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Sample records for molecular weight inhibitors

  1. A low molecular weight proteinase inhibitor produced by T lymphocytes.

    PubMed Central

    Ganea, D; Teodorescu, M; Dray, S

    1986-01-01

    A low molecular weight (MW) proteinase inhibitor, between 6500 and 21,500 MW, appeared in the supernatant of rabbit spleen cells cultured at high density for 24 hr. The inhibitor inhibited the enzymatic activity of trypsin for both a high MW natural substrate, fibrinogen, and for a low MW artificial substrate, Chromozym TRY. The low MW proteinase inhibitor is protein in nature and is different, in terms of specificity for enzymes, MW and sensitivity to different physical or chemical treatments, from aprotinin, a low MW proteinase inhibitor (6500 MW) of bovine origin, and from the soybean trypsin inhibitor, a relatively high MW proteinase inhibitor (21,500 MW). The inhibitor was found in the supernatant of purified T cells but not B cells, and its production was increased in the presence of an optimal concentration of Con A. The possibility that this proteinase inhibitor has a role in the regulation of trypsin-like proteinases involved to the immune response remains to be investigated. Images Figure 4 PMID:2417942

  2. New cyanopeptide-derived low molecular weight thrombin inhibitors.

    PubMed

    Radau, Gregor; Gebel, Jana; Rauh, Daniel

    2003-08-01

    Thrombosis is the result of defective regulation of the hemostasis system. This cardiovascular disorder may lead to deep vein thrombosis, myocardial infarction, and stroke. The majority of current drug research is focused on finding inhibitors of thrombin - the global player in hemostasis. In our work, we emphasize investigation of the marine environment to yield new lead structures from marine organisms like blue-green algae (cyanobacteria). This article deals with the design, syntheses, and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98-B (2) as a lead structure, we have developed and synthesized new, selective acting inhibitors of thrombin (RA-1001 and RA-1002), which are suitable targets for further structure-activity studies.

  3. Tyrosine kinase inhibitors - small molecular weight compounds inhibiting EGFR.

    PubMed

    Hegymegi-Barakonyi, Bálint; Eros, Dániel; Szántai-Kis, Csaba; Breza, Nóra; Bánhegyi, Péter; Szabó, Gábor Viktor; Várkondi, Edit; Peták, István; Orfi, László; Kéri, György

    2009-06-01

    Abnormally elevated EGFR kinase activity can lead to various pathological states, including proliferative diseases such as cancer. The development of selective protein kinase inhibitors has become an important area of drug discovery for the potential treatment of a variety of solid tumors such as breast, ovarian and colorectal cancers, NSCLC, and carcinoma of the head and neck. There are three small molecule EGFR kinase inhibitor drugs in clinical use (gefitinib, erlotinib and lapatinib), and several others are currently undergoing clinical development. This review summarizes the development of EGFR kinase inhibitors, and includes descriptions of the binding modes, the importance of a multiple-targets strategy, the effects of sensitizing and resistance mutations in the EGFR, and molecular diagnostic approaches. In addition, the use of target fishing for selectivity profiling, off-target identification and quantitative structure-activity relationship modeling for the prediction of EGFR inhibition is discussed.

  4. Targeting cancer with small-molecular-weight kinase inhibitors.

    PubMed

    Fabbro, Doriano; Cowan-Jacob, Sandra W; Möbitz, Henrik; Martiny-Baron, Georg

    2012-01-01

    Protein and lipid kinases fulfill essential roles in many signaling pathways that regulate normal cell functions. Deregulation of these kinase activities lead to a variety of pathologies ranging from cancer to inflammatory diseases, diabetes, infectious diseases, cardiovascular disorders, cell growth and survival. 518 protein kinases and about 20 lipid-modifying kinases are encoded by the human genome, and a much larger proportion of additional kinases are present in parasite, bacterial, fungal, and viral genomes that are susceptible to exploitation as drug targets. Since many human diseases result from overactivation of protein and lipid kinases due to mutations and/or overexpression, this enzyme class represents an important target for the pharmaceutical industry. Approximately one third of all protein targets under investigation in the pharmaceutical industry are protein or lipid kinases.The kinase inhibitors that have been launched, thus far, are mainly in oncology indications and are directed against a handful of protein and lipid kinases. With one exception, all of these registered kinase inhibitors are directed toward the ATP-site and display different selectivities, potencies, and pharmacokinetic properties. At present, about 150 kinase-targeted drugs are in clinical development and many more in various stages of preclinical development. Kinase inhibitor drugs that are in clinical trials target all stages of signal transduction from the receptor protein tyrosine kinases that initiate intracellular signaling, through second-messenger-dependent lipid and protein kinases, and protein kinases that regulate the cell cycle.This review provides an insight into protein and lipid kinase drug discovery with respect to achievements, binding modes of inhibitors, and novel avenues for the generation of second-generation kinase inhibitors to treat cancers.

  5. New cyanopeptide-derived low molecular weight inhibitors of trypsin-like serine proteases.

    PubMed

    Radau, Gregor; Schermuly, Sonja; Fritsche, Alexandra

    2003-08-01

    This paper deals with the design, syntheses, and inhibition tests of new low molecular weight thrombin inhibitors utilizing cyanopeptides, the secondary metabolites of cyanobacteria with interesting biological activities, as new lead structures. Starting with aeruginosin 98-B (1) as a lead structure, we have developed and synthesised new, selective acting inhibitors of serine proteases (RA-1005 and RA-1009, which are suitable targets for further structure-activity studies.

  6. Low molecular weight serine protease inhibitors from insects are proteins with highly conserved sequences.

    PubMed

    Boigegrain, R A; Pugnière, M; Paroutaud, P; Castro, B; Brehélin, M

    2000-02-01

    A low molecular weight protease inhibitor peptide found in ovaries of the desert locust Schistocerca gregaria (SGPI-2), was purified from plasma of the same locust and sequenced. It was named SGCI. It was found active towards chymotrypsin and human leukocyte elastase. SGCI was synthesized using a solid-phase procedure and the sequence of its reactive site for chymotrypsin was determined. Compared with an inhibitor purified earlier from another locust species, the total sequence of SGCI showed 88% identity. In particular, the sequence of the reactive site of these inhibitors was identical. Our search for a closely related peptide in an insect species far removed from locusts, the lepidopteran Spodoptera littoralis, was unfruitful but a different chymotrypsin inhibitor, belonging to the Kazal family, was found whose mass is greater than that of SGCI (20 vs 3.6 kDa). Its N-terminal sequence shares 80% identity with that of a chymotrypsin inhibitor purified earlier from the haemolymph of another lepidopteran. Conservation of the amino acid sequence in the reactive site seems to be an exception among protease inhibitors.

  7. Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.

    PubMed

    Yadav, Vikash Kumar; Chhikara, Nirmal; Gill, Kamaldeep; Dey, Sharmistha; Singh, Sarman; Yadav, Savita

    2013-08-01

    The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research.

  8. Finding of the Low Molecular Weight Inhibitors of Resuscitation Promoting Factor Enzymatic and Resuscitation Activity

    PubMed Central

    Demina, Galina R.; Makarov, Vadim A.; Nikitushkin, Vadim D.; Ryabova, Olga B.; Vostroknutova, Galina N.; Salina, Elena G.; Shleeva, Margarita O.; Goncharenko, Anna V.; Kaprelyants, Arseny S.

    2009-01-01

    Background Resuscitation promoting factors (RPF) are secreted proteins involved in reactivation of dormant actinobacteria, including Mycobacterium tuberculosis. They have been considered as prospective targets for the development of new anti-tuberculosis drugs preventing reactivation of dormant tubercle bacilli, generally associated with latent tuberculosis. However, no inhibitors of Rpf activity have been reported so far. The goal of this study was to find low molecular weight compounds inhibiting the enzymatic and biological activities of Rpfs. Methodology/Principal Findings Here we describe a novel class of 2-nitrophenylthiocyanates (NPT) compounds that inhibit muralytic activity of Rpfs with IC50 1–7 µg/ml. Fluorescence studies revealed interaction of active NPTs with the internal regions of the Rpf molecule. Candidate inhibitors of Rpf enzymatic activity showed a bacteriostatic effect on growth of Micrococcus luteus (in which Rpf is essential for growth protein) at concentrations close to IC50. The candidate compounds suppressed resuscitation of dormant (“non-culturable”) cells of M. smegmatis at 1 µg/ml or delayed resuscitation of dormant M. tuberculosis obtained in laboratory conditions at 10 µg/ml. However, they did not inhibit growth of active mycobacteria under these concentrations. Conclusions/Significance NPT are the first example of low molecular weight compounds that inhibit the enzymatic and biological activities of Rpf proteins. PMID:20016836

  9. Ex vivo inhibition of Clostridium botulinum neurotoxin types B, C, E, and F by small molecular weight inhibitors.

    PubMed

    Montgomery, Vicki A; Ahmed, S Ashraf; Olson, Mark A; Mizanur, Rahman M; Stafford, Robert G; Roxas-Duncan, Virginia I; Smith, Leonard A

    2015-05-01

    Two small molecular weight inhibitors, compounds CB7969312 and CB7967495, that displayed inhibition of botulinum neurotoxin serotype A in a previous study, were evaluated for inhibition of botulinum neurotoxin serotypes B, C, E, and F. The small molecular weight inhibitors were assessed by molecular modeling, UPLC-based peptide cleavage assay; and an ex vivo assay, the mouse phrenic nerve - hemidiaphragm assay (MPNHDA). While both compounds were inhibitors of botulinum neurotoxin (BoNT) serotypes B, C, and F in the MPNHDA, compound CB7969312 was effective at lower molar concentrations than compound CB7967495. However, compound CB7967495 was significantly more effective at preventing BoNTE intoxication than compound CB7969312. In the UPLC-based peptide cleavage assay, CB7969312 was also more effective against LcC. Both compounds inhibited BoNTE, but not BoNTF, LcE, or LcF in the UPLC-based peptide cleavage assay. Molecular modeling studies predicted that both compounds would be effective inhibitors of BoNTs B, C, E, and F. But CB7967495 was predicted to be a more effective inhibitor of the four serotypes (B, C, E, and F) than CB7969312. This is the first report of a small molecular weight compound that inhibits serotypes B, C, E, and F in the ex vivo assay.

  10. Low molecular weight inhibitors of Myc-Max interaction and function.

    PubMed

    Yin, Xiaoying; Giap, Christine; Lazo, John S; Prochownik, Edward V

    2003-09-18

    c-Myc is helix-loop-helix-leucine zipper (HLH-ZIP) oncoprotein that is frequently deregulated in human cancers. In order to bind DNA, regulate target gene expression, and function in a biological context, c-Myc must dimerize with another HLH-ZIP protein, Max. A large number of c-Myc target genes have been identified, and many of the encoded proteins are transforming. Such functional redundancy, however, complicates therapeutic strategies aimed at inhibiting any single target gene product. Given this consideration, we have instead attempted to identify ways by which c-Myc itself could be effectively disabled. We have used a yeast two-hybrid approach to identify low-molecular-weight compounds that inhibit c-Myc-Max association. All of the compounds prevented transactivation by c-Myc-Max heterodimers, inhibited cell cycle progression, and prevented the in vitro growth of fibroblasts in a c-Myc-dependent manner. Several of the compounds also inhibited tumor growth in vivo. These results show that the yeast two-hybrid screen is useful for identifying compounds that can be exploited in mammalian cells. More specifically, they provide a means by which structural analogs, based upon these first-generation Myc-Max inhibitors, can be developed to enhance antitumor efficacy.

  11. Glycoprotein IIb/IIIa inhibitors and low-molecular-weight heparins: a combined role in coronary interventions?

    PubMed

    Fry, E T

    2001-03-01

    Management strategies for acute coronary syndromes (ACS) are making increasing use of both low-molecular-weight heparins (LMWHs) and glycoprotein (GP) IIb/IIIa inhibitors. To date, however, relatively few studies have assessed the clinical potential of these two classes of agents in combination. There are theoretical grounds to expect LMWHs to be more effective than unfractionated heparin (UFH) in combination with GP IIb/IIIa inhibitors, since UFH, but not LMWH, activates platelets. The antiplatelet effects of GP IIb/IIIa inhibitors are therefore likely to be both more potent and more predictable when combined with LMWH. A recent study in more than 100 patients has demonstrated that a combination of dalteparin and the GP IIb/IIIa inhibitor abciximab provided effective anticoagulation in patients undergoing percutaneous coronary intervention (PCI), without causing significant bleeding or adverse events. Similar results were demonstrated in the National Investigators Collaborating on Enoxaparin (NICE-4) study using a combination of abciximab and enoxaparin in patients undergoing PCI. Of importance is the fact that there were no cases of severe thrombocytopenia in either LMWH study, although this is a recognized potential complication when UFH and abciximab are used in combination. Further studies are now warranted to confirm the efficacy of LMWH and GP IIb/IIIa inhibitors in combination, both for PCI and medical stabilization.

  12. Discovery of Sanggenon G as a natural cell-permeable small-molecular weight inhibitor of X-linked inhibitor of apoptosis protein (XIAP).

    PubMed

    Seiter, Maximilian A; Salcher, Stefan; Rupp, Martina; Hagenbuchner, Judith; Kiechl-Kohlendorfer, Ursula; Mortier, Jérémie; Wolber, Gerhard; Rollinger, Judith M; Obexer, Petra; Ausserlechner, Michael J

    2014-01-01

    Defects in the regulation of apoptosis are one main cause of cancer development and may result from overexpression of anti-apoptotic proteins such as the X-linked inhibitor of apoptosis protein (XIAP). XIAP is frequently overexpressed in human leukemia and prostate and breast tumors. Inhibition of apoptosis by XIAP is mainly coordinated through direct binding to the initiator caspase-9 via its baculovirus-IAP-repeat-3 (BIR3) domain. XIAP inhibits caspases directly making it to an attractive target for anti-cancer therapy. In the search for novel, non-peptidic XIAP inhibitors in this study we focused on the chemical constituents of sāng bái pí (mulberry root bark). Most promising candidates of this plant were tested biochemically in vitro by a fluorescence polarization (FP) assay and in vivo via protein fragment complementation analysis (PCA). We identified the Diels Alder adduct Sanggenon G (SG1) as a novel, small-molecular weight inhibitor of XIAP. As shown by FP and PCA analyses, SG1 binds specifically to the BIR3 domain of XIAP with a binding affinity of 34.26 μM. Treatment of the transgenic leukemia cell line Molt3/XIAP with SG1 enhances caspase-8, -3 and -9 cleavage, displaces caspase-9 from XIAP as determined by immunoprecipitation experiments and sensitizes these cells to etoposide-induced apoptosis. SG1 not only sensitizes the XIAP-overexpressing leukemia cell line Molt3/XIAP to etoposide treatment but also different neuroblastoma cell lines endogenously expressing high XIAP levels. Taken together, Sanggenon G (SG1) is a novel, natural, non-peptidic, small-molecular inhibitor of XIAP that can serve as a starting point to develop a new class of improved XIAP inhibitors.

  13. Presence of a low molecular weight endogenous inhibitor on 3H-muscimol binding in synaptic membranes

    NASA Astrophysics Data System (ADS)

    Yoneda, Yukio; Kuriyama, Kinya

    1980-06-01

    The specific binding of 3H-muscimol to synaptic membrane preparations obtained from the rat brain has been thought to reflect the association of γ-aminobutyric acid (GABA), a potential candidate as an inhibitory neurotransmitter in the mammalian central nervous system (CNS), with its synaptic receptors1,2. Treatment of synaptic membranes with Triton X-100 significantly increases the specific binding of 3H-muscimol2. Several reports also indicate the presence of endogenous substances, such as GABA3, acidic protein4 and phosphatidylethanolamine5, which inhibit Na-independent binding of 3H-GABA in the synaptic membranous fractions from the rat brain. We report here that in the supernatant obtained from Triton-treated synaptic membranes there exists a new type of endogenous inhibitor of 3H-muscimol binding which is apparently different from the inhibitory substances described previously3-5. The new inhibitor has a low molecular weight (MW) and probably originated from neurones rather than glial cells. We have termed this endogenous inhibitor the GABA receptor binding inhibitory factor (GRIF).

  14. Low Molecular Weight Amidoximes that Act as Potent Inhibitors of Lysine-Specific Demethylase 1

    PubMed Central

    Hazeldine, Stuart; Pachaiyappan, Boobalan; Steinbergs, Nora; Nowotarski, Shannon; Hanson, Allison S.; Casero, Robert A.; Woster, Patrick M.

    2012-01-01

    The recently discovered enzyme lysine-specific demethylase 1 (LSD1) plays an important role in the epigenetic control of gene expression, and aberrant gene silencing secondary to LSD1 dysregulation is thought to contribute to the development of cancer. We reported that (bis)guanidines, (bis)biguanides and their urea- and thiourea isosteres are potent inhibitors of LSD1, and induce the re-expression of aberrantly silenced tumor suppressor genes in tumor cells in vitro. We now report a series of small molecule amidoximes that are moderate inhibitors of recombinant LSD1, but that produce dramatic changes in methylation at the histone 3 lysine 4 (H3K4) chromatin mark, a specific target of LSD1, in Calu-6 lung carcinoma cells. In addition, these analogues increase cellular levels of secreted frizzle-related protein (SFRP) 2, H-cadherin (HCAD) and transcription factor GATA4. These compounds represent leads for an important new series of drug-like epigenetic modulators with the potential for use as antitumor agents. PMID:22876979

  15. Efficacy of unfractionated heparin, low molecular weight heparin and both combined for releasing total and free tissue factor pathway inhibitor.

