Aβ(25-35)

    NASA Astrophysics Data System (ADS)

    He, Jiangtao; Petrovic, Ana G.; Dzyuba, Sergei V.; Berova, Nina; Nakanishi, Koji; Polavarapu, Prasad L.

    2008-04-01

    The beneficial effects of Ginkgo biloba extract in the "treatment" of dementia are attributed to its terpene trilactone (TTL) constituents. The interactions between TTLs and amyloid peptide are believed to be responsible in preventing the aggregation of peptide. These interactions have been investigated using infrared vibrational absorption (VA) and circular dichroism (VCD) spectra. Four TTLs, namely ginkgolide A (GA), ginkgolide B (GB), ginkgolide C (GC) and bilobalide (BB) and amyloid Aβ(25-35) peptide, as a model for the full length peptide, are used in this study. GA-monoether and GA-diether have also been synthesized and investigated to help understand the role of individual carbonyl groups in these interactions. The precipitation and solubility issues encountered with the mixture of ginkgolide + Aβ peptide for VA and VCD studies were overcome using binary ethanol-D 2O solvent mixture. The experimental VA and VCD spectra of GA, GB, GC and BB, GA-monoether and GA-diether have been analyzed using the corresponding spectra predicted with density functional theory. The time-dependent experimental VA and VCD spectra of Aβ(25-35) peptide and the corresponding experimental spectra in the presence of TTLs indicated that the effect of the TTLs in modulating the aggregation of Aβ(25-35) peptide is relatively small. Such small effects might indicate the absence of a specific interaction between the TTLs and Aβ(25-35) peptide as a major force leading to the reduced aggregation of amyloid peptides. It is possible that the therapeutic effect of G. biloba extract does not originate from direct interactions between TTLs and the Aβ(25-35) peptide and is more complex.

  12. A synthetic peptide shows retro- and anterograde neuronal transport before disrupting the chemosensation of plant-pathogenic nematodes.

    PubMed

    Wang, Dong; Jones, Laura M; Urwin, Peter E; Atkinson, Howard J

    2011-03-07

    Cyst nematodes are a group of plant pathogens each with a defined host range that cause major losses to crops including potato, soybean and sugar beet. The infective mobile stage hatches from dormant eggs and moves a short distance through the soil to plant roots, which it then invades. A novel strategy for control has recently been proposed in which the plant is able to secrete a peptide which disorientates the infective stage and prevents invasion of the pathogen. This study provides indirect evidence to support the mechanism by which one such peptide disrupts chemosensory function in nematodes. The peptide is a disulphide-constrained 7-mer with the amino acid sequence CTTMHPRLC that binds to nicotinic acetylcholine receptors. A fluorescently tagged version of this peptide with both epifluorescent and confocal microscopy was used to demonstrate that retrograde transport occurs from an aqueous environment along bare-ending primary cilia of chemoreceptive sensilla. The peptide is transported to the cell bodies of these neurons and on to a limited number of other neurons to which they connect. It appears to be localised in both neuronal processes and organelles adjacent to nuclei of some neurons suggesting it could be transported through the Golgi apparatus. The peptide takes 2.5 h to reach the neuronal cell bodies. Comparative studies established that similar but less abundant uptake occurs for Caenorhabditis elegans along its well studied dye-filling chemoreceptive neurons. Incubation in peptide solution or root-exudate from transgenic plants that secrete the peptide disrupted normal orientation of infective cyst nematodes to host root diffusate. The peptide probably undergoes transport along the dye-filling non-cholinergic chemoreceptive neurons to their synapses where it is taken up by the interneurons to which they connect. Coordinated responses to chemoreception are disrupted when the sub-set of cholinergic interneurons secrete the peptide at synapses that

  13. Prenatal treatment prevents learning deficit in Down syndrome model.

    PubMed

    Incerti, Maddalena; Horowitz, Kari; Roberson, Robin; Abebe, Daniel; Toso, Laura; Caballero, Madeline; Spong, Catherine Y

    2012-01-01

    Down syndrome is the most common genetic cause of mental retardation. Active fragments of neurotrophic factors release by astrocyte under the stimulation of vasoactive intestinal peptide, NAPVSIPQ (NAP) and SALLRSIPA (SAL) respectively, have shown therapeutic potential for developmental delay and learning deficits. Previous work demonstrated that NAP+SAL prevent developmental delay and glial deficit in Ts65Dn that is a well-characterized mouse model for Down syndrome. The objective of this study is to evaluate if prenatal treatment with these peptides prevents the learning deficit in the Ts65Dn mice. Pregnant Ts65Dn female and control pregnant females were randomly treated (intraperitoneal injection) on pregnancy days 8 through 12 with saline (placebo) or peptides (NAP 20 µg +SAL 20 µg) daily. Learning was assessed in the offspring (8-10 months) using the Morris Watermaze, which measures the latency to find the hidden platform (decrease in latency denotes learning). The investigators were blinded to the prenatal treatment and genotype. Pups were genotyped as trisomic (Down syndrome) or euploid (control) after completion of all tests. two-way ANOVA followed by Neuman-Keuls test for multiple comparisons, P<0.05 was used to denote statistical significance. Trisomic mice who prenatally received placebo (Down syndrome-placebo; n = 11) did not demonstrate learning over the five day period. DS mice that were prenatally exposed to peptides (Down syndrome-peptides; n = 10) learned significantly better than Down syndrome-placebo (p<0.01), and similar to control-placebo (n = 33) and control-peptide (n = 30). In conclusion prenatal treatment with the neuroprotective peptides (NAP+SAL) prevented learning deficits in a Down syndrome model. These findings highlight a possibility for the prevention of sequelae in Down syndrome and suggest a potential pregnancy intervention that may improve outcome.

  14. Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.

    PubMed

    Spong, C Y; Abebe, D T; Gozes, I; Brenneman, D E; Hill, J M

    2001-05-01

    Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.

  15. Prevent Cyberbullying

    MedlinePlus

    ... Tips for Teachers Report Cyberbullying Print Share Prevent Cyberbullying Be Aware of What Your Kids are Doing ... Signs a Child is Being Cyberbullied or is Cyberbullying Others Many of the warning signs that cyberbullying ...

  16. Preventing accidents

    DOT National Transportation Integrated Search

    2005-08-01

    As the most effective strategy for improving safety is to prevent accidents from occurring at all, the Volpe Center applies a broad range of research techniques and capabilities to determine causes and consequences of accidents and to identify, asses...

  17. Preventing falls

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000052.htm Preventing falls To use the sharing features on this page, please enable JavaScript. People with medical problems are at risk of falling or tripping. This can result in ...

  18. Preventing stroke

    MedlinePlus

    ... chap 65. Goldstein LB. Prevention and management of ischemic stroke. In: Mann DL, Zipes DP, Libby P, Bonow ... Editorial team. Related MedlinePlus Health Topics Hemorrhagic Stroke Ischemic Stroke Stroke Browse the Encyclopedia A.D.A.M., ...

  19. Preventing Rejection

    MedlinePlus

    ... for you to prevent causing harmful medication interactions. Organization tips Get into a routine of taking your ... Organ Sharing , a non-profit 501(c)(3) organization | Guidestar | Sitemap | Legal Share This https://www.facebook. ...

  20. Antimicrobial peptides interact with peptidoglycan

    NASA Astrophysics Data System (ADS)

    Neelay, Om P.; Peterson, Christian A.; Snavely, Mary E.; Brown, Taylor C.; TecleMariam, Ariam F.; Campbell, Jennifer A.; Blake, Allison M.; Schneider, Sydney C.; Cremeens, Matthew E.

    2017-10-01

    Traditional therapeutics are losing effectiveness as bacterial resistance increases, and antimicrobial peptides (AMPs) can serve as an alternative source for antimicrobial agents. Their mode of action is commonly hypothesized to involve pore formation in the lipid membrane, thereby leading to cell death. However, bacterial cell walls are much more complex than just the lipid membrane. A large portion of the wall is comprised of peptidoglycan, yet we did not find any report of AMP-peptidoglycan interactions. Consequently, this work evaluated AMP-peptidoglycan and AMP-phospholipid (multilamellar vesicles) interactions through tryptophan fluorescence. Given that peptidoglycan is insoluble and vesicles are large particles, we took advantage of the unique properties of Trp-fluorescence to use one technique for two very different systems. Interestingly, melittin and cecropin A interacted with peptidoglycan to a degree similar to vancomycin, a positive control. Whether these AMP-peptidoglycan interactions relate to a killing mode of action requires further study.

  1. Virtual screening of a milk peptide database for the identification of food-derived antimicrobial peptides.

    PubMed

    Liu, Yufang; Eichler, Jutta; Pischetsrieder, Monika

    2015-11-01

    Milk provides a wide range of bioactive substances, such as antimicrobial peptides and proteins. Our study aimed to identify novel antimicrobial peptides naturally present in milk. The components of an endogenous bovine milk peptide database were virtually screened for charge, amphipathy, and predicted secondary structure. Thus, 23 of 248 screened peptides were identified as candidates for antimicrobial effects. After commercial synthesis, their antimicrobial activities were determined against Escherichia coli NEB5α, E. coli ATCC25922, and Bacillus subtilis ATCC6051. In the tested concentration range (<2 mM), bacteriostatic activity of 14 peptides was detected including nine peptides inhibiting both Gram-positive and Gram-negative bacteria. The most effective fragment was TKLTEEEKNRLNFLKKISQRYQKFΑLPQYLK corresponding to αS2 -casein151-181 , with minimum inhibitory concentration (MIC) of 4.0 μM against B. subtilis ATCC6051, and minimum inhibitory concentrations of 16.2 μM against both E. coli strains. Circular dichroism spectroscopy revealed conformational changes of most active peptides in a membrane-mimic environment, transitioning from an unordered to α-helical structure. Screening of food peptide databases by prediction tools is an efficient method to identify novel antimicrobial food-derived peptides. Milk-derived antimicrobial peptides may have potential use as functional food ingredients and help to understand the molecular mechanisms of anti-infective milk effects. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Analysis of the endogenous peptide profile of milk: identification of 248 mainly casein-derived peptides.

    PubMed

    Baum, Florian; Fedorova, Maria; Ebner, Jennifer; Hoffmann, Ralf; Pischetsrieder, Monika

    2013-12-06

    Milk is an excellent source of bioactive peptides. However, the composition of the native milk peptidome has only been partially elucidated. The present study applied matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) directly or after prefractionation of the milk peptides by reverse-phase high-performance liquid chromatography (RP-HPLC) or OFFGEL fractionation for the comprehensive analysis of the peptide profile of raw milk. The peptide sequences were determined by MALDI-TOF/TOF or nano-ultra-performance liquid chromatography-nanoelectrospray ionization-LTQ-Orbitrap-MS. Direct MALDI-TOF-MS analysis led to the assignment of 57 peptides. Prefractionation by both complementary methods led to the assignment of another 191 peptides. Most peptides originate from α(S1)-casein, followed by β-casein, and α(S2)-casein. κ-Casein and whey proteins seem to play only a minor role as peptide precursors. The formation of many, but not all, peptides could be explained by the activity of the endogenous peptidases, plasmin or cathepsin D, B, and G. Database searches revealed the presence of 22 peptides with established physiological function, including those with angiotensin-converting-enzyme (ACE) inhibitory, immunomodulating, or antimicrobial activity.

  3. Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.

    PubMed

    Kato, Ryuji; Kaga, Chiaki; Kunimatsu, Mitoshi; Kobayashi, Takeshi; Honda, Hiroyuki

    2006-06-01

    Peptide array, the designable peptide library covalently synthesized on cellulose support, was applied to assay peptide-cell interaction, between solid-bound peptides and anchorage-dependant cells, to study objective peptide design. As a model case, cell-adhesive peptides that could enhance cell growth as tissue engineering scaffold material, was studied. On the peptide array, the relative cell-adhesion ratio of NIH/3T3 cells was 2.5-fold higher on the RGDS (Arg-Gly-Asp-Ser) peptide spot as compared to the spot with no peptide, thus indicating integrin-mediated peptide-cell interaction. Such strong cell adhesion mediated by the RGDS peptide was easily disrupted by single residue substitution on the peptide array, thus indicating that the sequence recognition accuracy of cells was strictly conserved in our optimized scheme. The observed cellular morphological extension with active actin stress-fiber on the RGD motif-containing peptide supported our strategy that peptide array-based interaction assay of solid-bound peptide and anchorage-dependant cells (PIASPAC) could provide quantitative data on biological peptide-cell interaction. The analysis of 180 peptides obtained from fibronectin type III domain (no. 1447-1629) yielded 18 novel cell-adhesive peptides without the RGD motif. Taken together with the novel candidates, representative rules of ineffective amino acid usage were obtained from non-effective candidate sequences for the effective designing of cell-adhesive peptides. On comparing the amino acid usage of the top 20 and last 20 peptides from the 180 peptides, the following four brief design rules were indicated: (i) Arg or Lys of positively charged amino acids (except His) could enhance cell adhesion, (ii) small hydrophilic amino acids are favored in cell-adhesion peptides, (iii) negatively charged amino acids and small amino acids (except Gly) could reduce cell adhesion, and (iv) Cys and Met could be excluded from the sequence combination since they have

  4. ACTG: novel peptide mapping onto gene models.

    PubMed

    Choi, Seunghyuk; Kim, Hyunwoo; Paek, Eunok

    2017-04-15

    In many proteogenomic applications, mapping peptide sequences onto genome sequences can be very useful, because it allows us to understand origins of the gene products. Existing software tools either take the genomic position of a peptide start site as an input or assume that the peptide sequence exactly matches the coding sequence of a given gene model. In case of novel peptides resulting from genomic variations, especially structural variations such as alternative splicing, these existing tools cannot be directly applied unless users supply information about the variant, either its genomic position or its transcription model. Mapping potentially novel peptides to genome sequences, while allowing certain genomic variations, requires introducing novel gene models when aligning peptide sequences to gene structures. We have developed a new tool called ACTG (Amino aCids To Genome), which maps peptides to genome, assuming all possible single exon skipping, junction variation allowing three edit distances from the original splice sites, exon extension and frame shift. In addition, it can also consider SNVs (single nucleotide variations) during mapping phase if a user provides the VCF (variant call format) file as an input. Available at http://prix.hanyang.ac.kr/ACTG/search.jsp . eunokpaek@hanyang.ac.kr. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

  5. Designing Antibacterial Peptides with Enhanced Killing Kinetics

    PubMed Central

    Waghu, Faiza H.; Joseph, Shaini; Ghawali, Sanket; Martis, Elvis A.; Madan, Taruna; Venkatesh, Kareenhalli V.; Idicula-Thomas, Susan

    2018-01-01

    Antimicrobial peptides (AMPs) are gaining attention as substitutes for antibiotics in order to combat the risk posed by multi-drug resistant pathogens. Several research groups are engaged in design of potent anti-infective agents using natural AMPs as templates. In this study, a library of peptides with high sequence similarity to Myeloid Antimicrobial Peptide (MAP) family were screened using popular online prediction algorithms. These peptide variants were designed in a manner to retain the conserved residues within the MAP family. The prediction algorithms were found to effectively classify peptides based on their antimicrobial nature. In order to improve the activity of the identified peptides, molecular dynamics (MD) simulations, using bilayer and micellar systems could be used to design and predict effect of residue substitution on membranes of microbial and mammalian cells. The inference from MD simulation studies well corroborated with the wet-lab observations indicating that MD-guided rational design could lead to discovery of potent AMPs. The effect of the residue substitution on membrane activity was studied in greater detail using killing kinetic analysis. Killing kinetics studies on Gram-positive, negative and human erythrocytes indicated that a single residue change has a drastic effect on the potency of AMPs. An interesting outcome was a switch from monophasic to biphasic death rate constant of Staphylococcus aureus due to a single residue mutation in the peptide. PMID:29527201

  6. Unusual reactivity of a silver mineralizing peptide.

    PubMed

    Carter, Carly Jo; Ackerson, Christopher J; Feldheim, Daniel L

    2010-07-27

    The ability of peptides selected via phage display to mediate the formation of inorganic nanoparticles is now well established. The atomic-level interactions between the selected peptides and the metal ion precursors are in most instances, however, largely obscure. We identified a new peptide sequence that is capable of mediating the formation of Ag nanoparticles. Surprisingly, nanoparticle formation requires the presence of peptide, HEPES buffer, and light; the absence of any one of these compromises nanoparticle formation. Electrochemical experiments revealed that the peptide binds Ag+ in a 3 Ag+:1 peptide ratio and significantly alters the Ag+ reduction potential. Alanine replacement studies yielded insight into the sequence-function relationships of Ag nanoparticle formation, including the Ag+ coordination sites and the residues necessary for Ag synthesis. In addition, the peptide was found to function when immobilized onto surfaces, and the specific immobilizing concentration could be adjusted to yield either spherical Ag nanoparticles or high aspect ratio nanowires. These studies further illustrate the range of interesting new solid-state chemistries possible using biomolecules.

  7. Unusual Reactivity of a Silver Mineralizing Peptide

    PubMed Central

    Carter, Carly Jo; Ackerson, Christopher J.; Feldheim, Daniel L.

    2010-01-01

    The ability of peptides selected via phage display to mediate the formation of inorganic nanoparticles is now well established. The atomic-level interactions between the selected peptides and the metal ion precursors are in most instances, however, largely obscure. We identified a new peptide sequence that is capable of mediating the formation of Ag nanoparticles. Surprisingly, nanoparticle formation requires the presence of peptide, HEPES buffer, and light; the absence of any one of these compromises nanoparticle formation. Electrochemical experiments revealed that the peptide binds Ag+ in a 3 Ag+:1 peptide ratio and significantly alters the Ag+ reduction potential. Alanine replacement studies yielded insight into the sequence-function relationships of Ag nanoparticle formation, including the Ag+ coordination sites and the residues necessary for Ag synthesis. In addition, the peptide was found to function when immobilized onto surfaces, and the specific immobilizing concentration could be adjusted to yield either spherical Ag nanoparticles or high aspect ratio nanowires. These studies further illustrate the range of interesting new solid-state chemistries possible using biomolecules. PMID:20552994

  8. Multiplex De Novo Sequencing of Peptide Antibiotics

    NASA Astrophysics Data System (ADS)

    Mohimani, Hosein; Liu, Wei-Ting; Yang, Yu-Liang; Gaudêncio, Susana P.; Fenical, William; Dorrestein, Pieter C.; Pevzner, Pavel A.