    PubMed

    Altman, R; Scazziota, A; Rouvier, J

    1998-01-01

    Unfractionated heparin (UFH) exerts its anticoagulant properties by increasing the inactivation of thrombin and activated factor X by antithrombin III. Apart from this main action release of tissue factor pathway inhibitor (TFPI) from endothelial cells could also be important for the antithrombotic activity of heparins. Four different heparin preparations were injected subcutaneously into 5 healthy volunteers 1 week apart: (1) UFH 2,500 IU fix dose (FixUFH), (2) 1 mg/kg body weight of low molecular weight heparin (LMWH), (3) the combined LMWH-adjusted dose plus UFH 2,500 IU fix dose (ComHep) and (4) UFH 2,500 IU/10 kg body weight (UFHvar). Plasma samples were drawn before and 1, 2, 4, 6, 12 and 24 h afterwards. FixUFH did not affect the concentration of total and free TFPI. Total TFPI increased in the 1st hour after LMWH injection from 74 to 124 ng/ml (p < 0.01), after ComHep from 82 to 144 ng/ml (p < 0.01), and after UFHvar from 91 to 113 ng/ml (p < 0.05). All observed elevations were significant at the peak value (+/- 2 h, p < 0.01 compared with baselines). The increase of free TFPI produced by UFHvar (74.5 and 70.5 ng/ml) was significantly higher than with LMWH (42.8 and 38.0 ng/ml) at 2 and 4 h (p < 0.001 and p < 0.01, respectively). UFHvar and ComHep but not LMWH produced a statistically significant increase of free TFPI compared with FixUFH at 2, 4 and 6 h (p < 0. 01). We concluded that at comparable therapeutic doses, subcutaneous UFHvar released more free TFPI than LMWH and ComHep. A synergism between LMWH and low dose of UFH was found in 4-, 6- and 12-hour blood samples.

  16. FGFR Inhibitor Ameliorates Hypophosphatemia and Impaired Engrailed-1/Wnt Signaling in FGF2 High Molecular Weight Isoform Transgenic Mice.

    PubMed

    Du, Erxia; Xiao, Liping; Hurley, Marja M

    2016-09-01

    High molecular weight FGF2 transgenic (HMWTg) mouse phenocopies the Hyp mouse, homolog of human X-linked hypophosphatemic rickets with hypophosphatemis, and abnormal FGF23, FGFR, Klotho signaling in kidney. Since abnormal Wnt signaling was reported in Hyp mice we assessed whether Wnt signaling was impaired in HMWTg kidneys and the effect of blocking FGF receptor (FGFR) signaling. Bone mineral density and bone mineral content in female HMWTg mice were significantly reduced. HMWTg mice were gavaged with FGFR inhibitor NVP-BGJ398, or vehicle and were euthanized 24 h post treatment. Serum phosphate was significantly reduced and urine phosphate was significantly increased in HMWTg and was rescued by NVP-BGJ398. Analysis of kidneys revealed a significant reduction in Npt2a mRNA in HMWTg that was significantly increased by NVP-BGJ398. Increased FGFR1, KLOTHO, P-ERK1/2, and decreased NPT2a protein in HMWTg were rescued by NVP-BGJ398. Wnt inhibitor Engrailed-1 mRNA and protein was increased in HMWTg and was decreased by BGJ398. Akt mRNA and protein was decreased in HMWTg and was increased by NVP-BGJ398. The active form of glycogen synthase 3 beta (pGSK3-β) and phosphor-β-catenin were increased in HMWTg and were both decreased by NVP-BGJ398 while decreased active-β-catenin in HMWTg was increased by NVP-BGJ398. We conclude that FGFR blockade rescued hypophosphatemia by regulating FGF and WNT signaling in HMWTg kidneys. J. Cell. Biochem. 117: 1991-2000, 2016. © 2016 Wiley Periodicals, Inc.

  17. Preparation and characterization of dipyridamole solid dispersions for stabilization of supersaturation: effect of precipitation inhibitors type and molecular weight.

    PubMed

    Vora, Chintan; Patadia, Riddhish; Mittal, Karan; Mashru, Rajashree

    2016-11-01

    Dipyridamole (DPL) is a weakly basic BCS class II drug which precipitates upon entering into intestine leading to pH dependant and variable absorption. Thus, research envisaged focuses on developing formulations that maintain supersaturation following upon acid to neutral pH transition. In an endeavor to accomplish the objective, solid dispersion (SD) with hydroxypropylmethyl cellulose (HPMC) and polyvinylpyrrolidone (PVP) was prepared by a quench cooling method. The three molecular weight grades of HPMC (HPMC E5, HPMC E15 and HPMC E50) and two molecular weight grades of PVP (PVP K30 and PVP K90) were investigated to observe effect of increasing molecular weight on stabilizing DPL supersaturated solutions. Equilibrium solubility studies revealed increase in solubility with both HPMC and PVP with greater benefit from HPMC. In vitro supersaturated dissolution results demonstrated that HPMC formulations provided greater degree and extent of supersaturation as compared to PVP formulations. The formulation with HPMC E50 provided maximum stabilization to supersaturation upon acid to neutral pH transition. Moreover, the effect of increase in molecular weight was more pronounced in HPMC rather than PVP. Stronger interactions were observed for DPL with HPMC, while no interaction was observed with PVP which was evident from Fourier transform infra-red studies. Differential scanning calorimetry and powder X-ray diffraction studies revealed the amorphous state of DPL in SD.

  18. Clinical benefit of low molecular weight heparin for ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention with glycoprotein IIb/IIIa inhibitor.

    PubMed

    Cho, Jung Sun; Her, Sung-Ho; Baek, Ju Yeal; Park, Mahn-Won; Kim, Hyoung Doo; Jeong, Myung Ho; Ahn, Young keun; Chae, Shung Chull; Hur, Seung Ho; Hong, Taek Jong; Kim, Young Jo; Seong, In Whan; Chae, Jei Keon; Rhew, Jay Young; Chae, In Ho; Cho, Myeong Chan; Bae, Jang Ho; Rha, Seung Woon; Kim, Chong Jim; Choi, Donghoon; Jang, Yang Soo; Yoon, Junghan; Chung, Wook Sung; Cho, Jeong Gwan; Seung, Ki Bae; Park, Seung Jung

    2010-11-01

    The efficacy of low molecular weight heparin (LMWH) with low dose unfractionated heparin (UFH) during percutaneous coronary intervention (PCI) with or without glycoprotein (Gp) IIb/IIIa inhibitor compared to UFH with or without Gp IIb/IIIa inhibitor has not been elucidated. Between October 2005 and July 2007, 2,535 patients with ST elevation acute myocardial infarction (STEMI) undergoing PCI in the Korean Acute Myocardial Infarction Registry (KAMIR) were assigned to either of two groups: a group with Gp IIb/IIIa inhibitor (n=476) or a group without Gp IIb/IIIa inhibitor (n=2,059). These groups were further subdivided according to the use of LMWH with low dose UFH (n=219) or UFH alone (n=257). The primary end points were cardiac death or myocardial infarction during the 30 days after the registration. The primary end point occurred in 4.1% (9/219) of patients managed with LMWH during PCI and Gp IIb/IIIa inhibitor and 10.8% (28/257) of patients managed with UFH and Gp IIb/IIIa inhibitor (odds ratio [OR], 0.290; 95% confidence interval [CI], 0.132-0.634; P=0.006). Thrombolysis In Myocardial Infarction (TIMI) with major bleeding was observed in LMHW and UFH with Gp IIb/IIIa inhibitor (1/219 [0.5%] vs 1/257 [0.4%], P=1.00). For patients with STEMI managed with a primary PCI and Gp IIb/IIIa inhibitor, LMWH is more beneficial than UFH.

  19. Low-molecular-weight dextran derivatives (f-CMDB) enter the nucleus and are better cell-growth inhibitors compared with parent CMDB polymers.

    PubMed

    Bittoun, P; Avramoglou, T; Vassy, J; Crépin, M; Chaubet, F; Fermandjian, S

    1999-12-12

    Carboxymethyldextrans-benzylamide (CMDB) are dextran derivatives that are statistically substituted with carboxymethyl and benzylamide groups. These molecules display a variety of biological effects, one of which is their inhibitory activity against mammary tumor cell growth, both in vitro and in vivo. We and others have previously shown that the effects of CMDB on cell growth are related to their ability to interact with the growth factor FGF-2. The binding modifies the conformation of FGF-2, leading to the suppression of its mitogenic activity. Here, the method previously reported to fragment natural polysaccharide fucans has been applied to CMDB (80,000 g/mol). f-CMDB (fragmented CMDB) of molecular weights from 6000 to 20,000 g/mol were found to be more potent inhibitors of MCF7 mammary tumor cell growth than high-molecular-weight CMDB. Confocal microscopy experiments using CMDB and f-CMDB labeled with the fluorophore DTAF (5-([4,6-dichlorotriazine-2-yl]amino) fluorescein) indicate that only low-molecular-weight f-CMDB penetrate into the nucleus of MCF7 cells. It is thus assumed that the better inhibitory properties demonstrated by f-CMDB, compared with CMDB, are related to their better ability to penetrate the nucleus and interact with nuclear targets, including topoisomerase II. The DNA relaxation properties of the latter are inhibited in vitro by both CMDB and f-CMDB. These findings could help us to develop models of low-molecular-weight oligosaccharide derivatives exhibiting better antiproliferative and antitumor properties.

  20. Structures of Human Cyctochrome P450 2E1: Insights Into the Binding of Inhibitors And Both Small Molecular Weight And Fatty Acid Substrates

    SciTech Connect

    Porubsky, P.R.; Meneely, K.M.; Scott, E.E.

    2009-05-21

    Human microsomal cytochrome P-450 2E1 (CYP2E1) monooxygenates >70 low molecular weight xenobiotic compounds, as well as much larger endogenous fatty acid signaling molecules such as arachidonic acid. In the process, CYP2E1 can generate toxic or carcinogenic compounds, as occurs with acetaminophen overdose, nitrosamines in cigarette smoke, and reactive oxygen species from uncoupled catalysis. Thus, the diverse roles that CYP2E1 has in normal physiology, toxicity, and drug metabolism are related to its ability to metabolize diverse classes of ligands, but the structural basis for this was previously unknown. Structures of human CYP2E1 have been solved to 2.2 {angstrom} for an indazole complex and 2.6 {angstrom} for a 4-methylpyrazole complex. Both inhibitors bind to the heme iron and hydrogen bond to Thr{sup 303} within the active site. Complementing its small molecular weight substrates, the hydrophobic CYP2E1 active site is the smallest yet observed for a human cytochrome P-450. The CYP2E1 active site also has two adjacent voids: one enclosed above the I helix and the other forming a channel to the protein surface. Minor repositioning of the Phe{sup 478} aromatic ring that separates the active site and access channel would allow the carboxylate of fatty acid substrates to interact with conserved {sup 216}QXXNN{sup 220} residues in the access channel while positioning the hydrocarbon terminus in the active site, consistent with experimentally observed {omega}-1 hydroxylation of saturated fatty acids. Thus, these structures provide insights into the ability of CYP2E1 to effectively bind and metabolize both small molecule substrates and fatty acids.

  1. Molecular Weight and Molecular Weight Distributions in Synthetic Polymers.

    ERIC Educational Resources Information Center

    Ward, Thomas Carl

    1981-01-01

    Focuses on molecular weight and molecular weight distributions (MWD) and models for predicting MWD in a pedagogical way. In addition, instrumental methods used to characterize MWD are reviewed with emphasis on physical chemistry of each, including end-group determination, osmometry, light scattering, solution viscosity, fractionation, and…

  2. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation.

    PubMed

    Stokol, Tracy; Serpa, Priscila Beatriz da Silva; Zahid, Muhammad N; Brooks, Marjory B

    2016-01-01

    Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins) or platelet inhibitors that impede post-receptor thrombin signaling [phosphodiesterase (PDE) antagonists] would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma (PRP) collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque-forming unit/cell in the presence or absence of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX), and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1-0.2 U/mL anti-factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM, but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX) or isoenzyme-3 selective (cilostazol) PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  3. Unfractionated and Low-Molecular-Weight Heparin and the Phosphodiesterase Inhibitors, IBMX and Cilostazol, Block Ex Vivo Equid Herpesvirus Type-1-Induced Platelet Activation

    PubMed Central

    Stokol, Tracy; Serpa, Priscila B. S.; Zahid, Muhammad N.; Brooks, Marjory B.

    2016-01-01

    Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin generation. We hypothesized that coagulation inhibitors that suppress thrombin generation (heparins) or platelet inhibitors that impede post-receptor thrombin signaling [phosphodiesterase (PDE) antagonists] would inhibit EHV-1-induced platelet activation ex vivo. We exposed platelet-rich plasma (PRP) collected from healthy horses to the RacL11 abortigenic and Ab4 neuropathogenic strains of EHV-1 at 1 plaque-forming unit/cell in the presence or absence of unfractionated heparin (UFH), low-molecular-weight heparin (LMWH) or the PDE inhibitors, 3-isobutyl-1methylxanthine (IBMX), and cilostazol. We assessed platelet activation status in flow cytometric assays by measuring P-selectin expression. We found that all of the inhibitors blocked EHV-1- and thrombin-induced platelet activation in a dose-dependent manner. Platelet activation in PRP was maximally inhibited at concentrations of 0.05 U/mL UFH and 2.5 μg/mL LMWH. These concentrations represented 0.1–0.2 U/mL anti-factor Xa activity measured in chromogenic assays. Both IBMX and cilostazol showed maximal inhibition of platelet activation at the highest tested concentration of 50 μM, but inhibition was lower than that seen with UFH and LMWH. Our results indicate that heparin anticoagulants and strong non-selective (IBMX) or isoenzyme-3 selective (cilostazol) PDE antagonists inhibit ex vivo EHV-1-induced platelet activation

  4. A supersulfated low-molecular-weight heparin (IK-SSH) increases plasma levels of free and total tissue factor pathway inhibitor after intravenous and subcutaneous administration in humans.

    PubMed

    Kaiser, B; Glusa, E; Hoppensteadt, D A; Breddin, H K; Amiral, J; Fareed, J

    1998-09-01

    Unfractionated as well as low-molecular-weight heparins (LMWH) are known to cause an increase in blood levels of tissue factor pathway inhibitor (TFPI). To study the effect of a newly developed supersulfated LMWH (IK-SSH, Iketon Farmaceutici) on TFPI concentrations in human plasma, the compound was injected into volunteers at doses of 0.14, 0.33 and 0.66 mg/kg intravenously or 0.33, 0.66 and 1.0 mg/kg subcutaneously. At certain known times blood was drawn and plasma levels of both total and free TFPI were measured using enzyme-linked immunosorbent assay methodology. Baseline plasma concentrations of TFPI were 72.2+/-3.1 ng/ml for total and 10.8+/-0.8 ng/ml for free TFPI. Intravenous or subcutaneous injection of IK-SSH led to a strong and long-lasting rise in TFPI levels which were increased more than 5-fold for total TFPI and more than 30-fold for free TFPI. Maximum TFPI levels were reached 5-10 min after intravenous and 60 min after subcutaneous administration. IK-SSH caused prolongation of ex-vivo clotting times in the APTT and Heptest assay, whereas thrombin time was not affected. Anticoagulant actions of IK-SSH showed a significant correlation to plasma concentrations of TFPI and they are thought to be based at least partially on the release of TFPI from vascular sites.

  5. Apparatus for molecular weight separation

    DOEpatents

    Smith, Richard D.; Liu, Chuanliang

    2001-01-01

    The present invention relates generally to an apparatus and method for separating high molecular weight molecules from low molecular weight molecules. More specifically, the invention relates to the use of microdialysis for removal of the salt (low molecular weight molecules) from a nucleotide sample (high molecular weight molecules) for ESI-MS analysis. The dialysis or separation performance of the present invention is improved by (1) increasing dialysis temperature thereby increasing desalting efficiency and improving spectrum quality; (2) adding piperidine and imidazole to the dialysis buffer solution and reducing charge states and further increasing detection sensitivity for DNA; (3) using low concentrations (0-2.5 mM NH4OAc) of dialysis buffer and shifting the DNA negative ions to higher charge states, producing a nearly 10-fold increase in detection sensitivity and a slightly decreased desalting efficiency, (4) conducting a two-stage separation or (5) any combination of (1), (2), (3) and (4).

  6. HMG CoA reductase inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranylation of low-molecular-weight proteins in neonatal rat muscle cell culture.

    PubMed

    Flint, O P; Masters, B A; Gregg, R E; Durham, S K

    1997-07-01

    In previous studies, inhibition of cholesterol synthesis by HMG CoA reductase inhibitors (HMGRI) was associated with myotoxicity in cultures of neonatal rat skeletal myotubes, and rhabdomyolysis in rats, rabbits, and humans in vivo. In vitro myotoxicity was directly related to HMGRI-induced depletion of mevalonate, farnesol, and geranylgeraniol, since supplementation with these intermediate metabolites abrogated the toxicity. Both farnesol and geranylgeraniol are required for the posttranslational modification, or isoprenylation, of essential regulatory proteins in mammalian cells. The objective of the present study was to measure changes in protein isoprenylation in cultured neonatal rat skeletal muscle cells exposed for 24 hr to increasing concentrations of pravastatin or lovastatin. Proteins were labeled with [3H]mevalonate, [3H]farnesyl pyrophosphate (FPP), or [3H]geranylgeranyl pyrophosphate (GGPP), and then separated by SDS-PAGE and quantitated by scintillation counting and densitometry of autoradiographs. Mevalonate and FPP labeling of the majority of proteins increased in a concentration-dependent manner, even at concentrations greater than 2 microM lovastatin and 25 microM pravastatin that completely inhibited cholesterol synthesis. In contrast, mevalonate and FPP labeling of three protein bands with molecular weights of 26.6, 27.7, and 28.9 kDa was markedly inhibited at concentrations higher than 1 microM lovastatin and 400 microM pravastatin, which inhibited protein synthesis and disrupted myotube morphology after longer exposures in a previous study. In contrast, these proteins were equally well labeled by GGPP at all HMGRI concentrations tested, suggesting that isoprenylation of the 26.9-, 27.8-, and 28.9-kDa proteins requires geranylgeraniol. The results of this study indicate that HMGRI-induced myotoxicity is most likely related to reduced posttranslational modification of specific regulatory proteins by geranylgeraniol.

  7. The Molecular Weight Distribution of Polymer Samples

    ERIC Educational Resources Information Center

    Horta, Arturo; Pastoriza, M. Alejandra

    2007-01-01

    Various methods for the determination of the molecular weight distribution (MWD) of different polymer samples are presented. The study shows that the molecular weight averages and distribution of a polymerization completely depend on the characteristics of the reaction itself.

  8. Effect of molecular weight on polyphenylquinoxaline properties

    NASA Technical Reports Server (NTRS)

    Jensen, Brian J.

    1991-01-01

    A series of polyphenyl quinoxalines with different molecular weight and end-groups were prepared by varying monomer stoichiometry. Thus, 4,4'-oxydibenzil and 3,3'-diaminobenzidine were reacted in a 50/50 mixture of m-cresol and xylenes. Reaction concentration, temperature, and stir rate were studied and found to have an effect on polymer properties. Number and weight average molecular weights were determined and correlated well with viscosity data. Glass transition temperatures were determined and found to vary with molecular weight and end-groups. Mechanical properties of films from polymers with different molecular weights were essentially identical at room temperature but showed significant differences at 232 C. Diamine terminated polymers were found to be much less thermooxidatively stable than benzil terminated polymers when aged at 316 C even though dynamic thermogravimetric analysis revealed only slight differences. Lower molecular weight polymers exhibited better processability than higher molecular weight polymers.

  9. Production of high molecular weight polylactic acid

    DOEpatents

    Bonsignore, Patrick V.

    1995-01-01

    A degradable high molecular weight poly(lactic acid). A poly(lactic acid) has a terminal end group of one of carboxyl or hydroxyl groups with low molecular weight poly(lactic acid) units coupled with linking agents of di-isocyanates, bis-epoxides, bis-oxazolines and bis-ortho esters. The resulting high molecular weight poly(lactic acid) can be used for applications taking advantage of the improved physical properties.

  10. Production of high molecular weight polylactic acid

    DOEpatents

    Bonsignore, P.V.

    1995-11-28

    A degradable high molecular weight poly(lactic acid) is described. The poly(lactic acid) has a terminal end group of one of carboxyl or hydroxyl groups with low molecular weight poly(lactic acid) units coupled with linking agents of di-isocyanates, bis-epoxides, bis-oxazolines and bis-ortho esters. The resulting high molecular weight poly(lactic acid) can be used for applications taking advantage of the improved physical properties.

  11. Microdialysis unit for molecular weight separation

    DOEpatents

    Smith, Richard D.; Liu, Chuanliang

    1999-01-01

    The present invention relates generally to an apparatus and method for separating high molecular weight molecules from low molecular weight molecules. More specifically, the invention relates to the use of microdialysis for removal of the salt (low molecular weight molecules) from a nucleotide sample (high molecular weight molecules) for ESI-MS analysis. The dialysis or separation performance of the present invention is improved by (1) increasing dialysis temperature thereby increasing desalting efficiency and improving spectrum quality; (2) adding piperidine and imidazole to the dialysis buffer solution and reducing charge states and further increasing detection sensitivity for DNA; (3) using low concentrations (0-2.5 mM NH4OAc) of dialysis buffer and shifting the DNA negative ions to higher charge states, producing a nearly 10-fold increase in detection sensitivity and a slightly decreased desalting efficiency, or (4) any combination of (1), (2), and (3).

  12. Molecular characteristics of some commercial high-molecular-weight hyaluronans.

    PubMed

    Soltés, L; Mendichi, R; Lath, D; Mach, M; Bakos, D

    2002-10-01

    Commercially available hyaluronan (HA) samples were investigated by the method of size exclusion chromatography (SEC). The fractions eluted from the SEC column were on-line molecularly characterized by using a multi-angle laser light scattering (MALLS) photometer. Along with the SEC-MALLS technique, the high-molecular-weight HA biopolymers were (off-line) analyzed by capillary viscometry.

  13. Average molecular weight of surfactants in aerosols

    NASA Astrophysics Data System (ADS)

    Latif, M. T.; Brimblecombe, P.

    2007-09-01

    Surfactants in atmospheric aerosols determined as methylene blue active substances (MBAS) and ethyl violet active substances (EVAS). The MBAS and EVAS concentrations can be correlated with surface tension as determined by pendant drop analysis. The effect of surface tension was more clearly indicated in fine mode aerosol extracts. The concentration of MBAS and EVAS was determined before and after ultrafiltration analysis using AMICON centrifuge tubes that define a 5000 Da (5 K Da) nominal molecular weight fraction. Overall, MBAS and to a greater extent EVAS predominates in fraction with molecular weight below 5 K Da. In case of aerosols collected in Malaysia the higher molecular fractions tended to be a more predominant. The MBAS and EVAS are correlated with yellow to brown colours in aerosol extracts. Further experiments showed possible sources of surfactants (e.g. petrol soot, diesel soot) in atmospheric aerosols to yield material having molecular size below 5 K Da except for humic acid. The concentration of surfactants from these sources increased after ozone exposure and for humic acids it also general included smaller molecular weight surfactants.

  14. Biodegradation of high molecular weight polylactic acid

    NASA Astrophysics Data System (ADS)

    Stloukal, Petr; Koutny, Marek; Sedlarik, Vladimir; Kucharczyk, Pavel

    2012-07-01

    Polylactid acid seems to be an appropriate replacement of conventional non-biodegradable synthetic polymer primarily due to comparable mechanical, thermal and processing properties in its high molecular weight form. Biodegradation of high molecular PLA was studied in compost for various forms differing in their specific surface area. The material proved its good biodegradability under composting conditions and all investigated forms showed to be acceptable for industrial composting. Despite expectations, no significant differences in resulting mineralizations were observed for fiber, film and powder sample forms with different specific surface areas. The clearly faster biodegradation was detected only for the thin coating on porous material with high specific surface area.

  15. Biocompatible composites of ultrahigh molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Panin, S. V.; Kornienko, L. A.; Suan, T. Nguen; Ivanova, L. P.; Korchagin, M. A.; Chaikina, M. V.; Shilko, S. V.; Pleskachevskiy, Yu. M.

    2015-10-01

    Mechanical and tribotechnical characteristics of biocompatible, antifriction and extrudable composites based on ultrahigh molecular weight polyethylene (UHMWPE) as well as hybrid matrix "UHMWPE + PTFE" with biocompatible hydroxyapatite filler under the dry friction and boundary lubrication were investigated. A comparative analysis of effectiveness of adding the hydroxyapatite to improve the wear resistance of composites based on these two matrices was performed. It is shown that the wear intensity of nanocomposites based on the hybrid matrix is lower than that for the composites based on pure UHMWPE. Possibilities of using the composites of the polymer "UHMWPE-PTFE" mixture as a material for artificial joints implants are discussed.

  16. Low molecular weight melanoidins in coffee brew.

    PubMed

    Bekedam, E Koen; Roos, Ellen; Schols, Henk A; Van Boekel, Martinus A J S; Smit, Gerrit

    2008-06-11

    Analysis of low molecular weight (LMw) coffee brew melanoidins is challenging due to the presence of many non-melanoidin components that complicate analysis. This study focused on the isolation of LMw coffee brew melanoidins by separation of melanoidins from non-melanoidin components that are present in LMw coffee brew material. LMw coffee fractions differing in polarity were obtained by reversed-phase solid phase extraction and their melanoidin, sugar, nitrogen, caffeine, trigonelline, 5-caffeoylquinic acid, quinic acid, caffeic acid, and phenolic groups contents were determined. The sugar composition, the charge properties, and the absorbance at various wavelengths were investigated as well. The majority of the LMw melanoidins were found to have an apolar character, whereas most non-melanoidins have a polar character. The three isolated melanoidin-rich fractions represented 56% of the LMw coffee melanoidins and were free from non-melanoidin components. Spectroscopic analysis revealed that the melanoidins isolated showed similar features as high molecular weight coffee melanoidins. All three melanoidin fractions contained approximately 3% nitrogen, indicating the presence of incorporated amino acids or proteins. Surprisingly, glucose was the main sugar present in these melanoidins, and it was reasoned that sucrose is the most likely source for this glucose within the melanoidin structure. It was also found that LMw melanoidins exposed a negative charge, and this negative charge was inversely proportional to the apolar character of the melanoidins. Phenolic group levels as high as 47% were found, which could be explained by the incorporation of chlorogenic acids in these melanoidins.

  17. Polymer Molecular Weight Analysis by [Superscript 1]H NMR Spectroscopy

    ERIC Educational Resources Information Center

    Izunobi, Josephat U.; Higginbotham, Clement L.

    2011-01-01

    The measurement and analysis of molecular weight and molecular weight distribution remain matters of fundamental importance for the characterization and physical properties of polymers. Gel permeation chromatography (GPC) is the most routinely used method for the molecular weight determination of polymers whereas matrix-assisted laser…

  18. Molecular modeling of auxin transport inhibitors

    SciTech Connect

    Gardner, G.; Black-Schaefer, C.; Bures, M.G. )

    1990-05-01

    Molecular modeling techniques have been used to study the chemical and steric properties of auxin transport inhibitors. These bind to a specific site on the plant plasma membrane characterized by its affinity for N-1-naphthylphthalamic acid (NPA). A three-dimensional model was derived from critical features of ligands for the NPA receptor, and a suggested binding conformation is proposed. This model, along with three-dimensional structural searching techniques, was then used to search the Abbott corporate database of chemical structures. Of the 467 compounds that satisfied the search criteria, 77 representative molecules were evaluated for their ability to compete for ({sup 3}H)NPA binding to corn microsomal membranes. Nineteen showed activity that ranged from 16 to 85% of the maximum NPA binding. Four of the most active of these, from chemical classes not included in the original compound set, also inhibited polar auxin transport through corn coleoptile sections.

  19. Determinations of molecular weight and molecular weight distribution of high polymers by the rheological properties

    NASA Technical Reports Server (NTRS)

    Huang, J. Y.; Hou, T. H.; Tiwari, S. N.

    1989-01-01

    Several methods are reviewed by which the molecular weight (MW) and the molecular weight distribution (MWD) of polymeric material were determined from the rheological properties. A poly(arylene ether) polymer with six different molecular weights was used in this investigation. Experimentally measured MW and MWD were conducted by GPC/LALLS (gel permeation chromatography/low angle laser light scattering), and the rheological properties of the melts were measured by a Rheometric System Four rheometer. It was found that qualitative information of the MW and MWD of these polymers could be derived from the viscoelastic properties, with the methods proposed by Zeichner and Patel, and by Dormier et al., by shifting the master curves of the dynamic storage modulus, G', and the loss modulus, G'', along the frequency axis. Efforts were also made to calculate quantitative profiles of MW and MWD for these polymers from their rheological properties. The technique recently proposed by Wu was evaluated. It was found that satisfactory results could only be obtained for polymers with single modal distribution in the molecular weight.

  20. Unexpected molecular weight effect in polymer nanocomposites

    SciTech Connect

    Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; Fan, Fei; Bocharova, Vera; Martin, Halie J.; Etampawala, Thusitha N.; White, Benjamin Tyler; Saito, Tomonori; Kang, Nam -Goo; Dadmun, Mark D.; Mays, Jimmy W.; Sokolov, Alexei P.

    2016-01-22

    Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal a reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.

  1. Unexpected molecular weight effect in polymer nanocomposites

    DOE PAGES

    Cheng, Shiwang; Holt, Adam P.; Wang, Huiqun; ...

    2016-01-22

    Here, the properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp constrast to theoretical predictions. Further analyses reveal amore » reduction in mass density of the interfacial layer with increasing MW, which can explain these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties.« less

  2. Rubber molecular weight regulation, in vitro, in plant species that produce high and low molecular weights in vivo.

    PubMed

    Cornish, K; Castillón, J; Scott, D J

    2000-01-01

    In three rubber-producing species, in vitro, the rates of initiation and polymerization and the biopolymer molecular weight produced were affected by the concentration of farnesyl diphosphate (FPP) initiator and isopentenyl diphosphate (IPP) elongation substrate (monomer). Ficus elastica, a low molecular weight-producer in vivo, synthesized rubber polymers approximately twice the molecular weight of those made by Hevea brasiliensis or Parthenium argentatum (which produce high molecular weights in vivo), possibly due to its lower IPP Km. In all species, increasing FPP concentrations increased rubber biosynthetic rate and new molecules initiated but decreased molecular weight by competition with the allylic diphosphate (APP) end of elongating rubber molecules for the APP binding site. Increasing IPP concentrations increased rubber biosynthetic rate and rubber molecular weight, but only when FPP concentrations were below the FPP Km's or where negative cooperativity operated. In conclusion, rubber transferase is not the prime regulator of rubber molecular weight in vivo.

  3. The Molecular Weight Distribution of Polymer Samples

    NASA Astrophysics Data System (ADS)

    Horta, Arturo; Pastoriza, M. Alejandra

    2007-07-01

    Introductory polymer courses and textbooks discuss the statistical distribution of chain lengths or molecular weight that exists in polymers and connect the averages and breadth of such distribution with the mechanism of the polymerization, for example, with the degree of advancement or stoichiometry in step-growth polymerization or with the existence of transferences or with the type of termination in chain addition polymerization. To determine averages and breadth of the distribution, the polymer has to be separated from the reaction medium and converted into a "sample". In this process, the shorter chains, which are most soluble, may be lost with the result that the sample is not identical to the original polymer. A student exercise is proposed and developed, in which we calculate the difference between "sample" and original polymer. We use standard material given in the introductory courses or textbooks such that the calculation can be performed easily by the students. The results are discussed to ascertain whether the different distribution of the sample may alter the interpretation of the mechanism by which the original polymer was obtained.

  4. High molecular weight melanoidins from coffee brew.

    PubMed

    Bekedam, E Koen; Schols, Henk A; van Boekel, Martinus A J S; Smit, Gerrit

    2006-10-04

    The composition of high molecular weight (HMw) coffee melanoidin populations, obtained after ethanol precipitation, was studied. The specific extinction coefficient (K(mix)) at 280, 325, 405 nm, sugar composition, phenolic group content, nitrogen content, amino acid composition, and non-protein nitrogen (NPN) content were investigated. Results show that most HMw coffee melanoidins are soluble at high ethanol concentrations. The amino acid composition of the HMw fractions was similar, while 17% (w/w) of the nitrogen was NPN, probably originating from degraded amino acids/proteins and now part of melanoidins. A strong correlation between the melanoidin content, the NPN, and protein content was found. It was concluded that proteins are incorporated into the melanoidins and that the degree of chemical modification, for example, by phenolic groups, determines the solubility of melanoidins in ethanol. Although the existence of covalent interaction between melanoidins and polysaccharides were not proven in this study, the findings suggest that especially arabinogalactan is likely involved in melanoidin formation. Finally, phenolic groups were present in the HMw fraction of coffee, and a correlation was found with the melanoidin concentration.

  5. Low molecular weight heparins and heparinoids.

    PubMed

    Eikelboom, John W; Hankey, Graeme J

    2002-10-07

    Several low molecular weight (LMW) heparin preparations, including dalteparin, enoxaparin and nadroparin, as well as the heparinoid danaparoid sodium, are approved for use in Australia. LMW heparins are replacing unfractionated heparin for the prevention and treatment of venous thromboembolism and the treatment of non-ST-segment-elevation acute coronary syndromes. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and predictable anticoagulant response (avoiding the need for dose adjustment or laboratory monitoring in most patients), and a low risk of heparin-induced thrombocytopenia and osteoporosis. Laboratory monitoring of LMW heparin therapy should be considered in newborns and children, patients with renal impairment, those who are pregnant, and those at the extremes of bodyweight (eg, < 40 kg or > 100 kg). LMW heparins should: be avoided or used with caution in patients undergoing neuraxial anaesthesia, owing to the potential for epidural haematoma formation; not be used (ie, are contraindicated) in patients with immune heparin-induced thrombocytopenia, as they may cross-react with anti-heparin antibodies. Conventional unfractionated heparin retains a role in the management of patients at high risk of bleeding, undergoing invasive procedures, and patients with renal failure owing to its shorter half-life, reversibility with protamine sulfate, and extrarenal metabolism. The heparinoid danaparoid sodium is effective for the treatment of heparin-induced thrombocytopenia.