    Proliferation of drug-resistant diseases raises the challenge of searching for new, more efficient antibiotics. Currently, some of the most effective antibiotics (i.e., Vancomycin and Daptomycin) are cyclic peptides produced by non-ribosomal biosynthetic pathways. The isolation and sequencing of cyclic peptide antibiotics, unlike the same activity with linear peptides, is time-consuming and error-prone. The dominant technique for sequencing cyclic peptides is NMR-based and requires large amounts (milligrams) of purified materials that, for most compounds, are not possible to obtain. Given these facts, there is a need for new tools to sequence cyclic NRPs using picograms of material. Since nearly all cyclic NRPs are produced along with related analogs, we develop a mass spectrometry approach for sequencing all related peptides at once (in contrast to the existing approach that analyzes individual peptides). Our results suggest that instead of attempting to isolate and NMR-sequence the most abundant compound, one should acquire spectra of many related compounds and sequence all of them simultaneously using tandem mass spectrometry. We illustrate applications of this approach by sequencing new variants of cyclic peptide antibiotics from Bacillus brevis, as well as sequencing a previously unknown familiy of cyclic NRPs produced by marine bacteria.

  9. Potent and Selective Peptide-based Inhibition of the G Protein Gαq*

    PubMed Central

    Charpentier, Thomas H.; Waldo, Gary L.; Lowery-Gionta, Emily G.; Krajewski, Krzysztof; Strahl, Brian D.; Kash, Thomas L.; Harden, T. Kendall; Sondek, John

    2016-01-01

    In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gαq binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gαq within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gαq in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gαq. A representative peptide was specific for active Gαq because it did not bind inactive Gαq or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ1γ2. In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gαq; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gαq in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gαq-dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gαq in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gαq in cells. PMID:27742837

  10. Potent and Selective Peptide-based Inhibition of the G Protein Gαq.

    PubMed

    Charpentier, Thomas H; Waldo, Gary L; Lowery-Gionta, Emily G; Krajewski, Krzysztof; Strahl, Brian D; Kash, Thomas L; Harden, T Kendall; Sondek, John

    2016-12-02

    In contrast to G protein-coupled receptors, for which chemical and peptidic inhibitors have been extensively explored, few compounds are available that directly modulate heterotrimeric G proteins. Active Gα q binds its two major classes of effectors, the phospholipase C (PLC)-β isozymes and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashion: a continuous helix-turn-helix of the effectors engages Gα q within its canonical binding site consisting of a groove formed between switch II and helix α3. This information was exploited to synthesize peptides that bound active Gα q in vitro with affinities similar to full-length effectors and directly competed with effectors for engagement of Gα q A representative peptide was specific for active Gα q because it did not bind inactive Gα q or other classes of active Gα subunits and did not inhibit the activation of PLC-β3 by Gβ 1 γ 2 In contrast, the peptide robustly prevented activation of PLC-β3 or p63RhoGEF by Gα q ; it also prevented G protein-coupled receptor-promoted neuronal depolarization downstream of Gα q in the mouse prefrontal cortex. Moreover, a genetically encoded form of this peptide flanked by fluorescent proteins inhibited Gα q -dependent activation of PLC-β3 at least as effectively as a dominant-negative form of full-length PLC-β3. These attributes suggest that related, cell-penetrating peptides should effectively inhibit active Gα q in cells and that these and genetically encoded sequences may find application as molecular probes, drug leads, and biosensors to monitor the spatiotemporal activation of Gα q in cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. Chimeric Peptides as Implant Functionalization Agents for Titanium Alloy Implants with Antimicrobial Properties

    NASA Astrophysics Data System (ADS)

    Yucesoy, Deniz T.; Hnilova, Marketa; Boone, Kyle; Arnold, Paul M.; Snead, Malcolm L.; Tamerler, Candan

    2015-04-01

    Implant-associated infections can have severe effects on the longevity of implant devices and they also represent a major cause of implant failures. Treating these infections associated with implants by antibiotics is not always an effective strategy due to poor penetration rates of antibiotics into biofilms. Additionally, emerging antibiotic resistance poses serious concerns. There is an urge to develop effective antibacterial surfaces that prevent bacterial adhesion and proliferation. A novel class of bacterial therapeutic agents, known as antimicrobial peptides (AMPs), are receiving increasing attention as an unconventional option to treat septic infection, partly due to their capacity to stimulate innate immune responses and for the difficulty of microorganisms to develop resistance towards them. While host and bacterial cells compete in determining the ultimate fate of the implant, functionalization of implant surfaces with AMPs can shift the balance and prevent implant infections. In the present study, we developed a novel chimeric peptide to functionalize the implant material surface. The chimeric peptide simultaneously presents two functionalities, with one domain binding to a titanium alloy implant surface through a titanium-binding domain while the other domain displays an antimicrobial property. This approach gains strength through control over the bio-material interfaces, a property built upon molecular recognition and self-assembly through a titanium alloy binding domain in the chimeric peptide. The efficiency of chimeric peptide both in-solution and absorbed onto titanium alloy surface was evaluated in vitro against three common human host infectious bacteria, Streptococcus mutans, Staphylococcus epidermidis, and Escherichia coli. In biological interactions such as occur on implants, it is the surface and the interface that dictate the ultimate outcome. Controlling the implant surface by creating an interface composed chimeric peptides may therefore

  12. Cancer prevention.

    PubMed

    Tubiana, M

    1999-01-01

    Over 70% of human cancers are associated with lifestyle and about half of cancer deaths could be prevented by relatively simple individual actions: no smoking, moderate consumption of alcohol, increased consumption of fruit and vegetables, avoidance of sunbathing, obesity and a too high consumption of saturated lipids. Most of these efforts would also markedly decrease the incidence of cardiovascular and respiratory diseases. However, the concept of prevention is currently neither well accepted nor understood by the medical community and the general public. It is often felt that it restricts freedom, imposes a choice between pleasure and duty, and that passing judgement on lifestyle is a form of intolerance. The case of tobacco illustrates the difficulties encountered by prevention, notably among adolescents. The fight against smoking requires information, a societal approach (ban on advertising, increase in price), and a reduction of the example given by adult smoking (parents, peers, teachers, physicians, TV presenters, movie stars, have a great influence on adolescents), while tobacco cessation programs must be promoted. The various approaches should be integrated into a global program of health prevention, including health education at school from 5 to 12 years of age. The efficacy of each of the global program's components should be evaluated. Misconceptions such as overestimation of the impact of pollution on health should also be corrected. Health is created and experienced by people within the setting of their daily lives, in particular during childhood. Prevention is the responsibility of individual members of the community but also of the community as a whole.

  13. [Delirium Prevention].

    PubMed

    Restrepo Bernal, Diana; Niño García, Jorge Andrés; Ortiz Estévez, Daniel Eduardo

    2016-01-01

    Delirium is the most prevalent neuropsychiatric syndrome in the general hospital. Its presence is a marker of poor prognosis for patients. Its prevention could be the most effective strategy for reducing its frequency and its complications. To review recent findings and strategies for the prevention of delirium. A non-systematic review of scientific articles published in the last ten years in Spanish and English. A search was made in databases such as MEDLINE, Cochrane, EMBASE, Ovid, and ScienceDirect, for articles that included the terms, delirium and prevention. Identification of predisposing and precipitating factors for delirium and a better understanding of the pathophysiological mechanisms underlying the onset of delirium have enabled the implementation of various pharmacological and non-pharmacological strategies in patients at high risk to develop hospital delirium. The studies to prevent delirium have focused on surgical patients. The current evidence supports the daily implementation of non-pharmacological measures to prevent delirium, as they are easy and cost effective. The available evidence is still limited to recommend the daily use of pharmacological strategies in delirium prophylaxis, and there is a consensus against the modest use of antipsychotic drugs in surgical patients and dexmedetomidine in patients in intensive care. New high-quality clinical trials and studies involving non-surgical patients are needed to provide more evidence about this subject. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  14. Quantitative analysis of pyroglutamic acid in peptides.

    PubMed

    Suzuki, Y; Motoi, H; Sato, K

    1999-08-01

    A simplified and rapid procedure for the determination of pyroglutamic acid in peptides was developed. The method involves the enzymatic cleavage of an N-terminal pyroglutamate residue using a thermostable pyroglutamate aminopeptidase and isocratic HPLC separation of the resulting enzymatic hydrolysate using a column switching technique. Pyroglutamate aminopeptidase from a thermophilic archaebacteria, Pyrococcus furiosus, cleaves N-terminal pyroglutamic acid residue independent of the molecular weight of the substrate. It cleaves more than 85% of pyroglutamate from peptides whose molecular weight ranges from 362.4 to 4599.4 Da. Thus, a new method is presented that quantitatively estimates N-terminal pyroglutamic acid residue in peptides.

  15. Cysteine-containing peptides having antioxidant properties

    DOEpatents

    Bielicki, John K [Castro Valley, CA

    2009-10-13

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  16. Cysteine-containing peptides having antioxidant properties

    DOEpatents

    Bielicki, John K [Castro Valley, CA

    2008-10-21

    Cysteine containing amphipathic alpha helices of the exchangeable apolipoproteins, as exemplified by apolipoprotein (apo) A-I.sub.Milano (R173C) and apoA-I.sub.Paris, (R151C) were found to exhibit potent antioxidant activity on phospholipid surfaces. The addition of a free thiol, at the hydrophobic/hydrophilic interface of an amphipathic alpha helix of synthetic peptides that mimic HDL-related proteins, imparts a unique antioxidant activity to these peptides which inhibits lipid peroxidation and protects phospholipids from water-soluble free radical initiators. These peptides can be used as therapeutic agents to combat cardiovascular disease, ischemia, bone disease and other inflammatory related diseases.

  17. How Nature Morphs Peptide Scaffolds into Antibiotics

    PubMed Central

    Nolan, Elizabeth M.; Walsh, Christopher T.

    2010-01-01

    The conventional notion that peptides are poor candidates for orally available drugs because of protease-sensitive peptide bonds, intrinsic hydrophilicity, and ionic charges contrasts with the diversity of antibiotic natural products with peptide-based frameworks that are synthesized and utilized by Nature. Several of these antibiotics, including penicillin and vancomycin, are employed to treat bacterial infections in humans and have been best-selling therapeutics for decades. Others might provide new platforms for the design of novel therapeutics to combat emerging antibiotic-resistant bacterial pathogens. PMID:19058272

  18. The Potential of Antimicrobial Peptides as Biocides

    PubMed Central

    Laverty, Garry; Gorman, Sean P.; Gilmore, Brendan F.

    2011-01-01

    Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections. PMID:22072905

  19. Recent updates of marine antimicrobial peptides.

    PubMed

    Semreen, Mohammad H; El-Gamal, Mohammed I; Abdin, Shifaa; Alkhazraji, Hajar; Kamal, Leena; Hammad, Saba; El-Awady, Faten; Waleed, Dima; Kourbaj, Layal

    2018-03-01

    Antimicrobial peptides are group of proteins showing broad-spectrum antimicrobial activity that have been known to be powerful agents against a variety of pathogens. This class of compounds contributed to solving the microbial resistance dilemma that limited the use of many potent antimicrobial agents. The marine environment is known to be one of the richest sources for antimicrobial peptides, yet this environment is not fully explored. Hence, the scientific research attention should be directed toward the marine ecosystem as enormous amount of useful discoveries could be brought to the forefront. In the current article, the marine antimicrobial peptides reported from mid 2012 to 2017 have been reviewed.

  20. Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

    PubMed Central

    Costa, Rita; Ferreira-da-Silva, Frederico; Saraiva, Maria J.; Cardoso, Isabel

    2008-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid β-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology. PMID:18682830

  1. Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Li, Mengfei; Yuan, Zhefan; Wu, Dan; Chen, Jia-da; Feng, Jie

    2016-10-01

    A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K10), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K10, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.

  2. Inhibition of Dengue Virus Entry into Target Cells Using Synthetic Antiviral Peptides

    PubMed Central

    Alhoot, Mohammed Abdelfatah; Rathinam, Alwin Kumar; Wang, Seok Mui; Manikam, Rishya; Sekaran, Shamala Devi

    2013-01-01

    Despite the importance of DENV as a human pathogen, there is no specific treatment or protective vaccine. Successful entry into the host cells is necessary for establishing the infection. Recently, the virus entry step has become an attractive therapeutic strategy because it represents a barrier to suppress the onset of the infection. Four putative antiviral peptides were designed to target domain III of DENV-2 E protein using BioMoDroid algorithm. Two peptides showed significant inhibition of DENV when simultaneously incubated as shown by plaque formation assay, RT-qPCR, and Western blot analysis. Both DET4 and DET2 showed significant inhibition of virus entry (84.6% and 40.6% respectively) using micromolar concentrations. Furthermore, the TEM images showed that the inhibitory peptides caused structural abnormalities and alteration of the arrangement of the viral E protein, which interferes with virus binding and entry. Inhibition of DENV entry during the initial stages of infection can potentially reduce the viremia in infected humans resulting in prevention of the progression of dengue fever to the severe life-threatening infection, reduce the infected vector numbers, and thus break the transmission cycle. Moreover these peptides though designed against the conserved region in DENV-2 would have the potential to be active against all the serotypes of dengue and might be considered as Hits to begin designing and developing of more potent analogous peptides that could constitute as promising therapeutic agents for attenuating dengue infection. PMID:23630436

  3. A Trojan-Horse Peptide-Carboxymethyl-Cytidine Antibiotic from Bacillus amyloliquefaciens.

    PubMed

    Serebryakova, Marina; Tsibulskaya, Darya; Mokina, Olga; Kulikovsky, Alexey; Nautiyal, Manesh; Van Aerschot, Arthur; Severinov, Konstantin; Dubiley, Svetlana

    2016-12-07

    Microcin C and related antibiotics are Trojan-horse peptide-adenylates. The peptide part is responsible for facilitated transport inside the sensitive cell, where it gets processed to release a toxic warhead-a nonhydrolyzable aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. Adenylation of peptide precursors is carried out by MccB THIF-type NAD/FAD adenylyltransferases. Here, we describe a novel microcin C-like compound from Bacillus amyloliquefaciens. The B. amyloliquefaciens MccB demonstrates an unprecedented ability to attach a terminal cytidine monophosphate to cognate precursor peptide in cellular and cell free systems. The cytosine moiety undergoes an additional modification-carboxymethylation-that is carried out by the C-terminal domain of MccB and the MccS enzyme that produces carboxy-SAM, which serves as a donor of the carboxymethyl group. We show that microcin C-like compounds carrying terminal cytosines are biologically active and target aspartyl-tRNA synthetase, and that the carboxymethyl group prevents resistance that can occur due to modification of the warhead. The results expand the repertoire of known enzymatic modifications of peptides that can be used to obtain new biological activities while avoiding or limiting bacterial resistance.

  4. Peptide-modified PELCL electrospun membranes for regulation of vascular endothelial cells.

    PubMed

    Zhou, Fang; Jia, Xiaoling; Yang, Yang; Yang, Qingmao; Gao, Chao; Zhao, Yunhui; Fan, Yubo; Yuan, Xiaoyan

    2016-11-01

    The efficiency of biomaterials used in small vascular repair depends greatly on their ability to interact with vascular endothelial cells (VECs). Rapid endothelialization of the vascular grafts is a promising way to prevent thrombosis and intimal hyperplasia. In this work, modification of electrospun membranes of poly(ethylene glycol)-b-poly(l-lactide-co-ε-caprolactone) (PELCL) by three different peptides for regulation of VECs were studied in order to obtain ideal bioactive biomaterials as small diameter vascular grafts. QK (a mimetic peptide to vascular endothelial growth factor), Arg-Glu-Asp-Val (REDV, a specific adhesive peptide to VECs) and Val-Ala-Pro-Gly (VAPG, a specific adhesive peptide to vascular smooth muscle cells) were investigated. Surface properties of the modified membranes and the response of VECs were verified. It was found that protein adsorption and platelet adhesion were effectively suppressed with the introduction of QK, REDV or VAPG peptides on the PELCL electrospun membranes. Both QK- and REDV-modified electrospun membranes could accelerate the proliferation of VECs in the first 9days, and the QK-modified electrospun membrane promoted cell proliferation more significantly than the REDV-modified one. The REDV-modified PELCL membrane was the most favorable for VECs adhesion than QK- and VAPG-modified membranes. It was suggested that QK- or REDV-modified PELCL electrospun membranes may have great potential applications in cardiovascular biomaterials for rapid endothelialization in situ. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Atrial natriuretic peptide stimulates salt secretion by shark rectal gland by releasing VIP

    SciTech Connect

    Silva, P.; Stoff, J.S.; Solomon, R.J.

    1987-01-01

    Salt secretion by the isolated perfused rectal gland of the spiny dogfish shark, Squalus acanthias, is stimulated by synthetic rat atrial natriuretic peptide (ANP II) as well as extracts of shark heart, but not by 8-bromo-cyclic guanosine 5'-monophosphate. Cardiac peptides have no effect on isolated rectal gland cells or perfused tubules, suggesting that stimulation requires an intact gland. The stimulation of secretion by ANP II is eliminated by maneuvers that block neurotransmitter release. Cardiac peptides stimulate the release of vasoactive intestinal peptide (VIP), known to be present in rectal glands nerves, into the venous effluent of perfused glands in parallelmore » with their stimulation of salt secretion, but the release of VIP induced by ANP II is prevented by perfusion with procaine. VIP was measured by radioimmunoassay. Cardiac peptides thus appear to regulate rectal gland secretion by releasing VIP from neural stores within the gland. It is possible that other physiological effects of these hormones might be explained by an action to enhanced local release of neurotransmitters.« less

  6. Long-term physical exercise and atrial natriuretic peptide in obese Zucker rats.

    PubMed

    Pörsti, Ilkka; Kähönen, Mika; Wu, Xiumin; Arvola, Pertti; Ruskoaho, Heikki

    2002-07-01

    Endurance training increases natriuretic peptide synthesis in the hypertrophied myocardium of spontaneously hypertensive rats. We examined the effects of 22-week-long treadmill exercise on plasma and tissue atrial natriuretic peptide in Zucker rats, a model of genetic obesity and moderate hypertension without clear cardiac hypertrophy. The blood pressures of the animals were measured by the tail-cuff method, and plasma and tissue samples for the peptide determinations were taken at the end of the study. The training increased heart weight to body weight ratio, while atrial natriuretic peptide contents in the right and left atrium, ventricular tissue, and plasma did not change. The exercise prevented the elevation of blood pressure, which was observed in non-exercised obese Zucker rats, and also reduced blood pressure in the lean rats. In conclusion, these results suggest that in the absence of preceding myocardial hypertrophy, the long-term exercise-induced workload is not deleterious to the heart in experimental obesity, since no changes in plasma and tissue atrial natriuretic peptide were detected.

  7. A Fusion-Inhibiting Peptide against Rift Valley Fever Virus Inhibits Multiple, Diverse Viruses

    PubMed Central

    Koehler, Jeffrey W.; Smith, Jeffrey M.; Ripoll, Daniel R.; Spik, Kristin W.; Taylor, Shannon L.; Badger, Catherine V.; Grant, Rebecca J.; Ogg, Monica M.; Wallqvist, Anders; Guttieri, Mary C.; Garry, Robert F.; Schmaljohn, Connie S.