  6. Molecular Weight Effects on the Viscoelastic Response of a Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2000-01-01

    The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC -SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of each material with different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have increased creep compliance and creep compliance rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of approximately 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly.

  7. Molecular weight of aquatic fulvic acids by vapor pressure osmometry

    USGS Publications Warehouse

    Aiken, G.R.; Malcolm, R.L.

    1987-01-01

    The molecular weights of aquatic fulvic acids extracted from five rivers were determined by vapor pressure osmometry with water and tetrahydrofuran as solvents. The values obtained ranged from 500 to 950 dallons, indicating that the molecular weights of aquatic fulvic acids are not as great as has been suggested in some other molecular weight studies. The samples were shown to be relatively monodisperse from radii of gyration measurements determined by small angle x-ray scattering. THF affords greater precision and accuracy than H2O in VPO measurements, and was found to be a suitable solvent for the determination of molecular weight of aquatic fulvic acid because it obviates the dissociation problem. An inverse correlation was observed with these samples between the concentration of Ca++ and Mg++ in the river water and the radii of gyration and molecular weights of the corresponding fulvic acid samples. ?? 1987.

  8. Evaluation of ultrafiltration for determining molecular weight of fulvic acid

    USGS Publications Warehouse

    Aiken, G.R.

    1984-01-01

    Two commonly used ultrafiltration membranes are evaluated for the determination of molecular weights of humic substances. Polyacrylic acids of Mr 2000 and 5000 and two well-characterized fulvic acids are used as standards. Molecular size characteristics of standards, as determined by small-angle X-ray scattering, are presented. Great care in evaluating molecular weight data obtained by ultrafiltration is needed because of broad nominal cutoffs and membrane-solute interactions.

  9. Molecular Factors Governing the Liquid and Glassy States Recrystallization of Celecoxib in Binary Mixtures with Excipients of Different Molecular Weights.

    PubMed

    Grzybowska, K; Chmiel, K; Knapik-Kowalczuk, J; Grzybowski, A; Jurkiewicz, K; Paluch, M

    2017-03-08

    Transformation of poorly water-soluble crystalline pharmaceuticals to the amorphous form is one of the most promising strategies to improve their oral bioavailability. Unfortunately, the amorphous drugs are usually thermodynamically unstable and may quickly return to their crystalline form. A very promising way to enhance the physical stability of amorphous drugs is to prepare amorphous compositions of APIs with certain excipients which can be characterized by significantly different molecular weights, such as polymers, acetate saccharides, and other APIs. By using different experimental techniques (broadband dielectric spectroscopy, differential scanning calorimetry, X-ray diffraction) we compare the effect of adding the large molecular weight polymer-polyvinylpyrrolidone (PVP K30)-and the small molecular weight excipient-octaacetylmaltose (acMAL)-on molecular dynamics as well as the tendency to recrystallization of the amorphous celecoxib (CEL) in the amorphous solid dispersions: CEL-PVP and CEL-acMAL. The physical stability investigations of the binary systems were performed in both the supercooled liquid and glassy states. We found that acMAL is a better inhibitor of recrystallization of amorphous CEL than PVP K30 deep in the glassy state (T < Tg). In contrast, PVP K30 is a better crystallization inhibitor of CEL than acMAL in the supercooled liquid state (at T > Tg). We discuss molecular factors governing the recrystallization of amorphous CEL in examined solid dispersions.

  10. Low molecular weight species in humic and fulvic fractions

    USGS Publications Warehouse

    Wilson, M.A.; Collin, P.J.; Malcolm, R.L.; Perdue, E.M.; Cresswell, P.

    1988-01-01

    Fourier transform solution 1H nuclear magnetic resonance (NMR) spectrometry with homogated water peak irradiation is a useful method for detecting low molecular weight substances in humic extracts. Succinate, acetate, methanol, formate, lactate and some aryl methoxyl compounds have been detected in extracts from a wide range of sources. In view of the controversy over whether low molecular weight substances are contaminants in humic extracts introduced by the concentration procedure, we report that some of these materials are not contaminants since 1H-NMR can be used to follow their formation from higher molecular weight species. ?? 1988.

  11. Free volume variation with molecular weight of polymers

    NASA Technical Reports Server (NTRS)

    Singh, Jag J.; Eftekhari, Abe; Hinkley, Jeffrey A.; St.clair, Terry L.; Jensen, Brian J.

    1992-01-01

    Free volume measurements were made in several molecular weight fractions of two different geometries of poly(arylene ether ketone)s. Free volumes were measured using positron lifetime spectroscopy. It has been observed that the free volume cell size V(sub f) varies with the molecular weight M of the test samples according to an equation of the form V(sub f) = AM(B), where A and B are constants. The molecular weights computed from the free volume cell sizes are in good agreement with the values measured by gel permeation chromatography.

  12. Free volume model for molecular weights of polymers

    NASA Technical Reports Server (NTRS)

    Singh, J. J.; Eftekhari, A.

    1992-01-01

    A free volume model has been developed for determining molecular weights of linear polymers. It is based on the size of free volume cells in two geometries of poly(arylene ether ketone)s. Free volume cell sizes in test samples were measured using positron lifetime spectroscopy. The molecular weights computed from free volume cell sizes are in good agreement with the values measured by gel permeation chromatography, with a low angle laser light scattering photometer as the detector. The model has been further tested on two atactic polystyrene samples, where it predicted the ratio of their molecular weights with reasonable accuracy.

  13. Do Low Molecular Weight Agents Cause More Severe Asthma than High Molecular Weight Agents?

    PubMed Central

    Meca, Olga; Cruz, María-Jesús; Sánchez-Ortiz, Mónica; González-Barcala, Francisco-Javier; Ojanguren, Iñigo; Munoz, Xavier

    2016-01-01

    Introduction The aim of this study was to analyse whether patients with occupational asthma (OA) caused by low molecular weight (LMW) agents differed from patients with OA caused by high molecular weight (HMW) with regard to risk factors, asthma presentation and severity, and response to various diagnostic tests. Methods Seventy-eight patients with OA diagnosed by positive specific inhalation challenge (SIC) were included. Anthropometric characteristics, atopic status, occupation, latency periods, asthma severity according to the Global Initiative for Asthma (GINA) control classification, lung function tests and SIC results were analysed. Results OA was induced by an HMW agent in 23 patients (29%) and by an LMW agent in 55 (71%). A logistic regression analysis confirmed that patients with OA caused by LMW agents had a significantly higher risk of severity according to the GINA classification after adjusting for potential confounders (OR = 3.579, 95% CI 1.136–11.280; p = 0.029). During the SIC, most patients with OA caused by HMW agents presented an early reaction (82%), while in patients with OA caused by LMW agents the response was mainly late (73%) (p = 0.0001). Similarly, patients with OA caused by LMW agents experienced a greater degree of bronchial hyperresponsiveness, measured as the difference in the methacholine dose-response ratio (DRR) before and after SIC (1.77, range 0–16), compared with patients with OA caused by HMW agents (0.87, range 0–72), (p = 0.024). Conclusions OA caused by LMW agents may be more severe than that caused by HMW agents. The severity of the condition may be determined by the different mechanisms of action of these agents. PMID:27280473

  14. Low-molecular weight plasma proteome analysis using centrifugal ultrafiltration.

    PubMed

    Greening, David W; Simpson, Richard J

    2011-01-01

    The low-molecular weight fraction (LMF) of the human plasma proteome is an invaluable source of biological information, especially in the context of identifying plasma-based biomarkers of disease. This protocol outlines a standardized procedure for the rapid/reproducible LMF profiling of human plasma samples using centrifugal ultrafiltration fractionation, followed by 1D-SDS-PAGE separation and nano-LC-MS/MS. Ultrafiltration is a convective process that uses anisotropic semipermeable membranes to separate macromolecular species on the basis of size. We have optimized centrifugal ultrafiltration for plasma fractionation with respect to buffer and solvent composition, centrifugal force, duration and temperature to facilitate >95% recovery, and enrichment of low-M (r) components from human plasma. Using this protocol, >260 unique peptides can be identified from a single plasma profiling experiment using 100 μL of plasma (Greening and Simpson, J Proteomics 73:637-648, 2010). The efficacy of this method is demonstrated by the identification, for the first time, of several plasma proteins (e.g., protein KIAA0649 (Q9Y4D3), rheumatoid factor D5, serine protease inhibitor A3, and transmembrane adapter protein PAG) previously not reported in extant high-confidence Human Proteome Organization Plasma Proteome Project datasets.

  15. Molecular Dynamic Screening Sesquiterpenoid Pogostemon Herba as Suggested Cyclooxygenase Inhibitor

    PubMed Central

    Raharjo, Sentot Joko; Kikuchi, Takeshi

    2016-01-01

    Objective: Virtual molecular dynamic sesquiterpenoid Pogostemon Herba (CID56928117, CID94275, CID107152, and CID519743) have screening as cyclooxygenase (COX-1/COX-2) selective inhibitor. Methods: Molecular interaction studies sesquiterpenoid compounds with COX-1 and COX-2 were using the molecular docking tools by Hex 8.0 and interactions were further visualized using by Discovery Studio Client 3.5 software tool and Virtual Molecular Dynamic 1.9.1 software. The binding energy calculation of molecular dynamic interaction was calculated by AMBER12 software. Result: The analysis of the sesquiterpenoid compounds showed that CID56928117, CID94275, CID107152, and CID519743 have suggested as inhibitor of COX-1 and COX-2. Conclusion: Collectively, the scoring binding energy calculation (with PBSA Model Solvent) sesquiterpenoid compounds: CID519743 had suggested as candidate for non-selective inhibitor; CID56928117 and CID94275 had suggested as candidate for a selective COX-1 inhibitor; and CID107152 had suggested as candidate for a selective COX-2 inhibitor. PMID:28077888

  16. A simplified electrophoretic system for determining molecular weights of proteins.

    PubMed

    Manwell, C

    1977-09-01

    Electrophoresis of 31 different proteins in commercially prepared polyacrylamide gradient gels, Gradipore, yields a linear relationship between a hypothetical limiting pore size (the reciprocal of a limiting gel concentration, GL) and the cube root of the mol.wt., over the range 13 500-9000 000. A regression analysis of these data reveals that 98.6% of all variability in 1/GL is explained by the molecular weight, and this degree of accuracy compares favourably with existing methods for the determination of molecular weight by retardation of mobility in polyacrylamide. This new procedure has the additional advantages that molecular-weight standards can be obtained from readily available body fluids or tissue extracts by localizing enzymes and other proteins by standard histochemical methods, and that the same electrophoretic system can be used in determining molecular weights as is used in routine surveys of populations for individual and species variation in protein heterogeneity.

  17. Low molecular weight salts combined with fluorinated solvents for electrolytes

    DOEpatents

    Tikhonov, Konstantin; Yip, Ka Ki; Lin, Tzu-Yuan; Lei, Norman; Guerrero-Zavala, Guillermo; Kwong, Kristie W.

    2015-11-10

    Provided are electrochemical cells and electrolytes used to build such cells. An electrolyte includes at least one salt having a molecular weight less than about 250. Such salts allow forming electrolytes with higher salt concentrations and ensure high conductivity and ion transport in these electrolytes. The low molecular weight salt may have a concentration of at least about 0.5M and may be combined with one or more other salts, such as linear and cyclic imide salts and/or methide salts. The concentration of these additional salts may be less than that of the low molecular weight salt, in some embodiments, twice less. The additional salts may have a molecular weight greater than about 250. The electrolyte may also include one or more fluorinated solvents and may be capable of maintaining single phase solutions at between about -30.degree. C. to about 80.degree. C.

  18. Molecular-Weight-Controlled, End-Capped Polybenzimidazoles

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Hergenrother, Paul M.; Smith, Joseph G., Jr.

    1993-01-01

    Novel molecular-weight-controlled end-capped poly(arylene ether benzimidazole)s (PAEBI's) prepared by nucleophilic displacement reaction of di(hydroxyl)benzimidazole monomers with activated aromatic dihalides. Polymers prepared at various molecular weights by upsetting stoichiometry of monomers and end-capped with monohydroxybenzimidazole. Exhibit favorable physical and mechanical properties, improved solubility in polar aprotic solvents and better compression moldability. Potential applications as adhesives, coatings, films, fibers, membranes, moldings, and composite matrix resins.

  19. Identification of the high molecular weight isoform of phostensin.

    PubMed

    Lin, Yu-Shan; Huang, Hsien-Lu; Liu, Wei-Ting; Lin, Ta-Hsien; Huang, Hsien-Bin

    2014-01-15

    Phostensin is encoded by KIAA1949. 5'-RACEanalysis has been used to identify the translation start site of phostensin mRNA, indicating that it encodes 165 amino acids with an apparent molecular weight of 26 kDa on SDS-PAGE. This low-molecular-weight phostensin is present in human peripheral blood mononuclear cells and many leukemic cell lines. Phostensin is a protein phosphatase-1(PP1) binding protein. It also contains one actin-binding motif at its C-terminal region and binds to the pointed ends of actin filaments, modulating actin dynamics. In the current study, a high-molecular-weight phostensin is identified by using immunoprecipitationin combination with a proteomic approach. This new species of phostensin is also encoded by KIAA1949 and consists of 613 amino acids with an apparent molecular weight of 110 kDa on SDS-PAGE. The low-molecular-weight and high-molecular-weight phostensins were named as phostensin-α and phostensin-β, respectively. Although phostensin-α is the C-terminal region of phostensin-β, it is not degraded from phostensin-β. Phostensin-β is capable of associating with PP1 and actin filaments, and is present in many cell lines.

  20. Evaluation of a Viscosity-Molecular Weight Relationship.

    ERIC Educational Resources Information Center

    Mathias, Lon J.

    1983-01-01

    Background information, procedures, and results are provided for a series of graduate/undergraduate polymer experiments. These include synthesis of poly(methylmethacrylate), viscosity experiment (indicating large effect even small amounts of a polymer may have on solution properties), and measurement of weight-average molecular weight by light…

  1. Microbial detection with low molecular weight RNA

    NASA Technical Reports Server (NTRS)

    Kourentzi, K. D.; Fox, G. E.; Willson, R. C.

    2001-01-01

    The need to monitor microorganisms in the environment has increased interest in assays based on hybridization probes that target nucleic acids (e.g., rRNA). We report the development of liquid-phase assays for specific bacterial 5S rRNA sequences or similarly sized artificial RNAs (aRNAs) using molecular beacon technology. These beacons fluoresce only in the presence of specific target sequences, rendering as much as a 27-fold fluorescence enhancement. The assays can be used with both crude cell lysates and purified total RNA preparations. Minimal sample preparation (e.g., heating to promote leakage from cells) is sufficient to detect many Gram-negative bacteria. Using this approach it was possible to detect an aRNA-labeled Escherichia coli strain in the presence of a large background of an otherwise identical E. coli strain. Finally, by using a longer wavelength carboxytetramethylrhodamine beacon it was possible to reduce the fraction of the signal due to cellular autofluorescence to below 0.5%.

  2. Molecular weight, polydispersity, and spectroscopic properties of aquatic humic substances

    USGS Publications Warehouse

    Chin, Y.-P.; Aiken, G.; O'Loughlin, E.

    1994-01-01

    The number- and weight-averaged molecular weights of a number of aquatic fulvic acids, a commercial humic acid, and unfractionated organic matter from four natural water samples were measured by high-pressure size exclusion chromatography (HPSEC). Molecular weights determined in this manner compared favorably with those values reported in the literature. Both recent literature values and our data indicate that these substances are smaller and less polydisperse than previously believed. Moreover, the molecular weights of the organic matter from three of the four natural water samples compared favorably to the fulvic acid samples extracted from similar environments. Bulk spectroscopic properties of the fulvic substances such as molar absorptivity at 280 nm and the E4/E6 ratio were also measured. A strong correlation was observed between molar absorptivity, total aromaticity, and the weight average molecular weights of all the humic substances. This observation suggests that bulk spectroscopic properties can be used to quickly estimate the size of humic substances and their aromatic contents. Both parameters are important with respect to understanding humic substance mobility and their propensity to react with both organic and inorganic pollutants. ?? 1994 American Chemical Society.

  3. Endogenous ethanol affects biopolyester molecular weight in recombinant Escherichia coli.

    PubMed

    Hiroe, Ayaka; Hyakutake, Manami; Thomson, Nicholas M; Sivaniah, Easan; Tsuge, Takeharu

    2013-11-15

    In biopolyester synthesis, polyhydroxyalkanoate (PHA) synthase (PhaC) catalyzes the polymerization of PHA in bacterial cells, followed by a chain transfer (CT) reaction in which the PHA polymer chain is transferred from PhaC to a CT agent. Accordingly, the frequency of CT reaction determines PHA molecular weight. Previous studies have shown that exogenous alcohols are effective CT agents. This study aimed to clarify the effect of endogenous ethanol as a CT agent for poly[(R)-3-hydroxybutyrate] [P(3HB)] synthesis in recombinant Escherichia coli, by comparing with that of exogenous ethanol. Ethanol supplementation to the culture medium reduced P(3HB) molecular weights by up to 56% due to ethanol-induced CT reaction. NMR analysis of P(3HB) polymers purified from the culture supplemented with (13)C-labeled ethanol showed the formation of a covalent bond between ethanol and P(3HB) chain at the carboxyl end. Cultivation without ethanol supplementation resulted in the reduction of P(3HB) molecular weight with increasing host-produced ethanol depending on culture aeration. On the other hand, production in recombinant BW25113(ΔadhE), an alcohol dehydrogenase deletion strain, resulted in a 77% increase in molecular weight. Analysis of five E. coli strains revealed that the estimated number of CT reactions was correlated with ethanol production. These results demonstrate that host-produced ethanol acts as an equally effective CT agent as exogenous ethanol, and the control of ethanol production is important to regulate the PHA molecular weight.