    2013-01-01

    For enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. This fusion process is mediated by at least three classes of fusion proteins (Class I, II, and III) based on the protein sequence and structure. For Rift Valley fever virus (RVFV), the glycoprotein Gc (Class II fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. Here, we show that peptides analogous to the RVFV Gc stem region inhibited RVFV infectivity in cell culture by inhibiting the fusion process. Further, we show that infectivity can be inhibited for diverse, unrelated RNA viruses that have Class I (Ebola virus), Class II (Andes virus), or Class III (vesicular stomatitis virus) fusion proteins using this single peptide. Our findings are consistent with an inhibition mechanism similar to that proposed for stem peptide fusion inhibitors of dengue virus in which the RVFV inhibitory peptide first binds to both the virion and cell membranes, allowing it to traffic with the virus into the endocytic pathway. Upon acidification and rearrangement of Gc, the peptide is then able to specifically bind to Gc and prevent fusion of the viral and endocytic membranes, thus inhibiting viral infection. These results could provide novel insights into conserved features among the three classes of viral fusion proteins and offer direction for the future development of broadly active fusion inhibitors. PMID:24069485

  8. Escape from R-peptide deletion in a {gamma}-retrovirus

    SciTech Connect

    Schneider, Irene C.; Eckhardt, Manon; Brynza, Julia

    2011-09-30

    The R peptide in the cytoplasmic tail (C-tail) of {gamma}-retroviral envelope proteins (Env) prevents membrane fusion before budding. To analyse its role in the formation of replication competent, infectious particles, we developed chimeric murine leukaemia viruses (MLV) with unmodified or R-peptide deleted Env proteins of the gibbon ape leukaemia virus (GaLV). While titres of these viruses were unaffected, R-peptide deficiency led to strongly impaired spreading. Most remarkably, we isolated an escape mutant which had restored an open reading frame for a C-terminal extension of the truncated C-tail. A reconstituted virus encoding this escape C-tail replicated in cell culture. In contrastmore » to R-peptide deficient Env, particle incorporation of the escape Env was effective due to an enhanced protein expression and restored intracellular co-localisation with Gag proteins. Our data demonstrate that the R peptide not only regulates membrane fusion but also mediates efficient Env protein particle incorporation in {gamma}-retrovirus infected cells.« less

  9. Surface modification and properties of Bombyx mori silk fibroin films by antimicrobial peptide

    NASA Astrophysics Data System (ADS)

    Bai, Liqiang; Zhu, Liangjun; Min, Sijia; Liu, Lin; Cai, Yurong; Yao, Juming

    2008-03-01

    The Bombyx mori silk fibroin films (SFFs) were modified by a Cecropin B ( CB) antimicrobial peptide, (NH 2)-NGIVKAGPAIAVLGEAAL-CONH 2, using the carbodiimide chemistry method. In order to avoid the dissolution of films during the modification procedure, the SFFs were first treated with 60% (v/v) ethanol aqueous solution, resulting a structural transition from unstable silk I to silk II. The investigation of modification conditions showed that the surface-modified SFFs had the satisfied antimicrobial activity and durability when they were activated by EDC·HCl/NHS solution followed by a treatment in CB peptide/PBS buffer (pH 6.5 or 8) solution at ambient temperature for 2 h. Moreover, the surface-modified SFFs showed the smaller contact angle due to the hydrophilic antimicrobial peptides coupled on the film surface, which is essential for the cell adhesion and proliferation. AFM results indicated that the surface roughness of SFFs was considerably increased after the modification by the peptides. The elemental composition analysis results also suggested that the peptides were tightly coupled to the surface of SFFs. This approach may provide a new option to engineer the surface-modified implanted materials preventing the biomaterial-centered infection (BCI).

  10. Pharmacologic Effects in vivo in Brain by Vector-Mediated Peptide Drug Delivery

    NASA Astrophysics Data System (ADS)

    Bickel, Ulrich; Yoshikawa, Takayoshi; Landaw, Elliot M.; Faull, Kym F.; Pardridge, William M.

    1993-04-01

    Pharmacologic effects in brain caused by systemic administration of neuropeptides are prevented by poor transport of the peptide through the brain vascular endothelium, which comprises the blood-brain barrier in vivo. In the present study, successful application of a chimeric peptide approach to enhance drug delivery through the blood-brain barrier for the purpose of achieving a central nervous system pharmacologic effect is described. The chimeric peptide was formed by linkage of a potent vasoactive intestinal peptide (VIP) analogue, which had been monobiotinylated, to a drug transport vector. The vector consisted of a covalent conjugate of avidin and the OX26 monoclonal antibody to the transferrin receptor. Owing to the high concentration of transferrin receptors on brain capillary endothelia, OX26 targets brain and undergoes receptor-mediated transcytosis through the blood-brain barrier. Systemic infusion of low doses (12 μg/kg) of the VIP chimeric peptide in rats resulted in an in vivo central nervous system pharmacologic effect: a 65% increase in cerebral blood flow. Biotinylated VIP analogue without the brain transport vector was ineffective.

  11. Chlorella 11-Peptide Inhibits the Production of Macrophage-Induced Adhesion Molecules and Reduces Endothelin-1 Expression and Endothelial Permeability

    PubMed Central

    Shih, Mei Fen; Chen, Lih Chi; Cherng, Jong Yuh

    2013-01-01

    The inflammation process in large vessels involves the up-regulation of vascular adhesion molecules such as endothelial cell selectin (E-selectin), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) which are also known as the markers of atherosclerosis. We have reported that Chlorella 11-peptide exhibited effective anti-inflammatory effects. This peptide with an amino sequence Val-Glu-Cys-Tyr-Gly-Pro-Asn-Arg-Pro-Gln-Phe was further examined for its potential in preventing atherosclerosis in this study. In particular, the roles of Chlorella 11-peptide in lowering the production of vascular adhesion molecules, monocyte chemoattractant protein (MCP-1) and expression of endothelin-1 (ET-1) from endothelia (SVEC4-10 cells) were studied. The production of E-selectin, ICAM-1, VCAM-1 and MCP-1 in SVEC4-10 cells was measured with ELISA. The mRNA expression of ET-1 was analyzed by RT-PCR and agarose gel. Results showed that Chlorella 11-peptide significantly suppressed the levels of E-selectin, ICAM, VCAM, MCP-1 as well as ET-1 gene expression. The inhibition of ICAM-1 and VCAM-1 production by Chlorella 11-peptide was reversed in the presence of protein kinase A inhibitor (H89) which suggests that the cAMP pathway was involved in the inhibitory cause of the peptide. In addition, this peptide was shown to reduce the extent of increased intercellular permeability induced by combination of 50% of lipopolysaccharide (LPS)-activated RAW 264.7 cells medium and 50% normal SEVC cell culture medium (referred to as 50% RAW-conditioned medium). These data demonstrate that Chlorella 11-peptide is a promising biomolecule in preventing chronic inflammatory-related vascular diseases. PMID:24129228

  12. Amide I SFG Spectral Line Width Probes the Lipid-Peptide and Peptide-Peptide Interactions at Cell Membrane In Situ and in Real Time.

    PubMed

    Zhang, Baixiong; Tan, Junjun; Li, Chuanzhao; Zhang, Jiahui; Ye, Shuji

    2018-06-13

    The balance of lipid-peptide and peptide-peptide interactions at cell membrane is essential to a large variety of cellular processes. In this study, we have experimentally demonstrated for the first time that sum frequency generation vibrational spectroscopy can be used to probe the peptide-peptide and lipid-peptide interactions in cell membrane in situ and in real time by determination of the line width of amide I band of protein backbone. Using a "benchmark" model of α-helical WALP23, it is found that the dominated lipid-peptide interaction causes a narrow line width of the amide I band, whereas the peptide-peptide interaction can markedly broaden the line width. When WALP23 molecules insert into the lipid bilayer, a quite narrow line width of the amide I band is observed because of the lipid-peptide interaction. In contrast, when the peptide lies down on the bilayer surface, the line width of amide I band becomes very broad owing to the peptide-peptide interaction. In terms of the real-time change in the line width, the transition from peptide-peptide interaction to lipid-peptide interaction is monitored during the insertion of WALP23 into 1,2-dipalmitoyl- sn-glycero-3-phospho-(1'- rac-glycerol) (DPPG) lipid bilayer. The dephasing time of a pure α-helical WALP23 in 1-palmitoyl-2-oleoyl- sn-glycero-3-phospho-(1'- rac-glycerol) and DPPG bilayer is determined to be 2.2 and 0.64 ps, respectively. The peptide-peptide interaction can largely accelerate the dephasing time.

  13. C-Peptide Is a Sensitive Indicator for the Diagnosis of Metabolic Syndrome in Subjects from Central Mexico.

    PubMed

    Gonzalez-Mejia, M Elba; Porchia, Leonardo M; Torres-Rasgado, Enrique; Ruiz-Vivanco, Guadalupe; Pulido-Pérez, Patricia; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2016-05-01

    Metabolic Syndrome (MetS) is associated with elevated risk for developing diabetes and cardiovascular disease. A key component of MetS is the development of insulin resistance (IR). The homeostatic model assessment (HOMA) model can determine IR by using insulin or C-peptide concentrations; however, the efficiency of insulin and C-peptide to determine MetS has not been compared. The aim of the study was to compare the efficiency of C-peptide and insulin to determine MetS in Mexicans. Anthropometrics, glucose, insulin, C-peptide, triglycerides, and high-density lipoproteins were determined in 156 nonpregnant females and 114 males. Subjects were separated into normal or positive for MetS. IR was determined by the HOMA2 calculator using insulin or C-peptide. Correlations were calculated using the Spearman correlation coefficient (ρ). Differences between correlations were determined by calculating Steiger's Z. The sensitivity was determined by the area under receiver operating characteristics curve (AUC) analysis. Independent of the MetS definition [Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF), or World Health Organization (WHO)], C-peptide and insulin were significantly higher in MetS subjects (P < 0.05). C-peptide and insulin correlated with all components of MetS; however, for waist circumference, waist-to-hip ratio, and fasting plasma glucose, C-peptide correlated better than insulin (P < 0.05). Moreover, C-peptide (AUC = 0.72-0.78) was a better marker than insulin (AUC = 0.62-0.72) for MetS (P < 0.05). Finally, HOMA2-IR calculated with C-peptide (AUC = 0.80-0.84) was more accurate than HOMA2-IR calculated with insulin (AUC = 0.68-0.75, P < 0.05) at determining MetS. C-peptide is a strong indicator of MetS. Since C-peptide has recently emerged as a biomolecule with significant importance for inflammatory diseases, monitoring C-peptide levels will aid clinicians in preventing MetS.

  14. Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections

    PubMed Central

    Findlay, Fern; Proudfoot, Lorna; Stevens, Craig

    2016-01-01

    Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required. PMID:27315342

  15. Cationic host defense peptides; novel antimicrobial therapeutics against Category A pathogens and emerging infections.

    PubMed

    Findlay, Fern; Proudfoot, Lorna; Stevens, Craig; Barlow, Peter G

    2016-01-01

    Cationic Host Defense Peptides (HDP, also known as antimicrobial peptides) are crucial components of the innate immune system and possess broad-spectrum antibacterial, antiviral, and immunomodulatory activities. They can contribute to the rapid clearance of biological agents through direct killing of the organisms, inhibition of pro-inflammatory mediators such as lipopolysaccharide, and by modulating the inflammatory response to infection. Category A biological agents and materials, as classified by the United States National Institutes for Health, the US Centers for Disease Control and Prevention, and the US Department of Homeland Security, carry the most severe threat in terms of human health, transmissibility, and preparedness. As such, there is a pressing need for novel frontline approaches for prevention and treatment of diseases caused by these organisms, and exploiting the broad antimicrobial activity exhibited by cationic host defense peptides represents an exciting priority area for clinical research. This review will summarize what is known about the antimicrobial and antiviral effects of the two main families of cationic host defense peptides, cathelicidins, and defensins in the context of Category A biological agents which include, but are not limited to; anthrax (Bacillus anthracis), plague (Yersinia pestis), smallpox (Variola major), tularemia (Francisella tularensis). In addition, we highlight priority areas, particularly emerging viral infections, where more extensive research is urgently required.

  16. Mitochondria targeted peptides protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity.

    PubMed

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y; Luo, Guoxiong; Szeto, Hazel H; Beal, M Flint

    2009-09-01

    A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD.

  17. Molecular targets of antihypertensive peptides: understanding the mechanisms of action based on the pathophysiology of hypertension.

    PubMed

    Majumder, Kaustav; Wu, Jianping

    2014-12-24

    There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides.

  18. Molecular Targets of Antihypertensive Peptides: Understanding the Mechanisms of Action Based on the Pathophysiology of Hypertension

    PubMed Central

    Majumder, Kaustav; Wu, Jianping

    2014-01-01

    There is growing interest in using functional foods or nutraceuticals for the prevention and treatment of hypertension or high blood pressure. Although numerous preventive and therapeutic pharmacological interventions are available on the market, unfortunately, many patients still suffer from poorly controlled hypertension. Furthermore, most pharmacological drugs, such as inhibitors of angiotensin-I converting enzyme (ACE), are often associated with significant adverse effects. Many bioactive food compounds have been characterized over the past decades that may contribute to the management of hypertension; for example, bioactive peptides derived from various food proteins with antihypertensive properties have gained a great deal of attention. Some of these peptides have exhibited potent in vivo antihypertensive activity in both animal models and human clinical trials. This review provides an overview about the complex pathophysiology of hypertension and demonstrates the potential roles of food derived bioactive peptides as viable interventions targeting specific pathways involved in this disease process. This review offers a comprehensive guide for understanding and utilizing the molecular mechanisms of antihypertensive actions of food protein derived peptides. PMID:25547491

  19. Simulation of Peptides at Aqueous Interfaces

    NASA Technical Reports Server (NTRS)

    Pohorille, Andrew; Wilson, M.; Chipot, C.; DeVincenzi, Donald L. (Technical Monitor)

    2001-01-01

    Behavior of peptides at water-membrane interfaces is of great interest in studies on cellular transport and signaling, membrane fusion, and the action of toxins and antibiotics. Many peptides, which exist in water only as random coils, can form sequence-dependent, ordered structures at aqueous interfaces, incorporate into membranes and self-assembly into functional units, such as simple ion channels. Multi -nanosecond molecular dynamics simulations have been carried out to study the mechanism and energetics of interfacial folding of both non-polar and amphiphilic peptides, their insertion into membranes and association into higher-order structures. The simulations indicate that peptides fold non-sequentially, often through a series of amphiphilic intermediates. They further incorporate into the membrane in a preferred direction as folded monomers, and only then aggregate into dimers and, possibly, further into "dimers of dimers".

  20. Natriuretic Peptides as Biomarkers in Heart Failure

    PubMed Central

    Januzzi, James L.

    2014-01-01

    Following the initial discovery of a natriuretic and diuretic peptide factor present in atrial myocardial tissue homogenates, subsequent elucidation of the natriuretic peptide family has led to substantial advances in the understanding of the autocrine, paracrine, and endocrine regulation of the cardiovascular system. Furthermore, with the development of assays for the measurement of the natriuretic peptides, these important biomarkers have gone from being regarded as biological mediators of the cardiovascular system to now represent important clinical tools for the diagnostic and prognostic evaluation of patients with heart failure, and may have potential as a therapeutic target in this setting as well. An historical perspective on the natriuretic peptides from bench to bedside translation will be discussed. PMID:23661103

  1. Biologically Active and Antimicrobial Peptides from Plants

    PubMed Central

    Salas, Carlos E.; Badillo-Corona, Jesus A.; Ramírez-Sotelo, Guadalupe; Oliver-Salvador, Carmen

    2015-01-01

    Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application. PMID:25815307

  2. Advances in synthetic peptides reagent discovery

    NASA Astrophysics Data System (ADS)

    Adams, Bryn L.; Sarkes, Deborah A.; Finch, Amethist S.; Stratis-Cullum, Dimitra N.

    2013-05-01

    Bacterial display technology offers a number of advantages over competing display technologies (e.g, phage) for the rapid discovery and development of peptides with interaction targeted to materials ranging from biological hazards through inorganic metals. We have previously shown that discovery of synthetic peptide reagents utilizing bacterial display technology is relatively simple and rapid to make laboratory automation possible. This included extensive study of the protective antigen system of Bacillus anthracis, including development of discovery, characterization, and computational biology capabilities for in-silico optimization. Although the benefits towards CBD goals are evident, the impact is far-reaching due to our ability to understand and harness peptide interactions that are ultimately extendable to the hybrid biomaterials of the future. In this paper, we describe advances in peptide discovery including, new target systems (e.g. non-biological materials), advanced library development and clone analysis including integrated reporting.

  3. Retardation of ice crystallization by short peptides

    NASA Astrophysics Data System (ADS)

    Kim, Jun Soo; Yethiraj, Arun

    2009-03-01

    The effect of short peptides on the growth of ice crystals is studied using molecular dynamics simulations. The simulations focus on two sequences (Gly-Pro-Ala-Gly and Gly-Gly-Ala-Gly) that are found in collagen hydrolysate, a substance that is known to retard crystal growth. In the absence of peptides, the growth of ice crystal in the solution with the ice/water interface is observed in at a rate comparable to the experimental data. When peptides are present in the liquid phase, the crystal growth is retarded to a significant extent compared to the pure water. It is found that Gly-Pro-Ala-Gly is more effective (crystallization is up to 5 times slower than in its absence) than Gly-Gly-Ala-Gly (up to 3 times slower) implying that the role of the proline residue is important. The mechanism can be understood in the nature of binding of the peptides to the growing crystal.

  4. Functional peptides for cartilage repair and regeneration

    PubMed Central

    Liu, Qisong; Jia, Zhaofeng; Duan, Li; Xiong, Jianyi; Wang, Daping; Ding, Yue

    2018-01-01

    Cartilage repair after degeneration or trauma continues to be a challenge both in the clinic and for scientific research due to the limited regenerative capacity of this tissue. Cartilage tissue engineering, involving a combination of cells, scaffolds, and growth factors, is increasingly used in cartilage regeneration. Due to their ease of synthesis, robustness, tunable size, availability of functional groups, and activity, peptides have emerged as the molecules with the most potential in drug development. A number of peptides have been engineered to regenerate cartilage by acting as scaffolds, functional molecules, or both. In this paper, we will summarize the application of peptides in cartilage tissue engineering and discuss additional possibilities for peptides in this field. PMID:29511444

  5. Peptide Seems to Boost Human Memory.

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1981

    1981-01-01

    This article discusses recent studies which have shown that the peptide hormone vasopressin apparently can stimulate memory and learning in healthy human volunteers and in certain mentally disturbed patients. (ECO)

  6. CART PEPTIDE IN THE NUCLEUS ACCUMBENS REGULATES PSYCHOSTIMULANTS: CORRELATIONS BETWEEN PSYCHOSTIMULANT AND CART PEPTIDE EFFECTS

    PubMed Central

    JOB, MARTIN O.; KUHAR, MICHAEL J.