  4. Are molecular weights of proteins determined by superose 12 column chromatography correct?

    PubMed

    Lee, Shih-Chieh; Whitaker, John R

    2004-08-11

    Our research on several proteins indicates that accurate molecular weights cannot be determined by Superose 12 column chromatography. In support of this statement, we present data on molecular weights of purified red kidney bean alpha-amylase inhibitor (RKB alphaAI) and white kidney bean alpha-amylase inhibitor (WKB alphaAI) to document this problem. The molecular weight of purified RKB alphaAI determined by Sephadex G-100 gel filtration, polyacrylamide gel electrophoresis, Superose 12 gel filtration and cDNA were 49.0, 51.0, 22.9, and 49.805 kDa (not glycosylated), respectively. The molecular weights of WKB alphaAI by several methods were as follows: Sephadex G-100 gel filtration, 51.0 kDa; Superose 12 gel filtration in 0.2 M NaCl buffer, 23.1 kDa; polyacrylamide gel electrophoresis (PAGE), 51.0 kDa; sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), 45.0 kDa; multiangle laser light scattering (MALLS), 49.940 kDa; laser-assisted time-of-flight mass spectrometry (LATOFMS), 56.714 kDa; and cDNA sequence (with 12.2% carbohydrate), 55.9 kDa. The data indicate there is ionic interaction between proteins and the matrix of Superose 12 in low ionic strength buffers and hydrophobic interaction at higher ionic strength buffers. Researchers should be cautious when using Superose 12 columns for molecular weight determinations.

  5. High molecular weight polyglycerol-based multivalent mannose conjugates.

    PubMed

    Kizhakkedathu, Jayachandran N; Creagh, A Louise; Shenoi, Rajesh A; Rossi, Nicholas A A; Brooks, Donald E; Chan, Timmy; Lam, Jonathan; Dandepally, Srinivasa R; Haynes, Charles A

    2010-10-11

    We report the synthesis and characterization of multivalent mannose conjugates based on high molecular weight hyperbranched polyglycerols (HPG). A range of glycoconjugates were synthesized from high molecular weight HPGs (up to 493 kDa) and varying mannose units (22-303 per HPG). Hemagglutination assays using fresh human red blood cells and concanavalin A (Con A) showed that HPG-mannose conjugates exhibited a large enhancement in the relative potency of conjugates (as high as 40000) along with a significant increment in relative activity per sugar (up to 255). The size of the HPG scaffold and the number of mannose residues per HPG were all shown to influence the enhancement of binding interactions with Con A. Isothermal titration calorimetry (ITC) experiments confirmed the enhanced binding affinity and showed that both molecular size and ligand density play important roles. The enhancement in Con A binding to the high molecular weight HPG-mannose conjugates is due to a combination of inter- and intramolecular mannose binding. A few fold increments in the binding constant were obtained over mannose upon covalent attachment to HPG. The binding enhancement is due to the highly favorable entropic contribution to the multiple interactions of Con A to mannose residues on HPG. The high molecular weight HPG-mannose conjugates showed positive cooperativity in binding to Con A. Although carbohydrate density has less of an effect on functional valency of the conjugate compared to the molecular size, it determines the binding affinity.

  6. Inhibition of protein-protein interactions with low molecular weight compounds

    PubMed Central

    Matthews, Marilyn M.; Weber, David J.; Shapiro, Paul S.; Coop, Andrew; MacKerell, Alexander D.

    2010-01-01

    An overview of issues associated with the design and development of low molecular weight inhibitors of protein-protein interactions is presented. Areas discussed include information on the nature of protein-protein interfaces, methods to characterize those interfaces and methods by which that information is applied towards ligand identification and design. Specific examples of the strategy for the identification of inhibitors of protein-protein interactions involving the proteins p56lck kinase, ERK2 and the calcium-binding protein S100B are presented. Physical characterization of the inhibitors identified in those studies shows them to have drug-like and lead-like properties, indicating their potential to be developed into therapeutic agents. PMID:21927717

  7. [Low molecular weight heparins. Implications in anesthesia and resuscitation].

    PubMed

    Llau, J V; Hoyas, L; Ezpeleta, J; García-Polit, J; Barberá, M; Santes, M J

    1997-02-01

    Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).

  8. In vitro biological evaluation of high molecular weight hyperbranched polyglycerols.

    PubMed

    Kainthan, Rajesh Kumar; Hester, Samuel R; Levin, Elena; Devine, Dana V; Brooks, Donald Elliott

    2007-11-01

    Low molecular weight hyperbranched polyglycerols are highly water soluble and biocompatible polyether polyols, which can be synthesized in a controlled manner with narrow polydispersity. Recently we reported the synthesis and characterization of very high molecular weight (Mn up to 700,000) and narrowly polydispersed polyglycerols which could be potentially used as alternatives to high generation dendrimers which are difficult to make. A detailed biocompatibility testing of these polymers conducted in vitro is reported here. The in vitro studies include hemocompatibility testing for effects on coagulation (prothrombin time (PT), activated partial thromboplastin time (APTT), plasma recalcification time (PRT), thrombelastograph parameters (TEG)), complement activation, platelet activation, red blood cell aggregation and cytotoxicity. Results from these studies show that these high molecular weight polyglycerols are highly biocompatible and are potential candidates for various applications in nanobiotechnology and in nanomedicine. Moreover these polymers are thermally and oxidatively stable.

  9. Rheological investigation of highly filled polymers: Effect of molecular weight

    NASA Astrophysics Data System (ADS)

    Hnatkova, Eva; Hausnerova, Berenika; Hales, Andrew; Jiranek, Lukas; Vera, Juan Miguel Alcon

    2015-04-01

    The paper deals with rheological properties of highly filled polymers used in powder injection molding. Within the experimental framework seven PIM feedstocks based on superalloy Inconel 718 powder were prepared. Each feedstock contains the fixed amount of powder loading and the same composition of binder system consisting of three components: polyethylene glycol (PEG) differing in molecular weight, poly (methyl methacrylate) (PMMA) and stearic acid (SA). The aim is to investigate the influence of PEG's molecular weight on the flow properties of feedstocks. Non-Newtonian indices, representing the shear rate sensitivity of the feedstocks, are obtained from a polynomial fit, and found to vary within measured shear rates range from 0.2 to 0.8. Temperature effect is considered via activation energies, showing decreasing trend with increasing of molecular weight of PEG (except of feedstock containing 1,500 g.mol-1 PEG).

  10. Synthesis of High Molecular Weight Para-Phenylene PBI

    DTIC Science & Technology

    1974-11-01

    give high molecular weight m-phenylene PBI (Reference 7). The polymer was completely soluble in methanesulfonic acid and 98% formic acid . Polymer with...mono- mer is a white crystalline solid which can be quantitatively hydrolized in an acid medium to give the free TAB. Stoichiometric quantities of IX...WEIGHT "PARA"-PHENYLENE PBI TECHNICAL REPORT AFML-TR-74-199 NOVEMBER 1974 Distribution limited to U.S.Government agencies only, test and evaluation

  11. Influence of molecular weight and degree of deacetylation of low molecular weight chitosan on the bioactivity of oral insulin preparations.

    PubMed

    Qinna, Nidal A; Karwi, Qutuba G; Al-Jbour, Nawzat; Al-Remawi, Mayyas A; Alhussainy, Tawfiq M; Al-So'ud, Khaldoun A; Al Omari, Mahmoud M H; Badwan, Adnan A

    2015-03-27

    The objective of the present study was to prepare and characterize low molecular weight chitosan (LMWC) with different molecular weight and degrees of deacetylation (DDA) and to optimize their use in oral insulin nano delivery systems. Water in oil nanosized systems containing LMWC-insulin polyelectrolyte complexes were constructed and their ability to reduce blood glucose was assessed in vivo on diabetic rats. Upon acid depolymerization and testing by viscosity method, three molecular weights of LMWC namely, 1.3, 13 and 18 kDa were obtained. As for the DDA, three LMWCs of 55%, 80% and 100% DDA were prepared and characterized by spectroscopic methods for each molecular weight. The obtained LMWCs showed different morphological and in silico patterns. Following complexation of LMWCs with insulin, different aggregation sizes were obtained. Moreover, the in vivo tested formulations showed different activities of blood glucose reduction. The highest glucose reduction was achieved with 1.3 kDa LMWC of 55% DDA. The current study emphasizes the importance of optimizing the molecular weight along with the DDA of the incorporated LMWC in oral insulin delivery preparations in order to ensure the highest performance of such delivery systems.

  12. RHEOLOGICAL PROPERTIES & MOLECULAR WEIGHT DISTRIBUTIONS OF FOUR PERFLUORINATED THERMOPLASTIC POLYMERS

    SciTech Connect

    Hoffman, D M; Shields, A L

    2009-02-24

    Dynamic viscosity measurements and molecular weight estimates have been made on four commercial, amorphous fluoropolymers with glass transitions (Tg) above 100 C: Teflon AF 1600, Hyflon AD 60, Cytop A and Cytop M. These polymers are of interest as binders for the insensitive high explosive 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) because of their high density and Tg above ambient, but within a suitable processing range of TATB. As part of this effort, the rheological properties and molecular weight distributions of these polymers were evaluated.

  13. Mean molecular weight and hydrogen abundance of Titan's atmosphere

    NASA Technical Reports Server (NTRS)

    Samuelson, R. E.; Hanel, R. A.; Kunde, V. G.; Maguire, W. C.

    1981-01-01

    The 200-600/cm continuum opacity in the troposphere and lower stratosphere of Titan is inferred from thermal emission spectra from the Voyager 1 IR spectrometer (IRIS). The surface temperature and mean molecular weight are between 94 and 97 K and between 28.3 and 29.2 AMU, respectively. The mole fraction of molecular hydrogen is 0.002 + or - 0.001, which is equivalent to an abundance of approximately 0.2 + or - 0.1 km amagat.

  14. Preparation of soybean oil polymers with high molecular weight

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cationic polymerization of soybean oils was initiated by boron trifluoride diethyl etherate BF3.O(C2H5)2 in supercritical carbon dioxide (scCO2) medium. The resulting polymers had molecular weight ranging from 21,842 to 118,300 g/mol. Nuclear magnetic resonance spectroscopy (NMR) and gel perme...

  15. Low-molecular-weight heparins in patients with atrial fibrillation.

    PubMed

    Calvo Romero, J M

    2016-10-27

    In clinical practice, low-molecular-weight heparins are used relatively frequently in patients with atrial fibrillation to prevent embolic events. In this article, it is revised the available evidence in the following clinical situations: rapid onset of anticoagulation, bridging therapy (replacing long-term oral anticoagulant therapy around an invasive procedure) and transesophageal echocardiography-guided cardioversion.

  16. A Pan-GTPase Inhibitor as a Molecular Probe.

    PubMed

    Hong, Lin; Guo, Yuna; BasuRay, Soumik; Agola, Jacob O; Romero, Elsa; Simpson, Denise S; Schroeder, Chad E; Simons, Peter; Waller, Anna; Garcia, Matthew; Carter, Mark; Ursu, Oleg; Gouveia, Kristine; Golden, Jennifer E; Aubé, Jeffrey; Wandinger-Ness, Angela; Sklar, Larry A

    2015-01-01

    Overactive GTPases have often been linked to human diseases. The available inhibitors are limited and have not progressed far in clinical trials. We report here a first-in-class small molecule pan-GTPase inhibitor discovered from a high throughput screening campaign. The compound CID1067700 inhibits multiple GTPases in biochemical, cellular protein and protein interaction, as well as cellular functional assays. In the biochemical and protein interaction assays, representative GTPases from Rho, Ras, and Rab, the three most generic subfamilies of the GTPases, were probed, while in the functional assays, physiological processes regulated by each of the three subfamilies of the GTPases were examined. The chemical functionalities essential for the activity of the compound were identified through structural derivatization. The compound is validated as a useful molecular probe upon which GTPase-targeting inhibitors with drug potentials might be developed.

  17. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

    PubMed Central

    Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  18. Molecular recognition between pancreatic lipase and natural and synthetic inhibitors.

    PubMed

    Bello, Martiniano; Basilio-Antonio, Lucia; Fragoso-Vázquez, Jonathan; Avalos-Soriano, Anaguiven; Correa-Basurto, José

    2017-05-01

    Pancreatic lipase (PL) is a primary lipase critical for triacylglyceride digestion in humans and is considered as a promising target for the treatment of obesity. Although the current synthetic drugs available for treating obesity have been demonstrated to be effective in inhibiting PL, their prolonged usage results in severe side effects. Based on this argument, in this study, we evaluated the structural and energetic features linked to molecular recognition between two well-known PL inhibitors, orlistat (ORL, synthetic inhibitor) and (-)-epigallocatechin gallate (EGCG, natural inhibitor) and PL through molecular dynamics simulations and free energy calculations of ORL and EGCG at the PL binding site when it is isolated (PL) from the heterodimer complex, forming the heterodimer complex with colipase (PLCL) and lacking structural calcium. Our study showed that the binding free energy of ORL and EGCG to the target correlates with their experimental affinity tendency. The presence of the heterodimer PLCL state, the presence of structural calcium and the type of inhibitor resulted in differences in structural stability and in the map of protein-ligand and protein-protein interactions. Overall, our results suggest that the heterodimer complex and structural calcium are linked to the binding properties of PL.

  19. A high molecular weight protease in liver cytosol.

    PubMed

    Rose, I A; Warms, J V; Hershko, A

    1979-09-10

    A high molecular weight (greater than 400,000) protease active with [3H]leucine-labeled globin has been found in the postmicrosomal fraction of mouse kidney, brain, heart, spleen, and tumor cells and is most active in liver. The presence in liver was unexpected because liver cytosol is very ineffective in the breakdown of endogenous, labeled proteins. The enzyme has a number of properties that distinguish it from known cathepsins in addition to its high molecular weight. It is most active at pH approximately 7.5. When purified, it is unstable above 20 degrees C and is stabilized by metal chelating agents such as citrate, creatine-P, and glycerate-3-P. It is an -SH protease, but its thermal instability is not affected by 1 mM dithiothreitol. The enzyme is not lysosomal.

  20. Molecular weight characterization of single globular proteins using optical nanotweezers.

    PubMed

    Wheaton, Skyler; Gordon, Reuven

    2015-07-21

    We trap a set of molecular weight standard globular proteins using a double nanohole optical trap. The root mean squared variation of the trapping laser transmission intensity gives a linear dependence with the molecular weight, showing the potential for analysis of globular proteins. The characteristic time of the autocorrelation of the trapping laser intensity variations scales with a -2/3 power dependence with the volume of the particle. A hydrodynamic laser tweezer model is used to explain these dependencies. Since this is a single particle technique that operates in solution and can be used to isolate an individual particle, we believe that it provides an interesting alternative to existing analysis methods and shows promise to expand the capabilities of protein related studies to the single particle level.

  1. High molecular weight polysaccharide that binds and inhibits virus

    DOEpatents

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  2. Ultra-High-Molecular-Weight Silphenylene/Siloxane Elastomers

    NASA Technical Reports Server (NTRS)

    Hundley, N. H.; Patterson, W. J.

    1989-01-01

    Elastomers enhance thermal and mechancial properties. Capable of performing in extreme thermal/oxidative environments and having molecular weights above 10 to the sixth power prepared and analyzed in laboratory experiments. Made of methylvinylsilphenylene-siloxane terpolymers, new materials amenable to conventional silicone-processing technology. Similarly formulated commercial methyl-vinyl silicones, vulcanized elastomers exhibit enhance thermal/oxidative stability and equivalent or superior mechanical properties.

  3. Virtual screening of RAGE inhibitors using molecular docking

    PubMed Central

    Devi Alaparthi, Malini; Gopinath, Gudipudi; Bandaru, Srinivas; Sankeshi, Venu; Mangalarapu, Madhavi; Sudha Nagamalla, Swetha; Sudhakar, Kota; Roja Rani, Anupalli; Rao Sagurthi, Someswar

    2016-01-01

    Advanced Glycation End products (AGEs) interaction with Receptor for AGEs (RAGE) activates downstream signaling and evokes inflammatory responses in vascular cells. Therefore, it is of interest to design a novel series of molecules with a library of 352 compounds based on natural Isoflavone and Argpyrimidine moities. The compounds screened against the optimized structure of RAGE (PDB code: 3CJJ) using MolDock aided with molecular docking algorithm. This exercise identified compound number 62 with appreciable ADME properties having no toxicity and pharmacophore features. Therefore, compound 62 identified as a RAGE inhibitor is proposed for further validation in the context of Diabetic Retinopathy (DR) and vascular complications. PMID:28149046

  4. Comparison of antimicrobial activities of newly obtained low molecular weight scorpion chitosan and medium molecular weight commercial chitosan.

    PubMed

    Kaya, Murat; Asan-Ozusaglam, Meltem; Erdogan, Sevil

    2016-06-01

    In this study the antimicrobial activity of low molecular weight (3.22 kDa) chitosan, obtained for the first time from a species belonging to the Scorpiones, was screened against nine pathogenic microorganisms (seven bacteria and two yeasts) and compared with that of medium molecular weight commercial chitosan (MMWCC). It was observed that the antimicrobial activity of the low molecular weight scorpion chitosan (LMWSC) was specific to bacterial species in general rather than gram-negative or gram-positive bacterial groups. It was also determined that LMWSC had a stronger inhibitory effect than the MMWCC, particularly on the bacterium Listeria monocytogenes and the yeast Candida albicans, which are important pathogens for public health. In addition, it was recorded that the MMWCC had a greater inhibitory effect on Bacillus subtilis than LMWSC. According to the results obtained by the disc diffusion method, the antibacterial activity of both LMWSC and MMWCC against B. subtilis and Salmonella enteritidis was higher than the widely used antibiotic Gentamicin (CN, 10 μg/disc).

  5. Stable, concentrated solutions of high molecular weight polyaniline and articles therefrom

    DOEpatents

    Mattes, Benjamin R.; Wang, Hsing-Lin

    2000-01-01

    Stable, concentrated solutions of high molecular weight polyaniline. In order to process high quality fibers and other articles possessing good mechanical properties, it is known that solution concentrations of the chosen polymer should be in the range from 15-30% (w/w). Moreover, it is desirable to use the highest molecular weight consistent with the solubility properties of the polymer. However, such solutions are inherently unstable, forming gels before processing can be achieved. The present invention describes the addition gel inhibitors (GIs) to the polymer solution, thereby permitting high concentrations (>15% (w/w)) of high molecular weight ((M.sub.w)>120,000, and (M.sub.n)>30,000) emeraldine base (EB) polyaniline to be dissolved. Secondary amines have been used for this purpose in concentrations which are small compared to those which might otherwise be used in a cosolvent role therefor. The resulting solutions are useful for generating excellent fibers, films, coatings and other objects, since the solutions are stable for significant time periods, and the GIs are present in too small concentrations to cause polymer deterioration. It is demonstrated that the GIs found to be useful do not act as cosolvents, and that gelation times of the solutions are directly proportional to the concentration of GI. In particular, there is a preferred concentration of GI, which if exceeded causes structural and electrical conductivity degradation of resulting articles. Heating of the solutions significantly improves solubility.

  6. Stable, concentrated solutions of high molecular weight polyaniline and articles therefrom

    DOEpatents

    Mattes, Benjamin R.; Wang, Hsing-Lin

    1999-11-09

    Stable, concentrated solutions of high molecular weight polyaniline. In order to process high quality fibers and other articles possessing good mechanical properties, it is known that solution concentrations of the chosen polymer should be in the range from 15-30% (w/w). Moreover, it is desirable to use the highest molecular weight consistent with the solubility properties of the polymer. However, such solutions are inherently unstable, forming gels before processing can be achieved. The present invention describes the addition gel inhibitors (GIs) to the polymer solution, thereby permitting high concentrations (between 15% and 30% (w/w)) of high molecular weight ((M.sub.w)>120,000, and (M.sub.n)>30,000) emeraldine base (EB) polyaniline to be dissolved. Secondary amines have been used for this purpose in concentrations which are small compared to those which might otherwise be used in a cosolvent role therefor. The resulting solutions are useful for generating excellent fibers, films, coatings and other objects, since the solutions are stable for significant time periods, and the GIs are present in too small concentrations to cause polymer deterioration. It is demonstrated that the GIs found to be useful do not act as cosolvents, and that gelation times of the solutions are directly proportional to the concentration of GI. In particular, there is a preferred concentration of GI, which if exceeded causes structural and electrical conductivity degradation of resulting articles. Heating of the solutions significantly improves solubility.

  7. High Sulfation and a High Molecular Weight Are Important for Anti-hepcidin Activity of Heparin

    PubMed Central

    Asperti, Michela; Naggi, Annamaria; Esposito, Emiliano; Ruzzenenti, Paola; Di Somma, Margherita; Gryzik, Magdalena; Arosio, Paolo; Poli, Maura

    2016-01-01

    Heparins are efficient inhibitors of hepcidin expression even in vivo, where they induce an increase of systemic iron availability. Heparins seem to act by interfering with BMP6 signaling pathways that control the expression of liver hepcidin, causing the suppression of SMAD1/5/8 phosphorylation. The anti-hepcidin activity persists also when the heparin anticoagulant property is abolished or reduced by chemical reactions of oxidation/reduction (glycol-split, Gs-Heparins) or by high sulfation (SS-Heparins), but the structural characteristics needed to optimize this inhibitory activity have not been studied in detail. To this aim we analyzed three different heparins (Mucosal Heparin, the Glycol split RO-82, the partially desulfated glycol-split RO-68 and the oversulfated SSLMWH) and separated them in fractions of molecular weight in the range 4–16 kD. Since the distribution of the negative charges in heparins contributes to the activity, we produced 2-O- and 6-O-desulfated heparins. These derivatives were analyzed for the capacity to inhibit hepcidin expression in hepatic HepG2 cells and in mice. The two approaches produced consistent results and showed that the anti-hepcidin activity strongly decreases with molecular weight below 7 kD, with high N-acetylation and after 2-O and 6-O desulfation. The high sulfation and high molecular weight properties for efficient anti-hepcidin activity suggest that heparin is involved in multiple binding sites. PMID:26955355

  8. Influence of Molecular Weight on the Mechanical Performance of a Thermoplastic Glassy Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.; Hinkley, Jeffrey A.

    1999-01-01

    Mechanical Testing of an advanced thermoplastic polyimide (LaRC-TM-SI) with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. The physical characterization, elastic properties and notched tensile strength were all determined as a function of molecular weight and test temperature. It was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature. A critical molecular weight (Mc) was observed to occur at a weight-average molecular weight (Mw) of approx. 22000 g/mol below which, the notched tensile strength decreases rapidly. This critical molecular weight transition is temperature-independent. Furthermore, inelastic analysis showed that low molecular weight materials tended to fail in a brittle manner, whereas high molecular weight materials exhibited ductile failure. The microstructural images supported these findings.

  9. Impact resistance and fractography in ultra high molecular weight polyethylenes.

    PubMed

    Puértolas, J A; Pascual, F J; Martínez-Morlanes, M J

    2014-02-01

    Highly crosslinked ultra high molecular weight polyethylenes (UHMWPE) stabilized by a remelting process or by the addition of an antioxidant are highly wear resistant and chemically stable. However, these polyethylenes currently used in total joint replacements suffer a loss of mechanical properties, especially in terms of fracture toughness. In this study we analyze the impact behavior of different polyethylenes using an instrumented double notch Izod test. The materials studied are three resins: GUR1050, GUR1020 with 0.1wt% of vitamin E, and MG003 with 0.1wt% of vitamin E. These resins were gamma irradiated at 90kGy, and pre and post-irradiation remelting processes were applied to GUR1050 for two different time periods. Microstructural data were determined by means of differential scanning calorimetry and transmission electron microscopy. Fractography carried out on the impact fracture surfaces and images obtained by scanning electron microscopy after etching indicated the existence of a fringe structure formed by consecutive ductile-brittle and brittle-ductile transitions, which is related to the appearance of discontinuities in the load-deflection curves. A correlation has been made of the macroscopic impact strength results and the molecular chain and microstructural characteristics of these aforementioned materials, with a view to designing future resins with improved impact resistance. The use of UHMWPE resins with low molecular weight or the application of a remelting treatment could contribute to obtain a better impact strength behavior.

  10. Effect of weight loss on high-molecular weight adiponectin in obese children.

    PubMed

    Martos-Moreno, Gabriel Á; Barrios, Vicente; Martínez, Guillermo; Hawkins, Federico; Argente, Jesús

    2010-12-01

    Our aim was to determine the influence of weight reduction on total (T-) and high-molecular weight (HMW-) adiponectin in obese (OB) prepubertal children. Seventy OB prepubertal white patients were followed for 18 months and studied after reducing their BMI by 1 (n = 51) and 2 standard deviation scores (SDS) (n = 21) under conservative treatment, and 6 months after achieving weight loss (n = 44). Body composition dual-energy X-ray absorptiometry (DXA) and serum levels of T- and HMW-adiponectin, resistin, leptin, leptin soluble receptor (sOB-R), tumoral necrosis factor-α and interleukin-6 were determined. The control group consisted of 61 healthy prepubertal children. At diagnosis T-adiponectin was higher (P < 0.01; confidence interval (+0.04) - (+0.15)) and HMW-adiponectin lower (P < 0.001; confidence interval (-0.45) - (-0.21)) in OB children than in controls. A reduction in body fat increased T- and HMW-adiponectin and sOB-R (all P < 0.001) and decreased leptin (P < 0.001) and interleukin-6 levels (P < 0.05). After 6 months of sustained weight reduction a decrease in tumoral necrosis factor-α (P < 0.01) occurred, whereas weight recovery increased leptin (P < 0.001) and decreased T-adiponectin (P < 0.05). HMW-adiponectin levels negatively correlated with homeostasis model assessment (HOMA) index and BMI in the whole cohort (both P < 0.001), as did T-adiponectin levels and HOMA index in OB patients (P < 0.01), but neither T- nor HMW-adiponectin correlated with body fat content (BFC) in OB children. We conclude that the impairment of T- and HMW-adiponectin levels in childhood obesity is different to that in elder OB patients, showing closer relationship with carbohydrate metabolism parameters than with BFC, but increasing their levels after weight loss and in association with metabolic improvement.

  11. Conformations of low-molecular-weight lignin polymers in water

    SciTech Connect

    Petridis, Loukas; Smith, Jeremy C.

    2016-01-13

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a critical degree of polymerization, Nc=15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. As a result, an implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures.

  12. Conformations of Low-Molecular-Weight Lignin Polymers in Water.

    PubMed

    Petridis, Loukas; Smith, Jeremy C

    2016-02-08

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a critical degree of polymerization, Nc =15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. An implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures.

  13. Conformations of low-molecular-weight lignin polymers in water

    DOE PAGES

    Petridis, Loukas; Smith, Jeremy C.

    2016-01-13

    Low-molecular-weight lignin binds to cellulose during the thermochemical pretreatment of biomass for biofuel production, which prevents the efficient hydrolysis of the cellulose to sugars. The binding properties of lignin are influenced strongly by the conformations it adopts. Here, we use molecular dynamics simulations in aqueous solution to investigate the dependence of the shape of lignin polymers on chain length and temperature. Lignin is found to adopt collapsed conformations in water at 300 and 500 K. However, at 300 K, a discontinuous transition is found in the shape of the polymer as a function of the chain length. Below a criticalmore » degree of polymerization, Nc=15, the polymer adopts less spherical conformations than above Nc. The transition disappears at high temperatures (500 K) at which only spherical shapes are adopted. As a result, an implication relevant to cellulosic biofuel production is that lignin will self-aggregate even at high pretreatment temperatures.« less

  14. Biliary excretion in dogs: evidence for a molecular weight threshold.

    PubMed

    Yang, Xinning; Gandhi, Yash A; Morris, Marilyn E

    2010-04-16

    Molecular weight (MW) is known as an important factor of biliary excretion in rats, guinea pigs, rabbits and humans. The objective of this study was to evaluate the relationship between the biliary excretion and MW of drugs in dogs. Data on the percentage of dose excreted into bile as parent drug (PD(b)) in dogs were collected from the literature for 134 compounds. Receiver operating characteristic (ROC) curve analysis was utilized to determine whether a MW threshold exists for PD(b). A MW threshold of 375-400 Da was established for anions in dogs, which is similar with the cutoff value observed in rats (400 Da) but lower than the one in humans (475 Da). No MW threshold was found for cations or cations/neutral compounds. A molecular volume threshold of 300A(3) was also determined for anions in dogs, which corresponds to a MW of 394 Da. In conclusion, our analysis suggested the presence of a MW cutoff for anions in dogs, which may be related with the molecular size of a compound. This represents the first report of the influence of MW or molecular volume as a determinant of biliary excretion for a structurally diverse set of compounds in dogs.

  15. Controlling silk fibroin microspheres via molecular weight distribution.

    PubMed

    Zeng, Dong-Mei; Pan, Jue-Jing; Wang, Qun; Liu, Xin-Fang; Wang, Hui; Zhang, Ke-Qin

    2015-05-01

    Silk fibroin (SF) microspheres were produced by salting out SF solution via the addition of potassium phosphate buffer solution (K2HPO4-KH2PO4). The morphology, size and polydispersity of SF microspheres were adjusted by changing the molecular weight (MW) distribution and concentration of SF, as well as the ionic strength and pH of the buffer solution. Changing the conditions under which the SF fiber dissolved in the Lithium Boride (LiBr) solution resulted in altering the MW distribution of SF solution. Under optimal salting-out conditions (ionic strength>0.7 M and pH>7) and using a smaller and narrower SF MW distribution, SF microspheres with smoother shapes and more uniform sizes were produced. Meanwhile, the size and polydispersity of the microspheres increased when the SF concentration was increased from 0.25 mg/mL to 20 mg/mL. The improved SF microspheres, obtained by altering the distribution of molecular weight, have potential in drug and gene delivery applications.

  16. Determination of molecular weight distributions in native and pretreated wood.

    PubMed

    Leskinen, Timo; Kelley, Stephen S; Argyropoulos, Dimitris S

    2015-03-30

    The analysis of native wood components by size-exclusion chromatography (SEC) is challenging. Isolation, derivatization and solubilization of wood polymers is required prior to the analysis. The present approach allowed the determination of molecular weight distributions of the carbohydrates and of lignin in native and processed woods, without preparative component isolation steps. For the first time a component selective SEC analysis of sawdust preparations was made possible by the combination of two selective derivatization methods, namely; ionic liquid assisted benzoylation of the carbohydrate fraction and acetobromination of the lignin in acetic acid media. These were optimized for wood samples. The developed method was thus used to examine changes in softwood samples after degradative mechanical and/or chemical treatments, such as ball milling, steam explosion, green liquor pulping, and chemical oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The methodology can also be applied to examine changes in molecular weight and lignin-carbohydrate linkages that occur during wood-based biorefinery operations, such as pretreatments, and enzymatic saccharification.

  17. Impact of molecular weight in four-branched star vectors with narrow molecular weight distribution on gene delivery efficiency.

    PubMed

    Nemoto, Yasushi; Borovkov, Alexey; Zhou, Yue-Min; Takewa, Yoshiaki; Tatsumi, Eisuke; Nakayama, Yasuhide

    2009-12-01

    A series of star-shaped cationic polymers, termed star vectors (SVs), has been developed as effective nonviral gene delivery carriers. In this study, we separated SVs into several fractions having different molecular weights with very narrow molecular weight distributions in order to examine in detail the influence of the molecular weight of the SVs on the gene transfection efficiency. As a model compound for several types of SVs, 4-branched poly(N,N-dimethylaminopropyl acrylamide) having a molecular weight (M(n)) of approximately 35 kDa and polydispersity of 1.6 was prepared by iniferter-based radical polymerization. The SVs were separated using size-exclusion chromatography to obtain seven fractions having M(n) ranging from 27 kDa to 73 kDa with polydispersity ranging from 1.1 to 1.2. All the fractionated SVs have similar pH of 10.2-10.4 and were able to interact with and condense luciferase-encoding plasmid deoxyribonucleic acid (DNA) to yield SV/DNA polyplexes. A water-soluble tetrazolium-1 (WST) assay showed that all SVs had minimal cellular cytotoxicity under an N/P charge ratio of 10. The critical micellar concentration decreased with an increase in the M(n) of the fractionated SVs; however, the particle size of the polyplexes, exclusion activity of ethidium bromide, and zeta-potential of the polyplexes increased. An in vitro evaluation using COS-1 cells at an N/P ratio of 10 showed that transfection activity increased almost linearly with M(n). The highest transfection activity was obtained for SVs with the highest M(n) (73 kDa), which was over 7 times that for the SVs with the lowest M(n) (27 kDa), the nonfractionated original SV, or PEI standard. The transfection efficiency was more correlated with the amphiphilicity or hydrophobicity of the SVs and the surface potential and condensate density of the polyplexes than with the particle size.