    2017-01-01

    In this study, we reexamined the effect of CART peptide on psychostimulant (PS)-induced locomotor activity (LMA) in individual rats. The Methods utilized were as previously published. The PS-induced LMA was defined as the distance traveled after PS administration (intraperitoneal), and the CART peptide effect was defined as the change in the PS-induced activity after bilateral intra-NAc administration of CART peptide. The experiments included both male and female Sprague-Dawley rats, and varying the CART peptide dose and the PS dose. While the average effect of CART peptide was to inhibit PS-induced LMA, the effect of CART peptide on individual PS treated animals was not always inhibitory and sometimes even produced an increase or no change in PS-induced LMA. Upon further analysis, we observed a linear correlation, reported for the first time, between the magnitude of PS-induced LMA and the CART peptide effect. Because CART peptide inhibits PS-induced LMA when it is large, and increases PS-induced LMA when it is small, the peptide can be considered a homeostatic regulator of dopamine (DA)-induced LMA, which supports our earlier homeostatic hypothesis. PMID:28215744

  7. In silico optimization of a guava antimicrobial peptide enables combinatorial exploration for peptide design.

    PubMed

    Porto, William F; Irazazabal, Luz; Alves, Eliane S F; Ribeiro, Suzana M; Matos, Carolina O; Pires, Állan S; Fensterseifer, Isabel C M; Miranda, Vivian J; Haney, Evan F; Humblot, Vincent; Torres, Marcelo D T; Hancock, Robert E W; Liao, Luciano M; Ladram, Ali; Lu, Timothy K; de la Fuente-Nunez, Cesar; Franco, Octavio L

    2018-04-16

    Plants are extensively used in traditional medicine, and several plant antimicrobial peptides have been described as potential alternatives to conventional antibiotics. However, after more than four decades of research no plant antimicrobial peptide is currently used for treating bacterial infections, due to their length, post-translational modifications or  high dose requirement for a therapeutic effect . Here we report the design of antimicrobial peptides derived from a guava glycine-rich peptide using a genetic algorithm. This approach yields guavanin peptides, arginine-rich α-helical peptides that possess an unusual hydrophobic counterpart mainly composed of tyrosine residues. Guavanin 2 is characterized as a prototype peptide in terms of structure and activity. Nuclear magnetic resonance analysis indicates that the peptide adopts an α-helical structure in hydrophobic environments. Guavanin 2 is bactericidal at low concentrations, causing membrane disruption and triggering hyperpolarization. This computational approach for the exploration of natural products could be used to design effective peptide antibiotics.

  8. Systematic Errors in Peptide and Protein Identification and Quantification by Modified Peptides*

    PubMed Central

    Bogdanow, Boris; Zauber, Henrik; Selbach, Matthias

    2016-01-01

    The principle of shotgun proteomics is to use peptide mass spectra in order to identify corresponding sequences in a protein database. The quality of peptide and protein identification and quantification critically depends on the sensitivity and specificity of this assignment process. Many peptides in proteomic samples carry biochemical modifications, and a large fraction of unassigned spectra arise from modified peptides. Spectra derived from modified peptides can erroneously be assigned to wrong amino acid sequences. However, the impact of this problem on proteomic data has not yet been investigated systematically. Here we use combinations of different database searches to show that modified peptides can be responsible for 20–50% of false positive identifications in deep proteomic data sets. These false positive hits are particularly problematic as they have significantly higher scores and higher intensities than other false positive matches. Furthermore, these wrong peptide assignments lead to hundreds of false protein identifications and systematic biases in protein quantification. We devise a “cleaned search” strategy to address this problem and show that this considerably improves the sensitivity and specificity of proteomic data. In summary, we show that modified peptides cause systematic errors in peptide and protein identification and quantification and should therefore be considered to further improve the quality of proteomic data annotation. PMID:27215553

  9. Expression of the cationic antimicrobial peptide lactoferricin fused with the anionic peptide in Escherichia coli.

    PubMed

    Kim, Ha-Kun; Chun, Dae-Sik; Kim, Joon-Sik; Yun, Cheol-Ho; Lee, Ju-Hoon; Hong, Soon-Kwang; Kang, Dae-Kyung

    2006-09-01

    Direct expression of lactoferricin, an antimicrobial peptide, is lethal to Escherichia coli. For the efficient production of lactoferricin in E. coli, we developed an expression system in which the gene for the lysine- and arginine-rich cationic lactoferricin was fused to an anionic peptide gene to neutralize the basic property of lactoferricin, and successfully overexpressed the concatemeric fusion gene in E. coli. The lactoferricin gene was linked to a modified magainin intervening sequence gene by a recombinational polymerase chain reaction, thus producing an acidic peptide-lactoferricin fusion gene. The monomeric acidic peptide-lactoferricin fusion gene was multimerized and expressed in E. coli BL21(DE3) upon induction with isopropyl-beta-D-thiogalactopyranoside. The expression levels of the fusion peptide reached the maximum at the tetramer, while further increases in the copy number of the fusion gene substantially reduced the peptide expression level. The fusion peptides were isolated and cleaved to generate the separate lactoferricin and acidic peptide. About 60 mg of pure recombinant lactoferricin was obtained from 1 L of E. coli culture. The purified recombinant lactoferricin was found to have a molecular weight similar to that of chemically synthesized lactoferricin. The recombinant lactoferricin showed antimicrobial activity and disrupted bacterial membrane permeability, as the native lactoferricin peptide does.

  10. Computational Framework for Prediction of Peptide Sequences That May Mediate Multiple Protein Interactions in Cancer-Associated Hub Proteins.

    PubMed

    Sarkar, Debasree; Patra, Piya; Ghosh, Abhirupa; Saha, Sudipto

    2016-01-01

    A considerable proportion of protein-protein interactions (PPIs) in the cell are estimated to be mediated by very short peptide segments that approximately conform to specific sequence patterns known as linear motifs (LMs), often present in the disordered regions in the eukaryotic proteins. These peptides have been found to interact with low affinity and are able bind to multiple interactors, thus playing an important role in the PPI networks involving date hubs. In this work, PPI data and de novo motif identification based method (MEME) were used to identify such peptides in three cancer-associated hub proteins-MYC, APC and MDM2. The peptides corresponding to the significant LMs identified for each hub protein were aligned, the overlapping regions across these peptides being termed as overlapping linear peptides (OLPs). These OLPs were thus predicted to be responsible for multiple PPIs of the corresponding hub proteins and a scoring system was developed to rank them. We predicted six OLPs in MYC and five OLPs in MDM2 that scored higher than OLP predictions from randomly generated protein sets. Two OLP sequences from the C-terminal of MYC were predicted to bind with FBXW7, component of an E3 ubiquitin-protein ligase complex involved in proteasomal degradation of MYC. Similarly, we identified peptides in the C-terminal of MDM2 interacting with FKBP3, which has a specific role in auto-ubiquitinylation of MDM2. The peptide sequences predicted in MYC and MDM2 look promising for designing orthosteric inhibitors against possible disease-associated PPIs. Since these OLPs can interact with other proteins as well, these inhibitors should be specific to the targeted interactor to prevent undesired side-effects. This computational framework has been designed to predict and rank the peptide regions that may mediate multiple PPIs and can be applied to other disease-associated date hub proteins for prediction of novel therapeutic targets of small molecule PPI modulators.

  11. Bullying Prevention

    ERIC Educational Resources Information Center

    Kemp, Patrice

    2016-01-01

    The focus of the milestone project is to focus on bridging the gap of bullying and classroom instruction methods. There has to be a defined expectations and level of accountability that has to be defined when supporting and implementing a plan linked to bullying prevention. All individuals involved in the student's learning have to be aware of…

  12. Injury Prevention

    MedlinePlus

    ... Children Swallowing Objects Like Magnets, Coins or Batteries School & Sports Injuries Safety Helmets Save Lives, Prevent Traumatic Brain Injury School sports Injuries can land students in the ER. Text Messaging: Emergency Physicians Express Safety Concerns As Kids Go Back To School Think ...

  13. Labeled Antimicrobial Peptides for Detection of Microorganisms

    DTIC Science & Technology

    2008-12-01

    1. INTRODUCTION Antimicrobial peptides (AMPs) are part of the innate defense system found in all organisms to protect them from microbial infection...2005) with antimicrobial activity against predominantly gram-negative bacteria. SMAP29 is from the cathelicidin family of peptides found in sheep ...in buffer, milk and apple juice. Cells were grown and prepared in PBST as described above. 20 III anti-£. coli 0157 paramagnetic Dyna-beads (Dynal

  14. Antimicrobial Peptides with Differential Bacterial Binding Characteristics

    DTIC Science & Technology

    2013-03-01

    Each well was incubated with 150 µL 0.2% non- fat dried milk in PBS (pH 7.2) for 30 min without agitation to block any remaining active sites...Conference [1], a book chapter in Microbial Surfaces: Structure, Interactions, and Reactivity [2], and two peer-review manuscripts, one in Protein & Peptide...book chapter in Microbial Surfaces: Structure, Interactions, and Reactivity [2], Protein and Peptide Letters [3], and Colloids and Surfaces B

  15. Libraries of Peptide Fragmentation Mass Spectra Database

    National Institute of Standards and Technology Data Gateway

    SRD 1C NIST Libraries of Peptide Fragmentation Mass Spectra Database (Web, free access)   The purpose of the library is to provide peptide reference data for laboratories employing mass spectrometry-based proteomics methods for protein analysis. Mass spectral libraries identify these compounds in a more sensitive and robust manner than alternative methods. These databases are freely available for testing and development of new applications.

  16. HLA-F: A New Kid Licensed for Peptide Presentation.

    PubMed

    Sim, Malcolm J W; Sun, Peter D

    2017-06-20

    HLA-F, a non-classical MHC molecule, is not known to present peptides. Dulberger et al. (2017) show that HLA-F contains a distinct peptide-binding groove and can present a diverse array of peptides. LIR1, however, recognized HLA-F away from bound peptide, leaving open whether peptide-HLA-F-specific T and NK receptors exist. Published by Elsevier Inc.

  17. Recombinant Peptides as Biomarkers for Metastatic Breast Cancer Response

    DTIC Science & Technology

    2007-10-01

    could be specific to breast cancer tumor models has just been concluded. In vivo biopanning wsa conducted with a T7 phage -based random peptide library...peptides selected from phage -displayed libraries. 15. SUBJECT TERMS Breast cancer, phage display, molecular imaging, personalized medicine 16...recombinant peptides from phage -displayed peptide libraries can be selected that bind to receptors activated in response to therapy. These peptides in turn

  18. Combinatorial contextualization of peptidic epitopes for enhanced cellular immunity.

    PubMed

    Ito, Masaki; Hayashi, Kazumi; Adachi, Eru; Minamisawa, Tamiko; Homma, Sadamu; Koido, Shigeo; Shiba, Kiyotaka

    2014-01-01

    Invocation of cellular immunity by epitopic peptides remains largely dependent on empirically developed protocols, such as interfusion of aluminum salts or emulsification using terpenoids and surfactants. To explore novel vaccine formulation, epitopic peptide motifs were co-programmed with structural motifs to produce artificial antigens using our "motif-programming" approach. As a proof of concept, we used an ovalbumin (OVA) system and prepared an artificial protein library by combinatorially polymerizing MHC class I and II sequences from OVA along with a sequence that tends to form secondary structures. The purified endotoxin-free proteins were then examined for their ability to activate OVA-specific T-cell hybridoma cells after being processed within dendritic cells. One clone, F37A (containing three MHC I and two MHC II OVA epitopes), possessed a greater ability to evoke cellular immunity than the native OVA or the other artificial antigens. The sensitivity profiles of drugs that interfered with the F37A uptake differed from those of the other artificial proteins and OVA, suggesting that alteration of the cross-presentation pathway is responsible for the enhanced immunogenicity. Moreover, F37A, but not an epitopic peptide, invoked cellular immunity when injected together with monophosphoryl lipid A (MPL), and retarded tumor growth in mice. Thus, an artificially synthesized protein antigen induced cellular immunity in vivo in the absence of incomplete Freund's adjuvant or aluminum salts. The method described here could be potentially used for developing vaccines for such intractable ailments as AIDS, malaria and cancer, ailments in which cellular immunity likely play a crucial role in prevention and treatment.

  19. Role of stress peptides during human pregnancy and labour.

    PubMed

    Hillhouse, Edward W; Grammatopoulos, Dimitris K

    2002-09-01

    Premature birth is the major source of perinatal death and disability. Furthermore, the intrauterine health of the baby is important for preventing certain adult diseases. However, the molecular mechanisms driving the onset of human labour remain uncertain, although several key players have been identified. It is becoming clear that there are many pathways to parturition in humans. Stress peptides, in particular placental corticotrophin releasing hormone (CRH) and possibly the related peptide urocortin, appear to play important roles throughout pregnancy. Plasma CRH is a predictor of the duration of human gestation. During most of pregnancy, CRH, acting via specific CRH receptor subtypes, plays a 'protective' role by promoting myometrial quiescence via the generation of cAMP and cGMP, and upregulation of nitric oxide synthase expression. At term, myometrial contractility is enhanced by a complex series of molecular switches, involving the upregulation of oxytocin receptor expression and crosstalk between the oxytocin and CRH receptors. This results in protein kinase C-induced phosphorylation of specific CRH receptor subtypes, with subsequent desensitization and a shift in the intracellular microenvironment to enhance contractility. CRH/urocortin, via specific receptor isoforms, is now able to activate Gq and potentially enhance the oxytocin-driven generation of inositol triphosphate. In addition, CRH/urocortin, via specific CRH receptor subtypes, may generate prostaglandins from the fetal membranes and decidua, play a role in placental vasodilatation and participate in fetal adrenal function and organ maturation. These peptides and receptors are phylogenetically ancient and well preserved across species. They may have evolved as a mechanism to protect against the 'stress' of premature birth.

  20. Confinement-Dependent Friction in Peptide Bundles

    PubMed Central

    Erbaş, Aykut; Netz, Roland R.

    2013-01-01

    Friction within globular proteins or between adhering macromolecules crucially determines the kinetics of protein folding, the formation, and the relaxation of self-assembled molecular systems. One fundamental question is how these friction effects depend on the local environment and in particular on the presence of water. In this model study, we use fully atomistic MD simulations with explicit water to obtain friction forces as a single polyglycine peptide chain is pulled out of a bundle of k adhering parallel polyglycine peptide chains. The whole system is periodically replicated along the peptide axes, so a stationary state at prescribed mean sliding velocity V is achieved. The aggregation number is varied between k = 2 (two peptide chains adhering to each other with plenty of water present at the adhesion sites) and k = 7 (one peptide chain pulled out from a close-packed cylindrical array of six neighboring peptide chains with no water inside the bundle). The friction coefficient per hydrogen bond, extrapolated to the viscous limit of vanishing pulling velocity V → 0, exhibits an increase by five orders of magnitude when going from k = 2 to k = 7. This dramatic confinement-induced friction enhancement we argue to be due to a combination of water depletion and increased hydrogen-bond cooperativity. PMID:23528088

  1. Encrypted Antimicrobial Peptides from Plant Proteins.

    PubMed

    Ramada, M H S; Brand, G D; Abrão, F Y; Oliveira, M; Filho, J L Cardozo; Galbieri, R; Gramacho, K P; Prates, M V; Bloch, C

    2017-10-16

    Examples of bioactive peptides derived from internal sequences of proteins are known for decades. The great majority of these findings appear to be fortuitous rather than the result of a deliberate and methodological-based enterprise. In the present work, we describe the identification and the biological activities of novel antimicrobial peptides unveiled as internal fragments of various plant proteins founded on our hypothesis-driven search strategy. All putative encrypted antimicrobial peptides were selected based upon their physicochemical properties that were iteratively selected by an in-house computer program named Kamal. The selected peptides were chemically synthesized and evaluated for their interaction with model membranes. Sixteen of these peptides showed antimicrobial activity against human and/or plant pathogens, some with a wide spectrum of activity presenting similar or superior inhibition efficacy when compared to classical antimicrobial peptides (AMPs). These original and previously unforeseen molecules constitute a broader and undisputable set of evidences produced by our group that illustrate how the intragenic concept is a workable reality and should be carefully explored not only for microbicidal agents but also for many other biological functions.

  2. Driving reproduction: RFamide peptides behind the wheel.

    PubMed

    Kriegsfeld, Lance J

    2006-12-01

    The availability of tools for probing the genome and proteome more efficiently has allowed for the rapid discovery of novel genes and peptides that play important, previously uncharacterized roles in neuroendocrine regulation. In this review, the role of a class of neuropeptides containing the C-terminal Arg-Phe-NH(2) (RFamide) in regulating the reproductive axis will be highlighted. Neuropeptides containing the C-terminal Phe-Met-Arg-Phe-NH(2) (FMRFamide) were first identified as cardioregulatory elements in the bi-valve mollusk Macrocallista nimbosa. During the past two decades, numerous studies have shown the presence of structurally similar peptides sharing the RFamide motif across taxa. In vertebrates, RFamide peptides have pronounced influences on opiatergic regulation and neuroendocrine function. Two key peptides in this family are emerging as important regulators of the reproductive axis, kisspeptin and gonadotropin-inhibitory hormone (GnIH). Kisspeptin acts as the accelerator, directly driving gonadotropin-releasing hormone (GnRH) neurons, whereas GnIH acts as the restraint. Recent evidence suggests that both peptides play a role in mediating the negative feedback effects of sex steroids. This review presents the hypothesis that these peptides share complementary roles by responding to internal and external stimuli with opposing actions to precisely regulate the reproductive axis.

  3. Driving Reproduction: RFamide Peptides Behind the Wheel

    PubMed Central

    Kriegsfeld, Lance J.

    2012-01-01

    The availability of tools for probing the genome and proteome more efficiently has allowed for the rapid discovery of novel genes and peptides that play important, previously-uncharacterized roles in neuroendocrine regulation. In this review, the role of a class of neuropeptides containing the C-terminal Arg-Phe-NH2 (RFamide) in regulating the reproductive axis will be highlighted. Neuropeptides containing the C-terminal Phe- Met-Arg-Phe-NH2 (FMRFamide) were first identified as cardioregulatory elements in the bi-valve mollusk, Macrocallista nimbosa. During the past two decades, numerous studies have shown the presence of structurally-similar peptides sharing the RFamide motif across taxa. In vertebrates, RFamide peptides have pronounced influences on opiatergic regulation and neuroendocrine function. Two key peptides in this family are emerging as important regulators of the reproductive axis, kisspeptin and gonadotropin-inhibitory hormone (GnIH). Kisspeptin acts as the accelerator, directly driving gonadotropin-releasing hormone (GnRH) neurons, whereas GnIH acts as the restraint. Recent evidence suggests that both peptides play a role in mediating the negative feedback effects of sex steroids. This review presents the hypothesis that these peptides share complementary roles by responding to internal and external stimuli with opposing actions to precisely regulate the reproductive axis. PMID:16876801

  4. Designing Anticancer Peptides by Constructive Machine Learning.

    PubMed

    Grisoni, Francesca; Neuhaus, Claudia S; Gabernet, Gisela; Müller, Alex T; Hiss, Jan A; Schneider, Gisbert

    2018-04-21

    Constructive (generative) machine learning enables the automated generation of novel chemical structures without the need for explicit molecular design rules. This study presents the experimental application of such a deep machine learning model to design membranolytic anticancer peptides (ACPs) de novo. A recurrent neural network with long short-term memory cells was trained on α-helical cationic amphipathic peptide sequences and then fine-tuned with 26 known ACPs by transfer learning. This optimized model was used to generate unique and novel amino acid sequences. Twelve of the peptides were synthesized and tested for their activity on MCF7 human breast adenocarcinoma cells and selectivity against human erythrocytes. Ten of these peptides were active against cancer cells. Six of the active peptides killed MCF7 cancer cells without affecting human erythrocytes with at least threefold selectivity. These results advocate constructive machine learning for the automated design of peptides with desired biological activities. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Protein quantification using a cleavable reporter peptide.

    PubMed

    Duriez, Elodie; Trevisiol, Stephane; Domon, Bruno

    2015-02-06

    Peptide and protein quantification based on isotope dilution and mass spectrometry analysis are widely employed for the measurement of biomarkers and in system biology applications. The accuracy and reliability of such quantitative assays depend on the quality of the stable-isotope labeled standards. Although the quantification using stable-isotope labeled peptides is precise, the accuracy of the results can be severely biased by the purity of the internal standards, their stability and formulation, and the determination of their concentration. Here we describe a rapid and cost-efficient method to recalibrate stable isotope labeled peptides in a single LC-MS analysis. The method is based on the equimolar release of a protein reference peptide (used as surrogate for the protein of interest) and a universal reporter peptide during the trypsinization of a concatenated polypeptide standard. The quality and accuracy of data generated with such concatenated polypeptide standards are highlighted by the quantification of two clinically important proteins in urine samples and compared with results obtained with conventional stable isotope labeled reference peptides. Furthermore, the application of the UCRP standards in complex samples is described.

  6. Peptides with Dual Antimicrobial and Anticancer Activities

    NASA Astrophysics Data System (ADS)

    Felício, Mário R.; Silva, Osmar N.; Gonçalves, Sônia; Santos, Nuno C.; Franco, Octávio L.

    2017-02-01

    In recent years, the number of people suffering from cancer and multi-resistant infections has increased, such that both diseases are already seen as current and future major causes of death. Moreover, chronic infections are one of the main causes of cancer, due to the instability in the immune system that allows cancer cells to proliferate. Likewise, the physical debility associated with cancer or with anticancer therapy itself often paves the way for opportunistic infections. It is urgent to develop new therapeutic methods, with higher efficiency and lower side effects. Antimicrobial peptides (AMPs) are found in the innate immune system of a wide range of organisms. Identified as the most promising alternative to conventional molecules used nowadays against infections, some of them have been shown to have dual activity, both as antimicrobial and anticancer peptides (ACPs). Highly cationic and amphipathic, they have demonstrated efficacy against both conditions, with the number of nature-driven or synthetically designed peptides increasing year by year. With similar properties, AMPs that can also act as ACPs are viewed as future chemotherapeutic drugs, with the advantage of low propensity to resistance, which started this paradigm in the pharmaceutical market. These peptides have already been described as molecules presenting killing mechanisms at the membrane level, but also acting towards intracellular targets, which increases their success comparatively to specific one-target drugs. This review will approach the desirable characteristics of small peptides that demonstrated dual activity against microbial infections and cancer, as well as the peptides engaged in clinical trials.

  7. Neutron diffraction studies of viral fusion peptides

    NASA Astrophysics Data System (ADS)

    Bradshaw, Jeremy P.; J. M. Darkes, Malcolm; Katsaras, John; Epand, Richard M.

    2000-03-01

    Membrane fusion plays a vital role in a large and diverse number of essential biological processes. Despite this fact, the precise molecular events that occur during fusion are still not known. We are currently engaged on a study of membrane fusion as mediated by viral fusion peptides. These peptides are the N-terminal regions of certain viral envelope proteins that mediate the process of fusion between the viral envelope and the membranes of the host cell during the infection process. As part of this study, we have carried out neutron diffraction measurements at the ILL, BeNSC and Chalk River, on a range of viral fusion peptides. The peptides, from simian immunodeficiency virus (SIV), influenza A and feline leukaemia virus (FeLV), were incorporated into stacked phospholipid bilayers. Some of the peptides had been specifically deuterated at key amino acids. Lamellar diffraction data were collected and analysed to yield information on the peptide conformation, location and orientation relative to the bilayer.

  8. Self-Assembly of Tetraphenylalanine Peptides.

    PubMed

    Mayans, Enric; Ballano, Gema; Casanovas, Jordi; Díaz, Angélica; Pérez-Madrigal, Maria M; Estrany, Francesc; Puiggalí, Jordi; Cativiela, Carlos; Alemán, Carlos

    2015-11-16

    Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head-to-tail NH3(+)⋅⋅⋅(-)OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc) protected FFFF self-assembles into a variety of polymorphs: ultra-thin nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel β-sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. [Peptide phage display in biotechnology and biomedicine].

    PubMed

    Kuzmicheva, G A; Belyavskaya, V A

    2016-07-01

    To date peptide phage display is one of the most common combinatorial methods used for identifying specific peptide ligands. Phage display peptide libraries containing billions different clones successfully used for selection of ligands with high affinity and selectivity toward wide range of targets including individual proteins, bacteria, viruses, spores, different kind of cancer cells and variety of nonorganic targets (metals, alloys, semiconductors etc.) Success of using filamentous phage in phage display technologies relays on the robustness of phage particles and a possibility to genetically modify its DNA to construct new phage variants with novel properties. In this review we are discussing characteristics of the most known non-commercial peptide phage display libraries of different formats (landscape libraries in particular) and their successful applications in several fields of biotechnology and biomedicine: discovery of peptides with diagnostic values against different pathogens, discovery and using of peptides recognizing cancer cells, trends in using of phage display technologies in human interactome studies, application of phage display technologies in construction of novel nano materials.

  10. Biosynthetic engineering of nonribosomal peptide synthetases.

    PubMed

    Kries, Hajo

    2016-09-01

    From the evolutionary melting pot of natural product synthetase genes, microorganisms elicit antibiotics, communication tools, and iron scavengers. Chemical biologists manipulate these genes to recreate similarly diverse and potent biological activities not on evolutionary time scales but within months. Enzyme engineering has progressed considerably in recent years and offers new screening, modelling, and design tools for natural product designers. Here, recent advances in enzyme engineering and their application to nonribosomal peptide synthetases are reviewed. Among the nonribosomal peptides that have been subjected to biosynthetic engineering are the antibiotics daptomycin, calcium-dependent antibiotic, and gramicidin S. With these peptides, incorporation of unnatural building blocks and modulation of bioactivities via various structural modifications have been successfully demonstrated. Natural product engineering on the biosynthetic level is not a reliable method yet. However, progress in the understanding and manipulation of biosynthetic pathways may enable the routine production of optimized peptide drugs in the near future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  11. Biomathematical Description of Synthetic Peptide Libraries

    PubMed Central

    Trepel, Martin

    2015-01-01

    Libraries of randomised peptides displayed on phages or viral particles are essential tools in a wide spectrum of applications. However, there is only limited understanding of a library's fundamental dynamics and the influences of encoding schemes and sizes on their quality. Numeric properties of libraries, such as the expected number of different peptides and the library's coverage, have long been in use as measures of a library's quality. Here, we present a graphical framework of these measures together with a library's relative efficiency to help to describe libraries in enough detail for researchers to plan new experiments in a more informed manner. In particular, these values allow us to answer-in a probabilistic fashion-the question of whether a specific library does indeed contain one of the "best" possible peptides. The framework is implemented in a web-interface based on two packages, discreteRV and peptider, to the statistical software environment R. We further provide a user-friendly web-interface called PeLiCa (Peptide Library Calculator, http://www.pelica.org), allowing scientists to plan and analyse their peptide libraries. PMID:26042419

  12. Comprehensive computational design of ordered peptide macrocycles

    SciTech Connect

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple

    Mixed chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to-date, but there is currently no way to systematically search through the structural space spanned by such compounds for new drug candidates. Natural proteins do not provide a useful guide: peptide macrocycles lack regular secondary structures and hydrophobic cores and have different backbone torsional constraints. Hence the development of new peptide macrocycles has been approached by modifying natural products or using library selection methods; the former is limited by the small number of known structures, and the latter by the limited size and diversity accessible throughmore » library-based methods. To overcome these limitations, here we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L and D amino acids. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. We synthesize and characterize by NMR twelve 7-10 residue macrocycles, 9 of which have structures very close to the design models in solution. NMR structures of three 11-14 residue bicyclic designs are also very close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide based macrocycles unparalleled for other molecular systems, and vastly increase the available starting scaffolds for both rational drug design and library selection methods.« less

  13. Peptides as Therapeutic Agents for Dengue Virus

    PubMed Central

    Chew, Miaw-Fang; Poh, Keat-Seong; Poh, Chit-Laa

    2017-01-01

    Dengue is an important global threat caused by dengue virus (DENV) that records an estimated 390 million infections annually. Despite the availability of CYD-TDV as a commercial vaccine, its long-term efficacy against all four dengue virus serotypes remains unsatisfactory. There is therefore an urgent need for the development of antiviral drugs for the treatment of dengue. Peptide was once a neglected choice of medical treatment but it has lately regained interest from the pharmaceutical industry following pioneering advancements in technology. In this review, the design of peptide drugs, antiviral activities and mechanisms of peptides and peptidomimetics (modified peptides) action against dengue virus are discussed. The development of peptides as inhibitors for viral entry, replication and translation is also described, with a focus on the three main targets, namely, the host cell receptors, viral structural proteins and viral non-structural proteins. The antiviral peptides designed based on these approaches may lead to the discovery of novel anti-DENV therapeutics that can treat dengue patients. PMID:29200948

  14. Effects of opioid peptides on thermoregulation

    SciTech Connect

    Clark, W.G.

    1981-11-01

    In a given species, injected opioid peptides usually cause changes in temperature similar to those caused by nonpeptide opioids. The main effect in those species most studied, the cat, rat, and mouse, is an increase in the level about which body temperature is regulated; there is a coordinated change in the activity of thermoregulatory effectors such that hyperthermia is produced in both hot and cold environments. Larger doses may depress thermoregulation, thereby causing body temperature to decrease in the cold. Elicitation of different patterns of response over a range of environmental temperatures and studies with naloxone and naltrexone indicate thatmore » stimulation of a number of different receptors by both peptide and nonpeptide opioids can evoke thermoregulatory responses. ..beta..-Endorphin is readily antagonized by naloxone whereas methionine-enkephalin can act on naloxone-insensitive receptors. Moreover, synthetic peptide analogs do not necessarily evoke the same response as does the related endogenous peptide. The lack of effect of naloxone on body temperature of subjects housed at usual laboratory temperature or on pyrogen-induced increases in body temperature indicates that an action of endogenous peptides on naloxone-sensitive receptors plays little, if any, role in normal thermoregulation or in fever. However, there is some evidence that such an action may be involved in responses to restraint or ambient temperature-induced stress. Further evaluation of possible physiological roles of endogenous opioid peptides will be facilitated when specific antagonists at other types of opioid receptors become available.« less

  15. Sequential and competitive adsorption of peptides at pendant PEO layers.

    PubMed

    Wu, Xiangming; Ryder, Matthew P; McGuire, Joseph; Snider, Joshua L; Schilke, Karl F

    2015-06-01

    Earlier work provided direction for development of responsive drug delivery systems based on modulation of the structure, amphiphilicity, and surface density of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. In this work, we describe the sequential and competitive adsorption behavior of such peptides at pendant PEO layers. Three cationic peptides were used for this purpose: the arginine-rich, amphiphilic peptide WLBU2, a peptide chemically identical to WLBU2 but of scrambled sequence (S-WLBU2), and the non-amphiphilic peptide poly-L-arginine (PLR). Optical waveguide lightmode spectroscopy (OWLS) was used to quantify the rate and extent of peptide adsorption and elution at surfaces coated with PEO. UV spectroscopy and time-of-flight secondary ion mass spectrometry (TOF-SIMS) were used to quantify the extent of peptide exchange during the course of sequential and competitive adsorption. Circular dichroism (CD) was used to evaluate conformational changes after adsorption of peptide mixtures at PEO-coated silica nanoparticles. Results indicated that amphiphilic peptides are able to displace adsorbed, non-amphiphilic peptides in PEO layers, while non-amphiphilic peptides were not able to displace more amphiphilic peptides. In addition, peptides of greater amphiphilicity dominated the adsorption at the PEO layer from mixtures with less amphiphilic or non-amphiphilic peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Peptide library synthesis on spectrally encoded beads for multiplexed protein/peptide bioassays

    NASA Astrophysics Data System (ADS)

    Nguyen, Huy Q.; Brower, Kara; Harink, Björn; Baxter, Brian; Thorn, Kurt S.; Fordyce, Polly M.

    2017-02-01

    Protein-peptide interactions are essential for cellular responses. Despite their importance, these interactions remain largely uncharacterized due to experimental challenges associated with their measurement. Current techniques (e.g. surface plasmon resonance, fluorescence polarization, and isothermal calorimetry) either require large amounts of purified material or direct fluorescent labeling, making high-throughput measurements laborious and expensive. In this report, we present a new technology for measuring antibody-peptide interactions in vitro that leverages spectrally encoded beads for biological multiplexing. Specific peptide sequences are synthesized directly on encoded beads with a 1:1 relationship between peptide sequence and embedded code, thereby making it possible to track many peptide sequences throughout the course of an experiment within a single small volume. We demonstrate the potential of these bead-bound peptide libraries by: (1) creating a set of 46 peptides composed of 3 commonly used epitope tags (myc, FLAG, and HA) and single amino-acid scanning mutants; (2) incubating with a mixture of fluorescently-labeled antimyc, anti-FLAG, and anti-HA antibodies; and (3) imaging these bead-bound libraries to simultaneously identify the embedded spectral code (and thus the sequence of the associated peptide) and quantify the amount of each antibody bound. To our knowledge, these data demonstrate the first customized peptide library synthesized directly on spectrally encoded beads. While the implementation of the technology provided here is a high-affinity antibody/protein interaction with a small code space, we believe this platform can be broadly applicable to any range of peptide screening applications, with the capability to multiplex into libraries of hundreds to thousands of peptides in a single assay.

  17. Virtual screening using combinatorial cyclic peptide libraries reveals protein interfaces readily targetable by cyclic peptides.

    PubMed

    Duffy, Fergal J; O'Donovan, Darragh; Devocelle, Marc; Moran, Niamh; O'Connell, David J; Shields, Denis C

    2015-03-23

    Protein-protein and protein-peptide interactions are responsible for the vast majority of biological functions in vivo, but targeting these interactions with small molecules has historically been difficult. What is required are efficient combined computational and experimental screening methods to choose among a number of potential protein interfaces worthy of targeting lead macrocyclic compounds for further investigation. To achieve this, we have generated combinatorial 3D virtual libraries of short disulfide-bonded peptides and compared them to pharmacophore models of important protein-protein and protein-peptide structures, including short linear motifs (SLiMs), protein-binding peptides, and turn structures at protein-protein interfaces, built from 3D models available in the Protein Data Bank. We prepared a total of 372 reference pharmacophores, which were matched against 108,659 multiconformer cyclic peptides. After normalization to exclude nonspecific cyclic peptides, the top hits notably are enriched for mimetics of turn structures, including a turn at the interaction surface of human α thrombin, and also feature several protein-binding peptides. The top cyclic peptide hits also cover the critical "hot spot" interaction sites predicted from the interaction crystal structure. We have validated our method by testing cyclic peptides predicted to inhibit thrombin, a key protein in the blood coagulation pathway of important therapeutic interest, identifying a cyclic peptide inhibitor with lead-like activity. We conclude that protein interfaces most readily targetable by cyclic peptides and related macrocyclic drugs may be identified computationally among a set of candidate interfaces, accelerating the choice of interfaces against which lead compounds may be screened.

  18. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    PubMed

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

    Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Bioactive dietary peptides and amino acids in inflammatory bowel disease.

    PubMed

    Zhang, Hua; Hu, Chien-An A; Kovacs-Nolan, Jennifer; Mine, Yoshinori

    2015-10-01

    Inflammatory bowel disease (IBD), most commonly ulcerative colitis (UC) and Crohn's disease (CD), is a chronic inflammation of the gastrointestinal tract. Patients affected with IBD experience symptoms including abdominal pain, persistent diarrhea, rectal bleeding, and weight loss. There is no cure for IBD; thus treatments typically focus on preventing complications, inducing and maintaining remission, and improving quality of life. During IBD, dysregulation of the intestinal immune system leads to increased production of pro-inflammatory cytokines, such as TNF-α and IL-6, and recruitment of activated immune cells to the intestine, causing tissue damage and perpetuating the inflammatory response. Recent biological therapies targeting specific inflammatory cytokines or pathways, in particular TNF-α, have shown promise, but not all patients respond to treatment, and some individuals become intolerant to treatment over time. Dietary peptides and amino acids (AAs) have been shown to modulate intestinal immune functions and influence inflammatory responses, and may be useful as alternative or ancillary treatments in IBD. This review focuses on dietary interventions for IBD treatment, in particular the role of dietary peptides and AAs in reducing inflammation, oxidative stress, and apoptosis in the gut, as well as recent advances in the cellular mechanisms responsible for their anti-inflammatory activity.