  18. Viscoelastic Behavior of Low Molecular Weight Sulfonated Polystyrene Ionomers

    NASA Astrophysics Data System (ADS)

    Zhao, Hongying

    Ionomers are those hydrophobic polymers having small amounts of bonded ionic groups. The introduction of the ionic groups into polymer chain produces large changes in the physical, mechanical and rheological properties of the parent polymer. Characterization of the effect of the ionic interactions on the rheology is complicated by the difficulty in separating effects due to molecular entanglements and the ionic interactions. In this study, low molecular weight (Mw=4000) sulfonated polystyrene (SPS) was used to study the dynamic and steady shear rheology of SPS ionomers. The polymer chain length used was far below the entanglement molecular weight of polystyrene and effects of molecular entanglements will be absent. Any polymer chain entanglements or lengthening behavior on the melt rheology should be due to the ionic interactions. Random SPS ionomers with two sulfonation levels were examined, 2.5 and 4.8 mol%, which corresponded, respectively, to one and two sulfonate groups per chain on average. The metal counterions was varied across the alkali metal series of the periodic table. Morphology of the ionomer was characterized by using small angle x-ray scattering (SAXS) analysis, and dynamic and steady shear measurements were performed to investigate rheological behavior of the ionomers. Glass transition temperatures of the ionomers increased with increasing ion concentration but were insensitive to cation used. The scattering peak in SAXS indicates the existence of the nanophase separated ionic clusters. The strong ionic nanophase persist up to very high temperatures and is not sensitive to the external stress. Time-temperature superposition (TTS) of G' worked reasonably well while TTS of G" failed for most ionomers. Ionic interactions increased the terminal relaxation time of the melts as much as seven orders of magnitude greater than the unentangled PS melt. The zero shear viscosity and first normal stress coefficients scaled with cq/a, where c was the

  19. Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

    PubMed Central

    do Nascimento Campos Ribeiro, Joycellane Alline; Serquiz, Alexandre Coellho; dos Santos Silva, Priscila Fabíola; Barbosa, Patrícia Batista Barra Medeiros; Sampaio, Tarcísio Bruno Montenegro; de Araújo, Raimundo Fernandes; de Oliveira, Adeliana Silva; Machado, Richele Janaina Araújo; Maciel, Bruna Leal Lima; Uchôa, Adriana Ferreira; dos Santos, Elizeu Antunes; de Araújo Morais, Ana Heloneida

    2015-01-01

    OBJECTIVES: Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats. METHODS: A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30–60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed. RESULTS: The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water. CONCLUSION: The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated. PMID:25789523

  20. Low molecular weight silicones particularly facilitate human serum albumin denaturation.

    PubMed

    Nayef, Lamees M; Khan, Madiha F; Brook, Michael A

    2015-04-01

    There is a market trend towards the administration of therapeutic proteins using sterilized, pre-filled glass syringes lubricated with silicone oil. It has been widely reported that initially clear solutions of proteins can become turbid during transport and storage, with unclear outcomes with respect to bioefficacy. While the basic processes of interactions of proteins with hydrophobic entities, leading to denaturation and aggregation, are increasingly well understood, the apparently random occurrence of such processes in syringes is not. To better understand the parameters that may be responsible for this change, we report the systematic examination of a series of factors that can affect the behavior of the protein human serum albumin (HSA) when in contact with silicone oil in water. Fluorescence spectroscopy showed that greater mixing times and greater concentrations of silicones (polydimethylsiloxane (PDMS)), especially lower molecular weight hydrophobic silicones like octamethyltetracyclosiloxane (D4), were associated with increased protein denaturation. The turbidity of HSA solutions, due to the formation both of silicone oil-in-water (O/W) emulsions and protein aggregates, was also facilitated by the presence of D4. A series of mixtures of silicone oils, all of which exhibited a viscosity of 1000 cSt but which were comprised of different silicone constituents, clearly showed a correlation between the presence of lower molecular silicones and enhanced solution turbidity. While the addition of a non-ionic silicone-polyether surfactant led to greater turbidity by increasing the number of stabilized oil droplets, it was not accompanied by protein denaturation. These results are consistent with HSA denaturation and subsequent aggregation as a consequence of contact particularly with low molecular weight, hydrophobic silicones that are more mobile, leading to more efficient protein/silicone contact.

  1. Molecular biology and inhibitors of hepatitis A virus.

    PubMed

    Debing, Yannick; Neyts, Johan; Thibaut, Hendrik Jan

    2014-09-01

    Hepatitis A virus (HAV) is a faeco-orally transmitted picornavirus and is one of the main causes of acute hepatitis worldwide. An overview of the molecular biology of HAV is presented with an emphasis on recent findings. Immune evasion strategies and a possible correlation between HAV and atopy are discussed as well. Despite the availability of efficient vaccines, antiviral drugs targeting HAV are required to treat severe cases of fulminant hepatitis, contain outbreaks, and halt the potential spread of vaccine-escape variants. Additionally, such drugs could be used to shorten the period of illness and decrease associated economical costs. Several known inhibitors of HAV with various mechanisms of action will be discussed. Since none of these molecules is readily useable in the clinic and since the availability of an anti-HAV drug would be of clinical importance, increased efforts should be targeted toward discovery and development of such antivirals.

  2. Tuning the superstructure of ultrahigh-molecular-weight polyethylene/low-molecular-weight polyethylene blend for artificial joint application.

    PubMed

    Xu, Ling; Chen, Chen; Zhong, Gan-Ji; Lei, Jun; Xu, Jia-Zhuang; Hsiao, Benjamin S; Li, Zhong-Ming

    2012-03-01

    An easy approach was reported to achieve high mechanical properties of ultrahigh-molecular-weight polyethylene (UHMWPE)-based polyethylene (PE) blend for artificial joint application without the sacrifice of the original excellent wear and fatigue behavior of UHMWPE. The PE blend with desirable fluidity was obtained by melt mixing UHMWPE and low molecular weight polyethylene (LMWPE), and then was processed by a modified injection molding technology-oscillatory shear injection molding (OSIM). Morphological observation of the OSIM PE blend showed LMWPE contained well-defined interlocking shish-kebab self-reinforced superstructure. Addition of a small amount of long chain polyethylene (2 wt %) to LMWPE greatly induced formation of rich shish-kebabs. The ultimate tensile strength considerably increased from 27.6 MPa for conventional compression molded UHMWPE up to 78.4 MPa for OSIM PE blend along the flow direction and up to 33.5 MPa in its transverse direction. The impact strength of OSIM PE blend was increased by 46% and 7% for OSIM PE blend in the direction parallel and vertical to the shear flow, respectively. Wear and fatigue resistance were comparable to conventional compression molded UHMWPE. The superb performance of the OSIM PE blend was originated from formation of rich interlocking shish-kebab superstructure while maintaining unique properties of UHMWPE. The present results suggested the OSIM PE blend has high potential for artificial joint application.

  3. Expression of low molecular weight proteins in patients with leukaemia.

    PubMed

    Sheikh, N; Abid, R; Qureshi, A W; Basheer, T

    2012-06-01

    The current study is conducted to observe the differences in the level of low molecular weight proteins in the sera of patients with leukaemia in comparison to healthy subjects (control group). The sera of patients with leukaemia showed 15 peaks in the densitometric curve in comparison to the seven peaks of the controls. The peaks in the experimental samples that coincide with those in the control were of 134.14, 113.15, 76.06, 63.25, 48.07, 22.85 and 16.47 kDa molecular weights, respectively. Most of the new peaks appeared between the proteins of molecular weight 36-29 kDa in the experimental groups. Mean density of the 134.14 kDa protein band showed an increase in the protein in experimental groups I and II only whereas 113.15 and 22.85 kDa protein were increased in all experimental groups of patients with leukaemia. The expression of 76.06 and 63.25 kDa protein fraction was downregulated in the patients with leukaemia. A decline in the level of the protein of 48.07 kDa was observed in patients with leukaemia except in group I. Unlike the other protein fractions, the level of the protein of 16.47 kDa was significantly (p < 0.05) increased with a maximum density in group II. Intergroup experimental) comparison revealed an increasing pattern of 95.44 and 89.21 kDa with maximum level in group III sera. However the protein fractions of 38.07 and 34.94 kDa varied in the serum with maximum density in Group IV Protein fractions of 32.92 and 31.24 kDa were expressed in all age groups of patients with leukaemia with a maximum density in group III whereas the percentage densities of 14.42 and 13.56 kDa protein were quite different. This preliminary study will provide a basis to study the role of different proteins in patients with leukaemia.

  4. Mechanical Properties of LaRC(tm) SI Polymer for a Range of Molecular Weights

    NASA Technical Reports Server (NTRS)

    Whitley, Karen S.; Gates, Thomas S.; Hinkley, Jeffrey A.; Nicholson, Lee M.

    2000-01-01

    Mechanical testing of an advanced polyimide resin (LaRC(tm)-SI) with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. Elastic and inelastic properties were characterized as a function of molecular weight and test temperature. It was shown that notched tensile strength is a strong function of both temperature and molecular weight, whereas stiffness is only a strong function of temperature. The combined analysis of calculated yield stress and notched tensile strength indicated that low molecular weight materials tended to fail in a brittle manner, whereas high molecular weight materials exhibited ductile failure. The microphotographs of the failure surfaces also supported these findings.

  5. Purification of a low molecular weight fucoidan for SPECT molecular imaging of myocardial infarction.

    PubMed

    Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Azzouna, Rana Ben; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Guludec, Dominique Le; Letourneur, Didier; Chauvierre, Cédric

    2014-09-23

    Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome.

  6. Biological effects of high molecular weight lignin derivatives.

    PubMed

    Pessala, Piia; Schultz, Eija; Kukkola, Jukka; Nakari, Tarja; Knuutinen, Juha; Herve, Sirpa; Paasivirta, Jaakko

    2010-10-01

    A number of high molecular weight (HMW) lignin derivatives possessing varied chemical properties were screened for their biological effects in order to obtain more information on the possible structural features of HMW lignin-related effects. The studied compounds were both commercial and in-house extracted lignin derivatives. Bioassays used include reverse electron transport (RET), Vibrio fischeri, Daphnia magna, and juvenile rainbow trout (Oncorhynchus mykiss) hepatocytes. The studied lignin derivatives inhibited the in vitro systems and luminescence of V. fischeri bacteria to some extent-daphnids were not affected. It seems that, at least in the RET assay, certain pH-dependent functional groups in lignin may be of importance regarding the biological effects.

  7. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, S.; Benner, W.H.; Madden, N.M.; Searles, W.

    1998-06-23

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e{sup {minus}} are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation. 14 figs.

  8. Apparatus and method of determining molecular weight of large molecules

    DOEpatents

    Fuerstenau, Stephen; Benner, W. Henry; Madden, Norman; Searles, William

    1998-01-01

    A mass spectrometer determines the mass of multiply charged high molecular weight molecules. This spectrometer utilizes an ion detector which is capable of simultaneously measuring the charge z and transit time of a single ion as it passes through the detector. From this transit time, the velocity of the single ion may then be derived, thus providing the mass-to-charge ratio m/z for a single ion which has been accelerated through a known potential. Given z and m/z, the mass m of the single ion can then be calculated. Electrospray ions with masses in excess of 1 MDa and charge numbers greater than 425 e.sup.- are readily detected. The on-axis single ion detection configuration enables a duty cycle of nearly 100% and extends the practical application of electrospray mass spectrometry to the analysis of very large molecules with relatively inexpensive instrumentation.

  9. Hydrophobic composition based on mixed-molecular weight polyethylene

    NASA Astrophysics Data System (ADS)

    Gorlenko, Nikolay; Debelova, Natalya; Sarkisov, Yuriy; Volokitin, Gennadiy; Zavyalova, Elena; Lapova, Tatyana

    2016-01-01

    The paper presents investigations of compositions based on low and high molecular weight polyethylene so as to synthesize a hydrophobic composition for moisture protection of timber. X-ray phase analysis and measurements of the tear-off force of hydrophobic coating needed to apply to the timber surface and the limiting wetting angle are carried out to detect the hydrophobic, adhesive, electrophysical, and physicochemical properties of compositions. Kinetic dependencies are given for moisture absorption of timber specimens. It is shown that the preliminary formation of the texture by the surface patterning or its treatment with low-temperature plasma with the following protective coating results in the improvement of hydrophobic properties of the suggested compositions. These compositions can be used in the capacity of water repellents to protect building materials from moisture including restoration works.

  10. Methyl Methacrylate Polymerization in Nanoporous Matrix: Reactivity and Molecular Weight

    NASA Astrophysics Data System (ADS)

    Zhao, Haoyu; Simon, Sindee

    2011-03-01

    The influence of nanoconfinement on the free radical polymerization of methyl methacrylate is investigated. Nanoporous controlled pore glass (CPG) is used as a nanoconfining matrix for the polymerization. The reaction is followed by measuring heat flow as a function of reaction time during isothermal polymerization using differential scanning calorimetry (DSC). Preliminary results indicate several interesting effects for polymerization in 110 nm diameter pores: the induction time increases under nanoconfinement, the effective reaction rate constant increases, the effective activation energy is unchanged, and the gel effect or autoaccleration occurs at earlier times after induction. The latter result concerning the gel effect is presumably due to the decrease in diffusivity under nanoconfinement which results in a decrease in the termination rate of free radicals. The cause of the longer induction times and accelerated reaction rates just after induction are under investigation. The influence of nanoconfinement on molecular weight will also be examined.

  11. Dairy Wastewater Treatment Using Low Molecular Weight Crab Shell Chitosan

    NASA Astrophysics Data System (ADS)

    Geetha Devi, M.; Dumaran, Joefel Jessica; Feroz, S.

    2012-08-01

    The investigation of possible use of low molecular weight crab shell chitosan (MW 20 kDa) in the treatment of dairy waste water was studied. Various experiments have been carried out using batch adsorption technique to study the effects of the process variables, which include contact time, stirring speed, pH and adsorbent dosage. Treated effluent characteristics at optimum condition showed that chitosan can be effectively used as adsorbent in the treatment of dairy wastewater. The optimum conditions for this study were at 150 mg/l of chitosan, pH 5 and 50 min of mixing time with 50 rpm of mixing speed. Chitosan showed the highest performance under these conditions with 79 % COD, 93 % turbidity and 73 % TSS reduction. The result showed that chitosan is an effective coagulant, which can reduce the level of COD, TSS and turbidity in dairy industry wastewater.

  12. The versatile low-molecular-weight thiols: Beyond cell protection.

    PubMed

    Wang, Min; Zhao, Qunfei; Liu, Wen

    2015-12-01

    Low-molecular-weight (LMW) thiols are extensively involved in the maintenance of cellular redox potentials and the protection of cells from a variety of reactive chemical and electrophilic species. However, we recently found that the metabolic coupling of two LMW thiols - mycothiol (MSH) and ergothioneine (EGT) - programs the biosynthesis of the anti-infective agent lincomycin A. Remarkably, such a constructive role of the thiols in the biosynthesis of natural products has so far received relatively little attention. We speculate that the unusual thiol EGT might function as a chiral thiolation carrier (for modification) and a novel activator (for glycosylation) of sugar. Additionally, we examine recent evidence for LMW thiols (MSH and others) as sulfur donors of sulfur-containing natural products. Clearly, the LMW thiols have more diverse activities beyond cell protection, and more attention should be paid to the correlation of their functions with thiol-dependent enzymes.

  13. Ultra-high molecular weight silphenylene-siloxane polymers

    NASA Technical Reports Server (NTRS)

    Patterson, W. J.; Hundley, N. H.; Ludwick, L. M.

    1984-01-01

    Silphenylene-siloxane copolymers with molecular weights above one million were prepared using a two stage polymerization technique. The technique was successfully scaled up to produce 50 grams of this high polymer in a single run. The reactive monomer approach was also investigated using the following aminosilanes: bis(dimethylamino)dimethylsilane, N,N-bis(pyrrolidinyl)dimethylsilane and N,N-bis(gamma-butyrolactam)dimethylsilane). Thermal analyses were performed in both air and nitrogen. The experimental polymers decomposed at 540 to 562 C, as opposed to 408 to 426 C for commercial silicones. Differential scanning calorimetry showed a glass transition (Tg) at -50 to -55 C for the silphenylene-siloxane copolymer while the commercial silicones had Tg's at -96 to -112 C.

  14. Molecular weight degradation and rheological properties of schizophyllan under ultrasonic treatment.

    PubMed

    Zhong, Kui; Zhang, Qi; Tong, Litao; Liu, Liya; Zhou, Xianrong; Zhou, Sumei

    2015-03-01

    Molecular weight degradation effects of schizophyllan (SPG) under ultrasonic treatments were investigated in this study. The degradation product was treated by alcohol fractional precipitation technology, and the molecular weight and rheological properties of ultrasonic-treated SPG (USPG) fractions were evaluated. Average molecular weight of SPG decreased significantly after ultrasonic treatments, and degradation product had more narrow distribution of molecular weight. The molecular weight degradation kinetics of SPG is adequately described by a second-order reaction. USPG fractions with different molecular weight were obtained by fractional precipitation for final alcohol concentration fractions 0-40%, 40-60% and 60-80%, respectively. USPG fractions had near-Newtonian flow behaviors, and USPG₈₀% exhibited viscous responses over the entire accessible frequency range. Therefore, ultrasonic treatment is a viable modification technology for SPG and other polymer materials with high molecular weight.