  20. Peptide Epimerization Machineries Found in Microorganisms.

    PubMed

    Ogasawara, Yasushi; Dairi, Tohru

    2018-01-01

    D-Amino acid residues have been identified in peptides from a variety of eukaryotes and prokaryotes. In microorganisms, UDP- N -acetylmuramic acid pentapeptide (UDP-MurNAc-L-Ala-D-Glu-meso-diaminopimelate-D-Ala-D-Ala), a unit of peptidoglycan, is a representative. During its biosynthesis, D-Ala and D-Glu are generally supplied by racemases from the corresponding isomers. However, we recently identified a unique unidirectional L-Glu epimerase catalyzing the epimerization of the terminal L-Glu of UDP-MurNAc-L-Ala-L-Glu. Several such enzymes, introducing D-amino acid resides into peptides via epimerization, have been reported to date. This includes a L-Ala-D/L-Glu epimerase, which is possibly used during peptidoglycan degradation. In bacterial primary metabolisms, to the best of our knowledge, these two machineries are the only examples of peptide epimerization. However, a variety of peptides containing D-amino acid residues have been isolated from microorganisms as secondary metabolites. Their biosynthetic mechanisms have been studied and three different peptide epimerization machineries have been reported. The first is non-ribosomal peptide synthetase (NRPS). Excellent studies with dissected modules of gramicidin synthetase and tyrocidine synthetase revealed the reactions of the epimerization domains embedded in the enzymes. The obtained information is still utilized to predict epimerization domains in uncharacterized NRPSs. The second includes the biosynthetic enzymes of lantibiotics, which are ribosome-dependently supplied peptide antibiotics containing polycyclic thioether amino acids (lanthionines). A mechanism for the formation of the D-Ala moiety in lanthionine by two enzymes, dehydratases catalyzing the conversion of L-Ser into dehydroalanine and enzymes catalyzing nucleophilic attack of the thiol of cysteine into dehydroalanine, was clarified. Similarly, the formation of a D-Ala residue by reduction of the dehydroalanine residue was also reported. The last

  1. Growth hormone-releasing peptides.

    PubMed

    Ghigo, E; Arvat, E; Muccioli, G; Camanni, F

    1997-05-01

    Growth hormone-releasing peptides (GHRPs) are synthetic, non-natural peptides endowed with potent stimulatory effects on somatotrope secretion in animals and humans. They have no structural homology with GHRH and act via specific receptors present either at the pituitary or the hypothalamic level both in animals and in humans. The GHRP receptor has recently been cloned and, interestingly, it does not show sequence homology with other G-protein-coupled receptors known so far. This evidence strongly suggests the existence of a natural GHRP-like ligand which, however, has not yet been found. The mechanisms underlying the GHRP effect are still unclear. At present, several data favor the hypothesis that GHRPs could act by counteracting somatostatinergic activity both at the pituitary and the hypothalamic level and/or, at least partially, via a GHRH-mediated mechanism. However, the possibility that GHRPs act via an unknown hypothalamic factor (U factor) is still open. GHRP-6 was the first hexapeptide to be extensively studied in humans. More recently, a heptapeptide, GHRP-1, and two other hexapeptides, GHRP-2 and Hexarelin, have been synthesized and are now available for human studies. Moreover, non-peptidyl GHRP mimetics have been developed which act via GHRP receptors and their effects have been clearly demonstrated in animals and in humans in vivo. Among non-peptidyl GHRPs, MK-0677 seems the most interesting molecule. The GH-releasing activity of GHRPs is marked and dose-related after intravenous, subcutaneous, intranasal and even oral administration. The effect of GHRPs is reproducible and undergoes partial desensitization, more during continuous infusion, less during intermittent administration: in fact, prolonged administration of GHRPs increases IGF-1 levels both in animals and in humans. The GH-releasing effect of GHRPs does not depend on sex but undergoes age-related variations. It increases from birth to puberty, persists at a similar level in adulthood and

  2. Interleukin-2 concentration in hypothalamic structures of rats receiving peptides during mild stress.

    PubMed

    Barabanova, S V; Artyukhina, Z E; Kazakova, T B; Khavinson, V Kh; Malinin, V V; Korneva, E A

    2006-04-01

    The number of hypothalamic IL-2-containing cells changed in rats receiving Vilon and Epithalon during mild stress (handling). The number of IL-2-positive cells in hypothalamic structures decreased 24 h after intramuscular injection of Epithalon and 2 h after intranasal administration of the test peptides. Adaptation of animals to experimental conditions prevented the decrease in the number of IL-2-positive cells in the supraoptic nucleus after intranasal administration of Epithalon.

  3. Peptide mediators of cholesterol efflux

    DOEpatents

    Bielicki, John K.; Johansson, Jan

    2013-04-09

    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  4. Human antimicrobial peptides and cancer.

    PubMed

    Jin, Ge; Weinberg, Aaron

    2018-05-30

    Antimicrobial peptides (AMPs) have long been a topic of interest for entomologists, biologists, immunologists and clinicians because of these agents' intriguing origins in insects, their ubiquitous expression in many life forms, their capacity to kill a wide range of bacteria, fungi and viruses, their role in innate immunity as microbicidal and immunoregulatory agents that orchestrate cross-talk with the adaptive immune system, and, most recently, their association with cancer. We and others have theorized that surveillance through epithelial cell-derived AMPs functions to keep the natural flora of microorganisms in a steady state in different niches such as the skin, the intestines, and the mouth. More recently, findings related to specific activation pathways of some of these AMPs have led investigators to associate them with pro-tumoral activity; i.e., contributing to a tumorigenic microenvironment. This area is still in its infancy as there are intriguing yet contradictory findings demonstrating that while some AMPs have anti-tumoral activity and are under-expressed in solid tumors, others are overexpressed and pro-tumorigenic. This review will introduce a new paradigm in cancer biology as it relates to AMP activity in neoplasia to address the following questions: Is there evidence that AMPs contribute to tumor promoting microenvironments? Can an anti-AMP strategy be of use in cancer therapy? Do AMPs, expressed in and released from tumors, contribute to compositional shifting of bacteria in cancerous lesions? Can specific AMP expression characteristics be used one day as early warning signs for solid tumors? Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings.

    PubMed

    Ayres, Cory M; Corcelli, Steven A; Baker, Brian M

    2017-01-01

    Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic "energy landscapes" of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

  6. Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings

    PubMed Central

    Ayres, Cory M.; Corcelli, Steven A.; Baker, Brian M.

    2017-01-01

    Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic “energy landscapes” of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology. PMID:28824655

  7. Myoinhibiting peptides are the ancestral ligands of the promiscuous Drosophila sex peptide receptor

    USDA-ARS?s Scientific Manuscript database

    Male insects change behaviors of female partners by co-transferring accessory gland proteins (Acps) like sex peptide (SP), with their sperm. The Drosophila sex peptide receptor (SPR) is a G protein-coupled receptor expressed in the female’s nervous system and genital tract. While most Acps show a fa...

  8. Antigenic properties of HCMV peptides displayed by filamentous bacteriophages vs. synthetic peptides.

    PubMed

    Ulivieri, Cristina; Citro, Alessandra; Ivaldi, Federico; Mascolo, Dina; Ghittoni, Raffaella; Fanigliulo, Daniela; Manca, Fabrizio; Baldari, Cosima Tatiana; Li Pira, Giuseppina; Del Pozzo, Giovanna

    2008-08-15

    Several efforts have been invested in the identification of CTL and Th epitopes, as well as in the characterization of their immunodominance and MHC restriction, for the generation of a peptide-based HCMV vaccine. Small synthetic peptides are, however, poor antigens and carrier proteins are important for improving the efficacy of synthetic peptide vaccines. Recombinant bacteriophages appear as promising tools in the design of subunit vaccines. To investigate the antigenicity of peptides carried by recombinant bacteriophages we displayed different HCMV MHCII restricted peptides on the capsid of filamentous bacteriophage (fd) and found that hybrid bacteriophages are processed by human APC and activate HCMV-specific CD4 T-cells. Furthermore we constructed a reporter T-cell hybridoma expressing a chimeric TCR comprising murine alphabeta constant regions and human variable regions specific for the HLA-A2 restricted immunodominant NLV peptide of HCMV. Using the filamentous bacteriophage as an epitope carrier, we detected a more robust and long lasting response of the reporter T-cell hybridoma compared to peptide stimulation. Our results show a general enhancement of T-cell responses when antigenic peptides are carried by phages.

  9. A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone.

    PubMed

    Pruitt, Rory N; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R; Ronald, Pamela C

    2017-07-01

    The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides. Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides. Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence. These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. © 2017 UT-Battelle LLC. New Phytologist © 2017 New Phytologist Trust.

  10. A microbially derived tyrosine-sulfated peptide mimics a plant peptide hormone

    PubMed Central

    Pruitt, Rory N.; Joe, Anna; Zhang, Weiguo; Feng, Wei; Stewart, Valley; Schwessinger, Benjamin; Dinneny, José R.; Ronald, Pamela C.

    2018-01-01

    Summary The biotrophic pathogen Xanthomonas oryzae pv. oryzae (Xoo) produces a sulfated peptide named RaxX, which shares similarity to peptides in the PSY (plant peptide containing sulfated tyrosine) family. We hypothesize that RaxX mimics the growth-stimulating activity of PSY peptides.Root length was measured in Arabidopsis and rice treated with synthetic RaxX peptides. We also used comparative genomic analyses and reactive oxygen species burst assays to evaluate the activity of RaxX and PSY peptides.Here we found that a synthetic sulfated RaxX derivative comprising 13 residues (RaxX13-sY), highly conserved between RaxX and PSY, induces root growth in Arabidopsis and rice in a manner similar to that triggered by PSY. We identified residues that are required for activation of immunity mediated by the rice XA21 receptor but that are not essential for root growth induced by PSY. Finally, we showed that a Xanthomonas strain lacking raxX is impaired in virulence.These findings suggest that RaxX serves as a molecular mimic of PSY peptides to facilitate Xoo infection and that XA21 has evolved the ability to recognize and respond specifically to the microbial form of the peptide. PMID:28556915

  11. Manual Solid-Phase Peptide Synthesis of Metallocene-Peptide Bioconjugates

    ERIC Educational Resources Information Center

    Kirin, Srecko I.; Noor, Fozia; Metzler-Nolte, Nils; Mier, Walter

    2007-01-01

    A simple and relatively inexpensive procedure for preparing a biologically active peptide using solid phase peptide synthesis (SPPS) is described. Fourth-year undergraduate students have gained firsthand experience from the solid-phase synthesis techniques and they have become familiar with modern analytical techniques based on the particular…

  12. A novel antimicrobial peptide against dental-caries-associated bacteria.

    PubMed

    Chen, Long; Jia, Lili; Zhang, Qiang; Zhou, Xirui; Liu, Zhuqing; Li, Bingjie; Zhu, Zhentai; Wang, Fenwei; Yu, Changyuan; Zhang, Qian; Chen, Feng; Luo, Shi-Zhong

    2017-10-01

    Dental caries, a highly prevalent oral disease, is primarily caused by pathogenic bacteria infection, and most of them are anaerobic. Herein, we investigated the activity of a designed antimicrobial peptide ZXR-2, and found it showed broad-spectrum activity against a variety of Gram-positive and Gram-negative oral bacteria, particularly the caries-related taxa Streptococcus mutans. Time-course killing assays indicated that ZXR-2 killed most bacterial cells within 5 min at 4 × MIC. The mechanism of ZXR-2 involved disruption of cell membranes, as observed by scanning electron microscopy. Moreover, ZXR-2 inhibited the formation of S. mutans biofilm, but showed limited hemolytic effect. Based on its potent antimicrobial activity, rapid killing, and inhibition of S. mutans biofilm formation, ZXR-2 represents a potential therapeutic for the prevention and treatment of dental caries. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Porphyrin Cyclodextrin Conjugates Modulate Amyloid Beta Peptide Aggregation and Cytotoxicity.

    PubMed

    Oliveri, Valentina; Zimbone, Stefania; Giuffrida, Maria Laura; Bellia, Francesco; Tomasello, Marianna Flora; Vecchio, Graziella

    2018-04-25

    Although fibrillar amyloid beta peptide (Aβ) aggregates are one of the major hallmarks of Alzheimer's disease, increasing evidence suggests that soluble Aβ oligomers are the primary toxic species. Targeting the oligomeric species could represent an effective strategy to interfere with Aβ toxicity. In this work, the biological properties of 5[4-(6-O-β-cyclodextrin)-phenyl],10,15,20-tri(4-hydroxyphenyl)-porphyrin and its zinc complex were tested, as new molecules that interact with Aβ and effectively prevent its cytotoxicity. We found that these systems can cross the cell membrane to deliver Aβ intracellularly and promote its clearance. Our results provide evidence for the use of cyclodextrin-porphyrin derivatives as a promising strategy to target amyloid aggregation. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Cationic Antimicrobial Peptide Resistance Mechanisms of Streptococcal Pathogens

    PubMed Central

    LaRock, Christopher N.; Nizet, Victor

    2015-01-01

    Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. PMID:25701232

  15. Bombesin, somatostatin, and related peptides: actions on thermoregulation

    SciTech Connect

    Brown, M.R.

    1981-11-01

    Bombesin acts within the anterior hypothalamic preoptic area to interfere with thermoregulation in the rat. The body temperature (T/sub b/) of animals receiving bombesin varies in parallel with ambient temperature (T/sub a/). Bombesin-induced reduction of T/sub b/ in animals at low T/sub a/ is associated with a marked reduction of oxygen consumption (Vo/sub 2/). Some somatostatin-related peptides, e.g., desAA/sup 1,2,4,5,12,13/ (D-Trp/sup 8/)-somatostatin (ODT8-SS), act within the brain to prevent bombesin-induced reduction of Vo/sub 2/ and T/sub b/. ODT8-SS also produces hyperthermia not associated with an increase in Vo/sub 2/.

  16. Acetone-Linked Peptides: A Convergent Approach for Peptide Macrocyclization and Labeling.

    PubMed

    Assem, Naila; Ferreira, David J; Wolan, Dennis W; Dawson, Philip E

    2015-07-20

    Macrocyclization is a broadly applied approach for overcoming the intrinsically disordered nature of linear peptides. Herein, it is shown that dichloroacetone (DCA) enhances helical secondary structures when introduced between peptide nucleophiles, such as thiols, to yield an acetone-linked bridge (ACE). Aside from stabilizing helical structures, the ketone moiety embedded in the linker can be modified with diverse molecular tags by oxime ligation. Insights into the structure of the tether were obtained through co-crystallization of a constrained S-peptide in complex with RNAse S. The scope of the acetone-linked peptides was further explored through the generation of N-terminus to side chain macrocycles and a new approach for generating fused macrocycles (bicycles). Together, these studies suggest that acetone linking is generally applicable to peptide macrocycles with a specific utility in the synthesis of stabilized helices that incorporate functional tags. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Synthesis, molecular docking and anticancer studies of peptides and iso-peptides.

    PubMed

    Jabeen, Farukh; Panda, Siva S; Kondratyuk, Tamara P; Park, Eun-Jung; Pezzuto, John M; Ihsan-ul-Haq; Hall, C Dennis; Katritzky, Alan R

    2015-08-01

    Chiral peptides and iso-peptides were synthesized in excellent yield by using benzotriazole mediated solution phase synthesis. Benzotriazole acted both as activating and leaving group, eliminating frequent use of protection and subsequent deprotection. The procedure was based on the hypothesis that epimerization should be suppressed in solution due to a faster coupling rate than SPPS. All the synthesized peptides complied with Lipinski's Ro5 except for the rotatable bonds. Inhibition of cell proliferation of cancer cell lines is one of the most commonly used methods to study the effectiveness of any anticancer agents. Synthesized peptides and iso-peptides were tested against three cancer cell lines (MCF-7, MDA-MB 231) to determine their anti-proliferative potential. NFkB was also determined. Molecular docking studies were also carried out to complement the experimental results. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Simulation-based Discovery of Cyclic Peptide Nanotubes

    NASA Astrophysics Data System (ADS)

    Ruiz Pestana, Luis A.

    Today, there is a growing need for environmentally friendly synthetic membranes with selective transport capabilities to address some of society's most pressing issues, such as carbon dioxide pollution, or access to clean water. While conventional membranes cannot stand up to the challenge, thin nanocomposite membranes, where vertically aligned subnanometer pores (e.g. nanotubes) are embedded in a thin polymeric film, promise to overcome some of the current limitations, namely, achieving a monodisperse distribution of subnanometer size pores, vertical pore alignment across the membrane thickness, and tunability of the pore surface chemistry. Self-assembled cyclic peptide nanotubes (CPNs), are particularly promising as selective nanopores because the pore size can be controlled at the subnanometer level, exhibit high chemical design flexibility, and display remarkable mechanical stability. In addition, when conjugated with polymer chains, the cyclic peptides can co-assemble in block copolymer domains to form nanoporous thin films. CPNs are thus well positioned to tackle persistent challenges in molecular separation applications. However, our poor understanding of the physics underlying their remarkable properties prevents the rational design and implementation of CPNs in technologically relevant membranes. In this dissertation, we use a simulation-based approach, in particular molecular dynamics (MD) simulations, to investigate the critical knowledge gaps hindering the implementation of CPNs. Computational mechanical tests show that, despite the weak nature of the stabilizing hydrogen bonds and the small cross section, CPNs display a Young's modulus of approximately 20 GPa and a maximum strength of around 1 GPa, placing them among the strongest proteinaceous materials known. Simulations of the self-assembly process reveal that CPNs grow by self-similar coarsening, contrary to other low-dimensional peptide systems, such as amyloids, that are believed to grow through

  19. Slc15a1 is involved in the transport of synthetic F5-peptide into the seminiferous epithelium in adult rat testes

    PubMed Central

    Su, Linlin; Zhang, Yufei; Cheng, Yan C.; Lee, Will M.; Ye, Keping; Hu, Dahai

    2015-01-01

    Spermiation and BTB restructuring, two critical cellular events that occur across seminiferous epithelium in mammalian testis during spermatogenesis, are tightly coordinated by biologically active peptides released from laminin chains. Our earlier study reported that F5-peptide, synthesized based on a stretch of 50 amino acids within laminin-γ3 domain IV, could reversibly induce the impairment of spermatogenesis, disruption of BTB integrity, and germ cell loss, and thus is a promising male contraceptive. However, how F5-peptide when administered intratesticularly enters seminiferous tubules and exerts effects beyond BTB is currently unknown. Here we demonstrated that Slc15a1, a peptide transporter also known as Pept1, was predominantly present in peritubular myoid cells, interstitial Leydig cells, vascular endothelial cells and germ cells, while absent in Sertoli cells or BTB site. The steady-state protein level of Slc15a1 in adult rat testis was not affected by F5-peptide treatment. Knockdown of Slc15a1 by in vivo RNAi in rat testis was shown to prevent F5-peptide induced disruptive effects on spermatogenesis. This study suggests that Slc15a1 is involved in the transport of synthetic F5-peptide into seminiferous epithelium, and thus Slc15a1 is a novel target in testis that could be genetically modified to improve the bioavailability of F5-peptide as a prospective male contraceptive. PMID:26537751

  20. Slc15a1 is involved in the transport of synthetic F5-peptide into the seminiferous epithelium in adult rat testes.

    PubMed

    Su, Linlin; Zhang, Yufei; Cheng, Yan C; Lee, Will M; Ye, Keping; Hu, Dahai

    2015-11-05

    Spermiation and BTB restructuring, two critical cellular events that occur across seminiferous epithelium in mammalian testis during spermatogenesis, are tightly coordinated by biologically active peptides released from laminin chains. Our earlier study reported that F5-peptide, synthesized based on a stretch of 50 amino acids within laminin-γ3 domain IV, could reversibly induce the impairment of spermatogenesis, disruption of BTB integrity, and germ cell loss, and thus is a promising male contraceptive. However, how F5-peptide when administered intratesticularly enters seminiferous tubules and exerts effects beyond BTB is currently unknown. Here we demonstrated that Slc15a1, a peptide transporter also known as Pept1, was predominantly present in peritubular myoid cells, interstitial Leydig cells, vascular endothelial cells and germ cells, while absent in Sertoli cells or BTB site. The steady-state protein level of Slc15a1 in adult rat testis was not affected by F5-peptide treatment. Knockdown of Slc15a1 by in vivo RNAi in rat testis was shown to prevent F5-peptide induced disruptive effects on spermatogenesis. This study suggests that Slc15a1 is involved in the transport of synthetic F5-peptide into seminiferous epithelium, and thus Slc15a1 is a novel target in testis that could be genetically modified to improve the bioavailability of F5-peptide as a prospective male contraceptive.

  1. Inhibition of the aggregation of lactoferrin and (-)-epigallocatechin gallate in the presence of polyphenols, oligosaccharides, and collagen peptide.

    PubMed

    Yang, Wei; Liu, Fuguo; Xu, Chenqi; Sun, Cuixia; Yuan, Fang; Gao, Yanxiang

    2015-05-27

    The aggregation of lactoferrin and (-)-epigallocatechin gallate (EGCG) was inhibited by polyphenols, oligosaccharides, and collagen peptide in this study. Polyphenols, oligosaccharides, or collagen peptide can effectively prevent the formation of lactoferrin-EGCG aggregates, respectively. The addition sequence of lactoferrin, polyphenols (oligosaccharides or collagen peptide) and EGCG can affect the turbidity and particle size of the ternary complexes in the buffer solution; however, it hardly affected the ζ-potential and fluorescence characteristics. With either positive or negative charge, polyphenols and collagen peptide disrupted the formation of lactoferrin-EGCG aggregate mainly through the mechanism of its competition with EGCG molecules which surrounded the lactoferrin molecule surface with weaker binding affinities, forming polyphenols or a collagen peptide-lactoferrin-EGCG ternary complex; for neutral oligosaccharides, the ternary complex was generated mainly through steric effects, accompanied by a change in the lactoferrin secondary structure induced by gallic acid, chlorogenic acid, and xylo-oligosaccharide. Polyphenols, oligosaccharides, or collagen peptide restraining the formation of lactoferrin-EGCG aggregate could be applied in the design of clear products in the food, pharmaceutical, and cosmetic industries.

  2. pH responsive micelle self-assembled from a new amphiphilic peptide as anti-tumor drug carrier.

    PubMed

    Liang, Ju; Wu, Wen-Lan; Xu, Xiao-Ding; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2014-02-01

    An acid-responsive amphiphilic peptide that contains KKGRGDS sequence in hydrophilic head and VVVVVV sequence in hydrophobic tail was designed and prepared. In neutral or basic medium, this amphiphilic peptide can self-assemble into micelles through hydrogen bonding and hydrophobic interactions. If changing the solution pH to an acidic environment, the electrostatic repulsion interaction among the ionized lysine (K) residues will prevent the self-assembly of the amphiphilic peptide, leading to the dissociation of micelles. The anti-tumor drug of doxorubicin (DOX) was chosen and loaded into the self-assembled micelles of the amphiphilic peptide to investigate the influence of external pH change on the drug release behavior. As expected, the micelles show a sustained DOX release in neutral medium (pH 7.0) but fast release behavior in acidic medium (pH 5.0). When incubating these DOX-loaded micelles with HeLa and COS7 cells, due to the over-expression of integrins on cancer cells, the micelles can efficiently use the tumor-targeting function of RGD sequence to deliver the drug into HeLa cells. Combined with the low cytotoxicity of the amphiphilic peptide against both HeLa and COS7 cells, the amphiphilic peptide reported in this work may be promising in clinical application for targeted drug delivery. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. An immunoproteomic approach revealing peptides from Sporothrix brasiliensis that induce a cellular immune response in subcutaneous sporotrichosis.

    PubMed

    de Almeida, José Roberto Fogaça; Jannuzzi, Grasielle Pereira; Kaihami, Gilberto Hideo; Breda, Leandro Carvalho Dantas; Ferreira, Karen Spadari; de Almeida, Sandro Rogério

    2018-03-08

    Sporothrix brasiliensis is the most virulent fungus of the Sporothrix complex and is the main species recovered in the sporotrichosis zoonotic hyperendemic area in Rio de Janeiro. A vaccine against S. brasiliensis could improve the current sporotrichosis situation. Here, we show 3 peptides from S. brasiliensis immunogenic proteins that have a higher likelihood for engaging MHC-class II molecules. We investigated the efficiency of the peptides as vaccines for preventing subcutaneous sporotrichosis. In this study, we observed a decrease in lesion diameters in peptide-immunized mice, showing that the peptides could induce a protective immune response against subcutaneous sporotrichosis. ZR8 peptide is from the GP70 protein, the main antigen of the Sporothrix complex, and was the best potential vaccine candidate by increasing CD4 + T cells and higher levels of IFN-γ, IL-17A and IL-1β characterizing a strong cellular immune response. This immune environment induced a higher number of neutrophils in lesions that are associated with fungus clearance. These results indicated that the ZR8 peptide induces a protective immune response against subcutaneous sporotrichosis and is a vaccine candidate against S. brasiliensis infection.

  4. pH-dependent and pH-independent self-assembling behavior of surfactant-like peptides

    NASA Astrophysics Data System (ADS)

    Gurevich, Leonid; Fojan, Peter

    2012-02-01

    Self-assembly of amphiphilic peptides designed during the last years by several research groups leads to a large variety of 3D-structures that already found applications in stabilization of large protein complexes, cell culturing systems etc. In this report, we present synthesis and characterization of two novel families of amphiphilic peptides KAn and KAnW (n=6,5,4) that exhibits clear charge separation controllable by pH of the environment. As the pH changes from acidic to basic, the charge on the ends of the peptide molecule varies eventually leading to reorganization of KAn micelles and even micellar inversion. On contrary, the bulky geometry of the tryptophan residue in KAnW limits the variation of the surfactant parameter and hence largely prevents assembly into spherical or cylindrical micelles while favouring flatter geometries. The studied short peptide families demonstrate formation of ordered aggregates with well-defined secondary structure from short unstructured peptides and provide a simple system where factors responsible for self-assembly can be singled out and studied one by one. The ability to control the shape and structure of peptide aggregates can provide basis for novel designer pH sensitive materials including drug delivery and controlled release systems.

  5. Identification and characterization of a salivary-pellicle-binding peptide by phage display.

    PubMed

    Cukkemane, Nivedita; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Veerman, Enno C I

    2014-05-01

    Dental biofilms are associated with oral diseases, making their control necessary. One way to control them is to prevent initial bacterial adherence to the salivary pellicle and thereby eventually decrease binding of late colonizing potential pathogens. The goal of this study was to generate a salivary-pellicle-binding peptide (SPBP) with antifouling activity towards primary colonizing bacteria. In order to achieve this goal we aimed to: (i) identify novel SPBPs by phage display; (ii) characterize the binding and antifouling properties of the selected SPBPs. A library of 2×10(9) phages displaying a random sequence of 12-mer peptides was used to identify peptides that bound selectively to the in vitro salivary pellicle. Three rounds of panning resulted in the selection of 10 pellicle-binding phages, each displaying a novel peptide sequence. The peptides were synthesized and their binding to the in vitro salivary pellicle was characterized in the presence and absence of calcium ions and Tween-20. The antifouling property of hydroxyapatite (HA) and saliva-coated HA discs treated with and without SPBPs were evaluated against Streptococcus gordonii. Ten unique SPBPs were identified using the phage display. One of these peptides, SPBP 10 (NSAAVRAYSPPS), exhibited significant binding to the in vitro salivary pellicle which was neither influenced by calcium ions, nor affected by up to 0.5% Tween-20. Its antifouling property against S. gordonii was significantly higher on the treated surfaces than on untreated surfaces. Use of the phage display library enabled us to find a specific SPBP with antifouling property towards S. gordonii. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Self-Assembly Drug Delivery System Based on Programmable Dendritic Peptide Applied in Multidrug Resistance Tumor Therapy.

    PubMed

    Chen, Si; Fan, Jin-Xuan; Qiu, Wen-Xiu; Liu, Li-Han; Cheng, Han; Liu, Fan; Yan, Guo-Ping; Zhang, Xian-Zheng

    2017-11-01

    In recent decades, diverse drug delivery systems (DDS) constructed by self-assembly of dendritic peptides have shown advantages and improvable potential for cancer treatment. Here, an arginine-enriched dendritic amphiphilic chimeric peptide CRRK(RRCG(Fmoc)) 2 containing multiple thiol groups is programmed to form drug-loaded nano-micelles by self-assembly. With a rational design, the branched hydrophobic groups (Fmoc) of the peptides provide a strong hydrophobic force to prevent the drug from premature release, and the reduction-sensitive disulfide linkages formed between contiguous peptides can control drug release under reducing stimulation. As expected, specific to multidrug resistance (MDR) tumor cells, the arginine-enriched peptide/drug (PD) nano-micelles show accurate nuclear localization ability to prevent the drug being pumped by P-glycoprotein (P-gp) in vitro, as well as exhibiting satisfactory efficacy for MDR tumor treatment in vivo. This design successfully realizes stimuli-responsive drug release aimed at MDR tumor cells via an ingenious sequence arrangement. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Allergy prevention.

    PubMed

    Muche-Borowski, Cathleen; Kopp, Matthias; Reese, Imke; Sitter, Helmut; Werfel, Thomas; Schäfer, Torsten

    2009-09-01

    Evidence-based primary prevention of allergic conditions is important in view of their increasing prevalence in Western industrialized countries. The Cochrane and Medline databases were searched for relevant scientific publications that appeared from February 2003 to May 2008. Articles in the reference lists of recent reviews were also considered, and experts were directly asked for their opinions. The retrieved publications were screened for relevance by evaluation of the title and abstract, and then by evaluation of the entire text. Each study chosen for inclusion was assigned an evidence grade as well as a grade for study quality relating to its potential for bias (low or high). The revised recommendations were then formally accepted by a consensus of representatives of medical specialist societies and other organizations, including a patient self-help group. The search initially yielded 4556 results out of which 217 articles (4 Cochrane reviews, 14 meta-analyses, 19 randomized clinical trials, 135 cohort studies, and 45 case-control studies) were chosen for inclusion and critical appraisal. No major changes ensued in the existing recommendations to avoid exposure to tobacco smoke, breast-feed for 4 months (or use hypoallergenic formulas), avoid a mould-promoting indoor climate, avoid exposure to furry pets (particularly cats), and vaccinate according to the current recommendations of the Standing Committee on Vaccination of the Robert Koch Institute (Ständige Impfkommission, STIKO). Neither the delayed introduction of solid food nor the avoidance of potent dietary allergens is recommended as a means of primary prevention. New recommendations were issued regarding fish consumption (by the mother while breastfeeding and nursing, and by the infant as solid food), avoidance of overweight, and reduction of exposure to air pollutants. This updated guideline serves as an aid in giving patients current, evidence-based recommendations for allergy prevention.

  8. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    SciTech Connect

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results showmore » empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.« less

  9. Predicting intensity ranks of peptide fragment ions.

    PubMed

    Frank, Ari M

    2009-05-01

    Accurate modeling of peptide fragmentation is necessary for the development of robust scoring functions for peptide-spectrum matches, which are the cornerstone of MS/MS-based identification algorithms. Unfortunately, peptide fragmentation is a complex process that can involve several competing chemical pathways, which makes it difficult to develop generative probabilistic models that describe it accurately. However, the vast amounts of MS/MS data being generated now make it possible to use data-driven machine learning methods to develop discriminative ranking-based models that predict the intensity ranks of a peptide's fragment ions. We use simple sequence-based features that get combined by a boosting algorithm into models that make peak rank predictions with high accuracy. In an accompanying manuscript, we demonstrate how these prediction models are used to significantly improve the performance of peptide identification algorithms. The models can also be useful in the design of optimal multiple reaction monitoring (MRM) transitions, in cases where there is insufficient experimental data to guide the peak selection process. The prediction algorithm can also be run independently through PepNovo+, which is available for download from http://bix.ucsd.edu/Software/PepNovo.html.

  10. Predicting Intensity Ranks of Peptide Fragment Ions

    PubMed Central

    Frank, Ari M.

    2009-01-01

    Accurate modeling of peptide fragmentation is necessary for the development of robust scoring functions for peptide-spectrum matches, which are the cornerstone of MS/MS-based identification algorithms. Unfortunately, peptide fragmentation is a complex process that can involve several competing chemical pathways, which makes it difficult to develop generative probabilistic models that describe it accurately. However, the vast amounts of MS/MS data being generated now make it possible to use data-driven machine learning methods to develop discriminative ranking-based models that predict the intensity ranks of a peptide's fragment ions. We use simple sequence-based features that get combined by a boosting algorithm in to models that make peak rank predictions with high accuracy. In an accompanying manuscript, we demonstrate how these prediction models are used to significantly improve the performance of peptide identification algorithms. The models can also be useful in the design of optimal MRM transitions, in cases where there is insufficient experimental data to guide the peak selection process. The prediction algorithm can also be run independently through PepNovo+, which is available for download from http://bix.ucsd.edu/Software/PepNovo.html. PMID:19256476

  11. Peptide self-assembly: thermodynamics and kinetics.

    PubMed

    Wang, Juan; Liu, Kai; Xing, Ruirui; Yan, Xuehai

    2016-10-21

    Self-assembling systems play a significant role in physiological functions and have therefore attracted tremendous attention due to their great potential for applications in energy, biomedicine and nanotechnology. Peptides, consisting of amino acids, are among the most popular building blocks and programmable molecular motifs. Nanostructures and materials assembled using peptides exhibit important potential for green-life new technology and biomedical applications mostly because of their bio-friendliness and reversibility. The formation of these ordered nanostructures pertains to the synergistic effect of various intermolecular non-covalent interactions, including hydrogen-bonding, π-π stacking, electrostatic, hydrophobic, and van der Waals interactions. Therefore, the self-assembly process is mainly driven by thermodynamics; however, kinetics is also a critical factor in structural modulation and function integration. In this review, we focus on the influence of thermodynamic and kinetic factors on structural assembly and regulation based on different types of peptide building blocks, including aromatic dipeptides, amphiphilic peptides, polypeptides, and amyloid-relevant peptides.

  12. Encoded libraries of chemically modified peptides.

    PubMed

    Heinis, Christian; Winter, Greg

    2015-06-01

    The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries. Copyright © 2015. Published by Elsevier Ltd.

  13. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    PubMed Central

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P. R. O.

    2011-01-01

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a ‘preservation motif’, and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival. PMID:21687667

  14. Dinosaur peptides suggest mechanisms of protein survival.

    PubMed

    San Antonio, James D; Schweitzer, Mary H; Jensen, Shane T; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P R O

    2011-01-01

    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  15. A viral peptide for intracellular delivery

    NASA Astrophysics Data System (ADS)

    Falanga, Annarita; Tarallo, Rossella; Cantisani, Marco; Della Pepa, Maria Elena; Galdiero, Massimiliano; Galdiero, Stefania

    2012-10-01

    Biological membranes represent a critical hindrance for administering active molecules which are often unable to reach their designated intracellular target sites. In order to overcome this barrier-like behavior not easily circumvented by many pharmacologically-active molecules, synthetic transporters have been exploited to promote cellular uptake. Linking or complexing therapeutic molecules to peptides that can translocate through the cellular membranes could enhance their internal delivery, and consequently, a higher amount of active compound would reach the site of action. Use of cell penetrating peptides (CPPs) is one of the most promising strategy to efficiently translocate macromolecules through the plasma membrane, and have attracted a lot of attention. New translocating peptides are continuously described and in the present review, we will focus on viral derived peptides, and in particular a peptide (gH625) derived from the herpes simplex virus type 1 (HSV-1) glycoprotein H (gH) that has proved to be a useful delivery vehicle due to its intrinsic properties of inducing membrane perturbation.

  16. Peptide synthesis in early earth hydrothermal systems

    USGS Publications Warehouse

    Lemke, K.H.; Rosenbauer, R.J.; Bird, D.K.

    2009-01-01

    We report here results from experiments and thermodynamic calculations that demonstrate a rapid, temperature-enhanced synthesis of oligopeptides from the condensation of aqueous glycine. Experiments were conducted in custom-made hydrothermal reactors, and organic compounds were characterized with ultraviolet-visible procedures. A comparison of peptide yields at 260??C with those obtained at more moderate temperatures (160??C) gives evidence of a significant (13 kJ ?? mol-1) exergonic shift. In contrast to previous hydrothermal studies, we demonstrate that peptide synthesis is favored in hydrothermal fluids and that rates of peptide hydrolysis are controlled by the stability of the parent amino acid, with a critical dependence on reactor surface composition. From our study, we predict that rapid recycling of product peptides from cool into near-supercritical fluids in mid-ocean ridge hydrothermal systems will enhance peptide chain elongation. It is anticipated that the abundant hydrothermal systems on early Earth could have provided a substantial source of biomolecules required for the origin of life. Astrobiology 9, 141-146. ?? 2009 Mary Ann Liebert, Inc. 2009.

  17. Comprehensive computational design of ordered peptide macrocycles

    PubMed Central

    Hosseinzadeh, Parisa; Bhardwaj, Gaurav; Mulligan, Vikram Khipple; Shortridge, Matthew D.; Craven, Timothy W.; Pardo-Avila, Fátima; Rettie, Stephen A.; Kim, David E.; Silva, Daniel-Adriano; Ibrahim, Yehia M.; Webb, Ian K.; Cort, John R.; Adkins, Joshua N.; Varani, Gabriele; Baker, David

    2018-01-01

    Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent therapeutics identified to date, but there is currently no way to systematically search the structural space spanned by such compounds. Natural proteins do not provide a useful guide: Peptide macrocycles lack regular secondary structures and hydrophobic cores, and can contain local structures not accessible with L-amino acids. Here, we enumerate the stable structures that can be adopted by macrocyclic peptides composed of L- and D-amino acids by near-exhaustive backbone sampling followed by sequence design and energy landscape calculations. We identify more than 200 designs predicted to fold into single stable structures, many times more than the number of currently available unbound peptide macrocycle structures. Nuclear magnetic resonance structures of 9 of 12 designed 7- to 10-residue macrocycles, and three 11- to 14-residue bicyclic designs, are close to the computational models. Our results provide a nearly complete coverage of the rich space of structures possible for short peptide macrocycles and vastly increase the available starting scaffolds for both rational drug design and library selection methods. PMID:29242347

  18. Analogues of the Frog-skin Antimicrobial Peptide Temporin 1Tb Exhibit a Wider Spectrum of Activity and a Stronger Antibiofilm Potential as Compared to the Parental Peptide

    NASA Astrophysics Data System (ADS)

    Grassi, Lucia; Maisetta, Giuseppantonio; Maccari, Giuseppe; Esin, Semih; Batoni, Giovanna

    2017-04-01

    The frog skin-derived peptide Temporin 1Tb (TB) has gained increasing attention as novel antimicrobial agent for the treatment of antibiotic-resistant and/or biofilm-mediated infections. Nevertheless, such a peptide possesses a preferential spectrum of action against Gram-positive bacteria. In order to improve the therapeutic potential of TB, the present study evaluated the antibacterial and antibiofilm activities of two TB analogues against medically relevant bacterial species. Of the two analogues, TB_KKG6A has been previously described in the literature, while TB_L1FK is a new analogue designed by us through statistical-based computational strategies. Both TB analogues displayed a faster and stronger bactericidal activity than the parental peptide, especially against Gram-negative bacteria in planktonic form. Differently from the parental peptide, TB_KKG6A and TB_L1FK were able to inhibit the formation of Staphylococcus aureus biofilms by more than 50% at 12 μM, while only TB_KKG6A prevented the formation of Pseudomonas aeruginosa biofilms at 24 μM. A marked antibiofilm activity against preformed biofilms of both bacterial species was observed for the two TB analogues when used in combination with EDTA. Analysis of synergism at the cellular level suggested that the antibiofilm activity exerted by the peptide-EDTA combinations against mature biofilms might be due mainly to a disaggregating effect on the extracellular matrix in the case of S. aureus, and to a direct activity on biofilm-embedded cells in the case of P. aeruginosa. Both analogues displayed a low hemolytic effect at the active concentrations and, overall, TB_L1FK resulted less cytotoxic towards mammalian cells. Collectively, the results obtained demonstrated that subtle changes in the primary sequence of TB may provide TB analogues that, used alone or in combination with adjuvant molecules such as EDTA, exhibit promising features against both planktonic and biofilm cells of medically relevant

  19. Structural Insight into Recognition of Plant Peptide Hormones by Receptors.

    PubMed

    Zhang, Heqiao; Han, Zhifu; Song, Wen; Chai, Jijie

    2016-11-07

    Secreted signaling peptides or peptide hormones play crucial roles in plant growth and development through coordination of cell-cell communication. Perception of peptide hormones in plants generally relies on membrane-localized receptor kinases (RKs). Progress has recently been made in structural elucidation of interactions between posttranslationally modified peptide hormones and RKs. The structural studies suggest conserved receptor binding and activation mechanisms of this type of peptide hormones involving their conserved C-termini. Here, we review these structural data and discuss how the conserved mechanisms can be used to match peptide-RK pairs. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

  20. A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing

    PubMed Central

    Ferrante, Andrea; Gorski, Jack

    2012-01-01

    The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separates purified peptide/DR1 complexes (pDR1) into two conformers whose ratio is peptide Kd-dependent. In the absence of exchange peptide, DM only releases peptide from the slower migrating conformer. Addition of exchange peptide converts the DM-resistant conformer to the slower migrating conformer, which is DM labile. Thus, exchange peptide generates a conformer of pDR1 which constitutes the intermediate for peptide exchange and the substrate for DM activity. The resolution of the intermediate favors the highest affinity peptide. However, once folded into the DM-resistant conformer, even low affinity peptides can be presented in the absence of free peptide, broadening the repertoire available for presentation. PMID:22545194

  1. Mechanical characteristics of beta sheet-forming peptide hydrogels are dependent on peptide sequence, concentration and buffer composition

    PubMed Central

    Müller, Michael; König, Finja; Meyer, Nina; Gattlen, Jasmin; Pieles, Uwe; Peters, Kirsten; Kreikemeyer, Bernd; Mathes, Stephanie; Saxer, Sina

    2018-01-01

    Self-assembling peptide hydrogels can be modified regarding their biodegradability, their chemical and mechanical properties and their nanofibrillar structure. Thus, self-assembling peptide hydrogels might be suitable scaffolds for regenerative therapies and tissue engineering. Owing to the use of various peptide concentrations and buffer compositions, the self-assembling peptide hydrogels might be influenced regarding their mechanical characteristics. Therefore, the mechanical properties and stability of a set of self-assembling peptide hydrogels, consisting of 11 amino acids, made from four beta sheet self-assembling peptides in various peptide concentrations and buffer compositions were studied. The formed self-assembling peptide hydrogels exhibited stiffnesses ranging from 0.6 to 205 kPa. The hydrogel stiffness was mostly affected by peptide sequence followed by peptide concentration and buffer composition. All self-assembling peptide hydrogels examined provided a nanofibrillar network formation. A maximum self-assembling peptide hydrogel dissolution of 20% was observed for different buffer solutions after 7 days. The stability regarding enzymatic and bacterial digestion showed less degradation in comparison to the self-assembling peptide hydrogel dissolution rate in buffer. The tested set of self-assembling peptide hydrogels were able to form stable scaffolds and provided a broad spectrum of tissue-specific stiffnesses that are suitable for a regenerative therapy. PMID:29657766

  2. Engineered chimeric peptides with antimicrobial and titanium-binding functions to inhibit biofilm formation on Ti implants.

    PubMed

    Geng, Hongjuan; Yuan, Yang; Adayi, Aidina; Zhang, Xu; Song, Xin; Gong, Lei; Zhang, Xi; Gao, Ping

    2018-01-01

    Titanium (Ti) implants have been commonly used in oral medicine. However, despite their widespread clinical application, these implants are susceptible to failure induced by microbial infection due to bacterial biofilm formation. Immobilization of chimeric peptides with antibacterial properties on the Ti surface may be a promising antimicrobial approach to inhibit biofilm formation. Here, chimeric peptides were designed by connecting three sequences (hBD-3-1/2/3) derived from human β-defensin-3 (hBD-3) with Ti-binding peptide-l (TBP-l: RKLPDAGPMHTW) via a triple glycine (G) linker to modify Ti surfaces. Using X-ray photoelectron spectroscopy (XPS), the properties of individual domains of the chimeric peptides were evaluated for their binding activity toward the Ti surface. The antimicrobial and anti-biofilm efficacy of the peptides against initial settlers, Streptococcus oralis (S. oralis), Streptococcus gordonii (S. gordonii) and Streptococcus sanguinis (S. sanguinis), was evaluated with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Transmission electron microscopy (TEM) and real-time quantitative PCR (qRT-PCR) were used to study cell membrane changes and the underlying antimicrobial mechanism. Compared with the other two peptides, TBP-1-GGG-hBD3-3 presented stronger antibacterial activity and remained stable in saliva and serum. Therefore, it was chosen as the best candidate to modify Ti surfaces in this study. This peptide inhibited the growth of initial streptococci and biofilm formation on Ti surfaces with no cytotoxicity to MC3T3-E1 cells. Disruption of the integrity of bacterial membranes and decreased expression of adhesion protein genes from S. gordonii revealed aspects of the antibacterial mechanism of TBP-1-GGG-hBD3-3. We conclude that engineered chimeric peptides with antimicrobial activity provide a potential solution for inhibiting biofilm formation on Ti surfaces to reduce or prevent the occurrence of peri

  3. Gastrin Receptor-Avid Peptide Conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2005-07-26

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  4. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, C. A.

    2001-01-01

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  5. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Sieckman, Gary; Smith, Charles J.; Gali, Hariprasad

    2006-06-13

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a-moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  6. Gastrin receptor-avid peptide conjugates

    DOEpatents

    Hoffman, Timothy J.; Volkert, Wynn A.; Li, Ning; Sieckman, Gary; Higginbotham, Chrys-Ann

    2006-12-12

    A compound for use as a therapeutic or diagnostic radiopharmaceutical includes a group capable of complexing a medically useful metal attached to a moiety which is capable of binding to a gastrin releasing peptide receptor. A method for treating a subject having a neoplastic disease includes administering to the subject an effective amount of a radiopharmaceutical having a metal chelated with a chelating group attached to a moiety capable of binding to a gastrin releasing peptide receptor expressed on tumor cells with subsequent internalization inside of the cell. A method of forming a therapeutic or diagnostic compound includes reacting a metal synthon with a chelating group covalently linked with a moiety capable of binding a gastrin releasing peptide receptor.

  7. Antimicrobial peptides and plant disease control.

    PubMed

    Montesinos, Emilio

    2007-05-01

    Several diseases caused by viruses, bacteria and fungi affect plant crops, resulting in losses and decreasing the quality and safety of agricultural products. Plant disease control relies mainly on chemical pesticides that are currently subject to strong restrictions and regulatory requirements. Antimicrobial peptides are interesting compounds in plant health because there is a need for new products in plant protection that fit into the new regulations. Living organisms secrete a wide range of antimicrobial peptides produced through ribosomal (defensins and small bacteriocins) or non-ribosomal synthesis (peptaibols, cyclopeptides and pseudopeptides). Several antimicrobial peptides are the basis for the design of new synthetic analogues, have been expressed in transgenic plants to confer disease protection or are secreted by microorganisms that are active ingredients of commercial biopesticides.

  8. Coupling of carbon and peptide nanotubes.

    PubMed

    Montenegro, Javier; Vázquez-Vázquez, Carlos; Kalinin, Arseny; Geckeler, Kurt E; Granja, Juan R

    2014-02-12

    Two of the main types of nanotubular architectures are the single-walled carbon nanotubes (SWCNTs) and the self-assembling cyclic peptide nanotubes (SCPNs). We here report the preparation of the dual composite resulting from the ordered combination of both tubular motifs. In the resulting architecture, the SWCNTs can act as templates for the assembly of SCPNs that engage the carbon nanotubes noncovalently via pyrene "paddles", each member of the resulting hybrid stabilizing the other in aqueous solution. The particular hybrids obtained in the present study formed highly ordered oriented arrays and display complementary properties such as electrical conductivity. Furthermore, a self-sorting of the cyclic peptides toward semiconducting rather than metallic SWCNTs is also observed in the aqueous dispersions. It is envisaged that a broad range of exploitable properties may be achieved and/or controlled by varying the cyclic peptide components of similar SWCNT/SCPN hybrids.

  9. Peptide Based Radiopharmaceuticals: Specific Construct Approach

    SciTech Connect

    Som, P; Rhodes, B A; Sharma, S S

    1997-10-21

    The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures).more » In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher

  10. Melittin: a lytic peptide with anticancer properties.

    PubMed

    Gajski, Goran; Garaj-Vrhovac, Vera

    2013-09-01

    Melittin (MEL) is a major peptide constituent of bee venom that has been proposed as one of the upcoming possibilities for anticancer therapy. Recent reports point to several mechanisms of MEL cytotoxicity in different types of cancer cells such as cell cycle alterations, effect on proliferation and/or growth inhibition, and induction of apoptotic and necrotic cell death trough several cancer cell death mechanisms, including the activation of caspases and matrix metalloproteinases. Although cytotoxic to a broad spectrum of tumour cells, the peptide is also toxic to normal cells. Therefore its therapeutic potential cannot be achieved without a proper delivery vehicle which could be overcome by MEL nanoparticles that possess the ability to safely deliver significant amount of MEL intravenously, and to target and kill tumours. This review paper summarizes the current knowledge and brings latest research findings on the anticancer potential of this lytic peptide with diverse functions. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Peptides and peptidomimetics in medicine, surgery and biotechnology.

    PubMed

    Gentilucci, Luca; Tolomelli, Alessandra; Squassabia, Federico

    2006-01-01

    Despite the fact that they have been used for a century to treat several kinds of diseases, peptides and short proteins are now considered the new generation of biologically active tools. Indeed, recent findings suggest a wide range of novel applications in medicine, biotechnology, and surgery. The efficacy of native peptides has been greatly enhanced by introducing structural modifications in the original sequences, giving rise to the class of peptidomimetics. This review gives an overview of both classical applications and promising new categories of biologically active peptides and analogs. Besides the new entries in well known peptide families, such as antibiotic macrocyclic peptides, integrin inhibitors, as well as immunoactive, anticancer, neuromodulator, opioid, and hormone peptides, a number of novel applications have been recently reported. Outstanding examples include peptide-derived semi-synthetic vaccines, drug delivery systems, radiolabeled peptides, self-assembling peptides, which can serve as biomaterials in tissue engineering for creating cartilage, blood vessels, and other tissues, or as substrates for neurite outgrowth and synapse formation, immobilized peptides, and proteins. Finally, peptide-based biomaterials can find applications in bio-nanotechnology for bio-microchips, peptide nanorods and nanotubes, bio-sensors, bio-electronic devices, and peptide-metal wires.

  12. Physiological effects and therapeutic potential of proinsulin C-peptide

    PubMed Central

    Maric-Bilkan, Christine; Luppi, Patrizia; Wahren, John

    2014-01-01

    Connecting Peptide, or C-peptide, is a product of the insulin prohormone, and is released with and in amounts equimolar to those of insulin. While it was once thought that C-peptide was biologically inert and had little biological significance beyond its role in the proper folding of insulin, it is now known that C-peptide binds specifically to the cell membranes of a variety of tissues and initiates specific intracellular signaling cascades that are pertussis toxin sensitive. Although it is now clear that C-peptide is a biologically active molecule, controversy still remains as to the physiological significance of the peptide. Interestingly, C-peptide appears to reverse the deleterious effects of high glucose in some tissues, including the kidney, the peripheral nerves, and the vasculature. C-peptide is thus a potential therapeutic agent for the treatment of diabetes-associated long-term complications. This review addresses the possible physiologically relevant roles of C-peptide in both normal and disease states and discusses the effects of the peptide on sensory nerve, renal, and vascular function. Furthermore, we highlight the intracellular effects of the peptide and present novel strategies for the determination of the C-peptide receptor(s). Finally, a hypothesis is offered concerning the relationship between C-peptide and the development of microvascular complications of diabetes. PMID:25249503

  13. Development of peptide and protein based radiopharmaceuticals.

    PubMed

    Wynendaele, Evelien; Bracke, Nathalie; Stalmans, Sofie; De Spiegeleer, Bart

    2014-01-01

    Radiolabelled peptides and proteins have recently gained great interest as theranostics, due to their numerous and considerable advantages over small (organic) molecules. Developmental procedures of these radiolabelled biomolecules start with the radiolabelling process, greatly defined by the amino acid composition of the molecule and the radionuclide used. Depending on the radionuclide selection, radiolabelling starting materials are whether or not essential for efficient radiolabelling, resulting in direct or indirect radioiodination, radiometal-chelate coupling, indirect radiofluorination or (3)H/(14)C-labelling. Before preclinical investigations are performed, quality control analyses of the synthesized radiopharmaceutical are recommended to eliminate false positive or negative functionality results, e.g. changed receptor binding properties due to (radiolabelled) impurities. Therefore, radionuclidic, radiochemical and chemical purity are investigated, next to the general peptide attributes as described in the European and the United States Pharmacopeia. Moreover, in vitro and in vivo stability characteristics of the peptides and proteins also need to be explored, seen their strong sensitivity to proteinases and peptidases, together with radiolysis and trans-chelation phenomena of the radiopharmaceuticals. In vitro biomedical characterization of the radiolabelled peptides and proteins is performed by saturation, kinetic and competition binding assays, analyzing KD, Bmax, kon, koff and internalization properties, taking into account the chemical and metabolic stability and adsorption events inherent to peptides and proteins. In vivo biodistribution can be adapted by linker, chelate or radionuclide modifications, minimizing normal tissue (e.g. kidney and liver) radiation, and resulting in favorable dosimetry analyses. Finally, clinical trials are initiated, eventually leading to the marketing of radiolabelled peptides and proteins for PET/SPECT-imaging and therapy

  14. Sacubitril/valsartan: beyond natriuretic peptides.

    PubMed

    Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

    2017-10-01

    Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

  15. Dual functional bioactive-peptide, AIMP1-derived peptide (AdP), for anti-aging.

    PubMed

    Kim, Jina; Kang, Sujin; Kwon, HanJin; Moon, HoSang; Park, Min Chul

    2018-06-19

    Human skin aging is caused by several factors, such as UV irradiation, stress, hormone, and pollution. Wrinkle formation and skin pigmentation are representative features of skin aging. Although EGF and arbutin are used as anti-wrinkle and skin whitening agents, respectively, they have adverse effects on skin. When more cosmeceutical ingredients are added to cosmetic product, adverse effects are also accumulated. For these reasons, multifunctional and safe cosmetic ingredients are in demand. The aim of the present study is to investigate the novel anti-aging agents, AIMP1-derived peptide (AdP, INCI name: sh-oligopeptide-5/sh-oligopeptide SP) for cosmetic products. To assess the anti-wrinkle effect of AdP, collagen type I synthesis and fibroblast proliferation were determined on human fibroblasts. The anti-wrinkle effect of AdP was examined by ELISA and cell titer glo assay. To assess the whitening, melanin content and tyrosinase activity were determined on melanocytes. The whitening effect of AdP was examined by melanin measurement and enzyme activity assay. The safety of AdP was determined by cytotoxicity and immunogenicity, CCK-8 and TNF-α ELISA assay, respectively. AdP treatment induced the collagen type I synthesis and fibroblast proliferation. Also, AdP treatment inhibited melanin synthesis by regulating tyrosinase activity. The anti-aging effect of AdP is more potent than EGF and albutin. AdP did not show adverse effects. These results show that AdP can be dual functional and safe cosmeceutical agent to prevent skin aging. © 2018 Wiley Periodicals, Inc.

  16. Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.

    PubMed

    Noguchi, Masanori; Koga, Noriko; Moriya, Fukuko; Suekane, Shigetaka; Yutani, Shigeru; Yamada, Akira; Shichijo, Shigeki; Kakuma, Tatuyuki; Itoh, Kyogo

    2018-06-25

    Peptide-based cancer vaccines are able to induce strong immune responses, but their clinical results are unsatisfactory. To determine clinically correlated peptides, we analyzed survival data from urological cancer patients treated by personalized peptide vaccination (PPV), in which different multiple peptides were used for individual patients based on human leukocyte antigen (HLA) type and pre-existing immunity. Survival data were obtained from a database of 265 urological cancer patients treated in 5 clinical PPV trials comprising 154 patients with castration-resistant prostate cancer (CRPC) and 111 patients with advanced urothelial cancer (UC). The expression of tumor-associated antigens (TAAs) was evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate cancer and 10 UC tissues using immunohistochemical staining. The clinical efficacy of individual peptides for overall survival was evaluated by the Cox proportional hazards regression model. All TAAs coding candidate peptides used in PPV treatment were expressed in tumor cells from prostate cancer and UC samples except for p56Lck in both, and PSA, PAP and PSMA in the UC samples. Patients with the following peptides had a significantly longer survival than patients without the peptides (Hazard ratio < 1.0, 95% confidence intervals < 1.0 and P < 0.05): SART3-109, PTHrP-102, HNPRL-140, SART3-302 and Lck-90 in CRPC patients, and EGF-R-800, Lck-486, PSMA-624, CypB-129 and SART3-734 in advanced UC patients, respectively. Correlated peptides selected using both survival data and pre-existing immunity for PPV treatment may enhance the clinical benefits for urological cancer patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  17. Advances in macrocyclic peptide-based antibiotics.

    PubMed

    Luther, Anatol; Bisang, Christian; Obrecht, Daniel

    2018-06-01

    Macrocyclic peptide-based natural products have provided powerful new antibiotic drugs, drug candidates, and scaffolds for medicinal chemists as a source of inspiration to design novel antibiotics. While most of those natural products are active mainly against Gram-positive pathogens, novel macrocyclic peptide-based compounds have recently been described, which exhibit potent and specific activity against some of the most problematic Gram-negative ESKAPE pathogens. This mini-review gives an up-date on recent developments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Calcitonin and Amylin Receptor Peptide Interaction Mechanisms

    PubMed Central

    Lee,