  15. Low-molecular-weight heparin in pediatric patients.

    PubMed

    Sutor, Anton Heinz; Chan, Anthony K C; Massicotte, Patricia

    2004-02-01

    The incidence of thromboembolic events (TEs) in childhood is greatly underestimated. Two age groups account for approximately 70% of TEs in childhood: infants and teenagers. There are several predisposing risk factors for newborns such as small vessels, high hematocrit, and a unique neonatal hemostatic system. Central venous lines contribute to 80% of deep vein thrombosis in newborns. Other risk factors for all children are shock syndromes, trauma, surgery, heart and kidney disease, and acquired or hereditary thrombophilias. The best prophylaxis is to recognize, avoid, and remove risk factors if possible. This is particularly relevant in childhood, where risk factors can be found in the majority of TEs. The serious sequelae of TEs (mortality, and short- and long-term morbidity) require therapeutic intervention. Unfractionated heparin (UFH) has the following disadvantages: age-dependent unpredictable pharmacokinetics, the need for intravenous access for therapy and monitoring, delays in achieving therapeutic ranges, bleeding risk, the risk of heparin-induced thrombocytopenia, and osteoporosis with long-term use. Oral anticoagulants, in addition to some of these disadvantages, show considerable variation by diet (especially if there is a change from breast to bottle feeding), medication, and intercurrent illness. Review of case reports and cohort studies on 728 children treated with low-molecular-weight heparin (LMWH) indicate the following advantages over UFH: minimal monitoring, ease of administration (subcutaneous), and possibly equivalent efficacy and safety. Dose recommendations for pediatric patients cannot be directly extrapolated from those for adult patients. If dosages are calculated according to body weight, infants < 3 months (or < 5 kg) need approximately 50% more LMWH than older children or adults to reach prophylactic or therapeutic anti-factor Xa levels. Further studies are necessary to address the following: the importance of risk factors, the

  16. In situ reinforced polymers using low molecular weight compounds

    NASA Astrophysics Data System (ADS)

    Yordem, Onur Sinan

    2011-12-01

    The primary objective of this research is to generate reinforcing domains in situ during the processing of polymers by using phase separation techniques. Low molecular weight compounds were mixed with polymers where the process viscosity is reduced at process temperatures and mechanical properties are improved once the material system is cooled or reacted. Thermally induced phase separation and thermotropic phase transformation of low molar mass compounds were used in isotactic polypropylene (iPP) and poly(ether ether ketone) (PEEK) resins. Reaction induced phase separation was utilized in thermosets to generate anisotropic reinforcements. A new strategy to increase fracture toughness of materials was introduced. Simultaneously, enhancement in stiffness and reduction in process viscosity were also attained. Materials with improved rheological and mechanical properties were prepared by using thermotropic phase transformations of metal soaps in polymers (calcium stearate/iPP). Morphology and thermal properties were studied using WAXS, DSC and SEM. Mechanical and rheological investigation showed significant reduction in process viscosity and substantial improvement in fracture toughness were attained. Effects of molecular architecture of metal soaps were investigated in PEEK (calcium stearate/PEEK and sodium stearate/PEEK). The selected compounds reduced the process viscosity due to the high temperature co-continuous morphology of metal soaps. Unlike the iPP system that incorporates spherical particles, interaction between PEEK and metal soaps resulted in two discrete and co-continuous phases of PEEK and the metal stearates. DMA and melt rheology exhibited that sodium stearate/PEEK composites are stiffer. Effective moduli of secondary metal stearate phase were calculated using different composite theories, which suggested bicontinuous morphology to the metal soaps in PEEK. Use of low molecular weight crystallizable solvents was investigated in reactive systems

  17. Role of the kidney in the expression of low molecular weight factors with growth factor activity.

    PubMed

    Jacob, C; Maachi, F; el Farricha, O; Dousset, B; Kessler, M; Belleville, F; Nabet, P

    1993-06-01

    Small molecules of peptidic nature, called low molecular weight growth factors (LMW-GF < 1000 Da) are present in normal human serum ultrafiltrate. They enhance the somatomedin activity as measured by the incorporation of 35SO4 into chick embryo cartilages. On the basis of this in vitro test, LMW-GF activities were measured in serum ultrafiltrates of hemodialyzed patients and renal transplant recipients during the post-transplantation follow-up. LMW-GF activity was always zero in patients with chronic renal failure. It was checked that these results were not due to the presence of low molecular weight somatomedin inhibitors or to the increased sulfate concentration. After successful renal transplantation, the LMW-GF activity of patients ultrafiltrates returned to normal at the same time or before the improvement of renal function. In case of post-transplant complications, a decrease in LMW-GF activity accompanied or even occurred prior to impairment of renal function. In functioning graft, LMW-GF activity reappears rapidly, whereas its normalization is delayed in case of tubular nephropathy or episode of acute rejection. It was suggested that the kidney is involved in LMW-GF molecules production or processing. It could be speculated that LMW-GF activity might be a prognostic factor in renal transplantation.

  18. SGLT2 inhibitors: molecular design and potential differences in effect.

    PubMed

    Isaji, Masayuki

    2011-03-01

    The physiological and pathological handling of glucose via sodium-glucose cotransporter-2 (SGLT2) in the kidneys has been evolving, and SGLT2 inhibitors have been focused upon as a novel drug for treating diabetes. SGLT2 inhibitors enhance renal glucose excretion by inhibiting renal glucose reabsorption. Consequently, SGLT2 inhibitors reduce plasma glucose insulin independently and improve insulin resistance in diabetes. To date, various SGLT2 inhibitors have been developed and evaluated in clinical studies. The potency and positioning of SGLT2 inhibitors as an antidiabetic drug are dependent on their characteristic profile, which induces selectivity, efficacy, pharmacokinetics, and safety. This profile decides which SGLT2 inhibitors can be expected for application of the theoretical concept of reducing renal glucose reabsorption for the treatment of diabetes. I review the structure and advancing profile of various SGLT2 inhibitors, comparing their similarities and differences, and discuss the expected SGLT2 inhibitors for an emerging category of antidiabetic drugs.

  19. Optimization of parameters for coverage of low molecular weight proteins.

    PubMed

    Müller, Stephan A; Kohajda, Tibor; Findeiss, Sven; Stadler, Peter F; Washietl, Stefan; Kellis, Manolis; von Bergen, Martin; Kalkhof, Stefan

    2010-12-01

    Proteins with molecular weights of <25 kDa are involved in major biological processes such as ribosome formation, stress adaption (e.g., temperature reduction) and cell cycle control. Despite their importance, the coverage of smaller proteins in standard proteome studies is rather sparse. Here we investigated biochemical and mass spectrometric parameters that influence coverage and validity of identification. The underrepresentation of low molecular weight (LMW) proteins may be attributed to the low numbers of proteolytic peptides formed by tryptic digestion as well as their tendency to be lost in protein separation and concentration/desalting procedures. In a systematic investigation of the LMW proteome of Escherichia coli, a total of 455 LMW proteins (27% of the 1672 listed in the SwissProt protein database) were identified, corresponding to a coverage of 62% of the known cytosolic LMW proteins. Of these proteins, 93 had not yet been functionally classified, and five had not previously been confirmed at the protein level. In this study, the influences of protein extraction (either urea or TFA), proteolytic digestion (solely, and the combined usage of trypsin and AspN as endoproteases) and protein separation (gel- or non-gel-based) were investigated. Compared to the standard procedure based solely on the use of urea lysis buffer, in-gel separation and tryptic digestion, the complementary use of TFA for extraction or endoprotease AspN for proteolysis permits the identification of an extra 72 (32%) and 51 proteins (23%), respectively. Regarding mass spectrometry analysis with an LTQ Orbitrap mass spectrometer, collision-induced fragmentation (CID and HCD) and electron transfer dissociation using the linear ion trap (IT) or the Orbitrap as the analyzer were compared. IT-CID was found to yield the best identification rate, whereas IT-ETD provided almost comparable results in terms of LMW proteome coverage. The high overlap between the proteins identified with IT

  20. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar-Thermal Energy Storage.

    PubMed

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl; Moth-Poulsen, Kasper

    2016-09-05

    Molecular solar-thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193-260 g mol(-1) ) norbornadiene-quadricyclane systems. The molecules feature cyano acceptor and ethynyl-substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo-thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396-629 kJ kg(-1) ). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules.

  1. Low Molecular Weight Norbornadiene Derivatives for Molecular Solar‐Thermal Energy Storage

    PubMed Central

    Quant, Maria; Lennartson, Anders; Dreos, Ambra; Kuisma, Mikael; Erhart, Paul; Börjesson, Karl

    2016-01-01

    Abstract Molecular solar‐thermal energy storage systems are based on molecular switches that reversibly convert solar energy into chemical energy. Herein, we report the synthesis, characterization, and computational evaluation of a series of low molecular weight (193–260 g mol−1) norbornadiene–quadricyclane systems. The molecules feature cyano acceptor and ethynyl‐substituted aromatic donor groups, leading to a good match with solar irradiation, quantitative photo‐thermal conversion between the norbornadiene and quadricyclane, as well as high energy storage densities (396–629 kJ kg−1). The spectroscopic properties and energy storage capability have been further evaluated through density functional theory calculations, which indicate that the ethynyl moiety plays a critical role in obtaining the high oscillator strengths seen for these molecules. PMID:27492997

  2. Preparation of low-molecular-weight hyaluronic acid by ozone treatment.

    PubMed

    Wu, Yue

    2012-06-20

    Recently, low-molecular-weight hyaluronic acid has been reported to have novel features, such as free radical scavenging activities, antioxidant activities, promotion of excisional wound healing, etc. In the present work, degradation of native hyaluronic acid by ozone treatment was performed for preparation of low-molecular-weight hyaluronic acid. The molecular weight of native hyaluronic acid was reduced from 1535 to 87 kDa for 120 min at 40°C. The rate of reduction of molecular weight was 94.33%. The FT-IR, 13C NMR, and UV-vis spectra suggested that there was no obvious modification of chemical structure of low-molecular-weight hyaluronic acid. The use of degradation of native hyaluronic acid by ozone treatment can be a useful alternative for production of low-molecular-weight hyaluronic acid.

  3. Distribution of molecular weight in glyceride polymerizates or aggregates of them after contact with lunar grains

    NASA Technical Reports Server (NTRS)

    Asunmaa, S. K.; Haack, R.

    1977-01-01

    An attempt is made to report on experiments in which a molecular-weight increase was determined in thin layers of triglyceride-containing glycerides after thin-layer contact for two years with lunar topsoil grains at 25 C without any thermal activation. It is noted that solidification was observed on both dielectric grains and metal-rich areas and that changes in viscosity and molecular weights were first detected by solidification of surface layers. Gel permeation chromatography is described which detected a general shift of the Gaussian distribution of the molecular-weight data toward generally higher molecular weights as well as an increase in mean molecular weight. Reaction mechanisms are considered, and results of spectrographic analysis are cited which support the interpretations of the molecular-weight data.

  4. Composition and molecular weight distribution of carob germ protein fractions.

    PubMed

    Smith, Brennan M; Bean, Scott R; Schober, Tilman J; Tilley, Michael; Herald, Thomas J; Aramouni, Fadi

    2010-07-14

    Biochemical properties of carob germ proteins were analyzed using a combination of selective extraction, reversed-phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC) coupled with multiangle laser light scattering (SEC-MALS), and electrophoretic analysis. Using a modified Osborne extraction procedure, carob germ flour proteins were found to contain approximately 32% albumin and globulin and approximately 68% glutelin with no prolamins detected. The albumin and globulin fraction was found to contain low amounts of disulfide-bonded polymers with relatively low M(w) ranging up to 5 x 10(6) Da. The glutelin fraction, however, was found to contain large amounts of high molecular weight disulfide-bonded polymers with M(w) up to 8 x 10(7) Da. When extracted under nonreducing conditions and divided into soluble and insoluble proteins as typically done for wheat gluten, carob germ proteins were found to be almost entirely ( approximately 95%) in the soluble fraction with only ( approximately 5%) in the insoluble fraction. As in wheat, SEC-MALS analysis showed that the insoluble proteins had a greater M(w) than the soluble proteins and ranged up to 8 x 10(7) Da. The lower M(w) distribution of the polymeric proteins of carob germ flour may account for differences in functionality between wheat and carob germ flour.

  5. Preparation and hemostatic property of low molecular weight silk fibroin.

    PubMed

    Lei, Caihong; Zhu, Hailin; Li, Jingjing; Feng, Xinxing; Chen, Jianyong

    2016-01-01

    Effective hemorrhage control becomes increasingly significant in today's military and civilian trauma, while the topical hemostats currently available in market still have various disadvantages. In this study, three low molecular weight silk fibroins (LMSF) were prepared through hydrolysis of silk fibroin in a ternary solvent system of CaCl2/H2O/EtOH solution at different hydrolysis temperatures. Fourier transform infrared spectroscopy analysis showed that the content of β sheet structure in the LMSF decreased with the increase in hydrolysis temperature. The results of thromboelastographic and activated partial thromboplastin time methods showed that the LMSF hydrolyzed at 50 °C can significantly strengthen the coagulation in blood and activate the intrinsic pathway of coagulation cascade. In the murine hepatic injury model, the LMSF hydrolyzed at 50 °C can promote the blood clotting and decrease the blood loss and bleeding time. Based on these results, it can be suggested that the developed LMSF has the excellent hemostatic effect and may be a promising material in clinical hemostatic application.

  6. Adsorption of low molecular weight halocarbons by montmorillonite

    SciTech Connect

    Estes, T.J.; Shah, R.V.; Vilker, V.L. )

    1988-04-01

    Montmorillonite clay from Clay Spur, WY, was found to adsorb several low molecular weight, hydrophobic halocarbons from aqueous solution at sub-parts-per-million levels. The halocarbons studied were trichloroethylene, tetrachloroethylene, hexachloroethane, and dibromochloropropane. When the montmorillonite was treated with sodium citrate-bicarbonate-dithionite (CBD), it adsorbed higher levels of halocarbons than the untreated clay. In addition, the CBD-treated clay exhibited a maximum in halocarbon adsorption around pH 4, while untreated clay showed little variation in adsorption over the pH range 2-10. Adsorption of trichloroethylene was inhibited by low concentrations of sodium chloride (0.01 M or greater) in solution. Aging the CBD-treated clay in water decreased its capacity to adsorb trichloroethylene. Desorption studies showed that the sorption of tetrachloroethylene to CBD-treated clay is an irreversible process when compared to sorption by fumed silica. The ability of montmorillonite to adsorb halocarbons and the instability of the clay in water are postulated to involve changes in the oxide surface coating on the clay.

  7. Antiaging activity of low molecular weight peptide from Paphia undulate

    NASA Astrophysics Data System (ADS)

    Chen, Xin; Cai, Bingna; Chen, Hua; Pan, Jianyu; Chen, Deke; Sun, Huili

    2013-05-01

    Low molecular weight peptide (LMWP) was prepared from clam Paphia undulate and its antiaging effect on D-galactose-induced acute aging in rats, aged Kunming mice, ultraviolet-exposed rats, and thermally injured rats was investigated. P. undulate flesh was homogenized and digested using papain under optimal conditions, then subjected to Sephadex G-25 chromatography to isolate the LMWP. Administration of LMWP significantly reversed D-galactose-induced oxidative stress by increasing the activities of glutathione peroxidase (GPx) and catalase (CAT), and by decreasing the level of malondialdehyde (MDA). This process was accompanied by increased collagen synthesis. The LMWP prevented photoaging and promoted dermis recovery and remission of elastic fiber hyperplasia. Furthermore, treatment with the LMWP helped to regenerate elastic fibers and the collagen network, increased superoxide dismutase (SOD) in the serum and significantly decreased MDA. Thermal scald-induced inflammation and edema were also relieved by the LWMP, while wound healing in skin was promoted. These results suggest that the LMWP from P. undulate could serve as a new antiaging substance in cosmetics.

  8. Method for determination of polyethylene glycol molecular weight.

    PubMed

    Pihlasalo, Sari; Hänninen, Pekka; Härmä, Harri

    2015-04-07

    A method utilizing competitive adsorption between polyethylene glycols (PEGs) and labeled protein to nanoparticles was developed for the determination of PEG molecular weight (MW) in a microtiter plate format. Two mix-and-measure systems, time-resolved luminescence resonance energy transfer (TR-LRET) with donor europium(III) polystyrene nanoparticles and acceptor-labeled protein and quenching with quencher gold nanoparticles and fluorescently labeled protein were compared for their performance. MW is estimated from the PEG MW dependent changes in the competitive adsorption properties, which are presented as the luminescence signal vs PEG mass concentration. The curves obtained with the TR-LRET system overlapped for PEGs larger than 400 g/mol providing no information on MW. Distinctly different curves were obtained with the quenching system enabling the assessment of PEG MW within a broad dynamic range. The data was processed with and without prior knowledge of the PEG concentration to measure PEGs over a MW range from 62 to 35,000 g/mol. The demonstration of the measurement independent of the PEG concentration suggests that the estimation of MW is possible with quenching nanoparticle system for neutrally charged and relatively hydrophilic polymeric molecules widening the applicability of the simple and cost-effective nanoparticle-based methods.

  9. Biocompatibility of modified ultra-high-molecular-weight polyethylene

    NASA Astrophysics Data System (ADS)

    Novotná, Z.; Lacmanová, V.; Rimpelová, S.; Juřik, P.; Polívková, M.; Å vorčik, V.

    2016-09-01

    Ultra-high-molecular-weight polyethylene (UHMWPE, PE) is a synthetic polymer used for biomedical applications because of its high impact resistance, ductility and stability in contact with physiological fluids. Therefore this material is being used in human orthopedic implants such as total joint replacements. Surface modification of this material relates to changes of its surface hydrophilicity, energy, microstructure, roughness, and morphology, all influencing its biological response. In our recent work, PE was treated by an Ar+ plasma discharge and then grafted with biologically active polyethylene glycol in order to enhance adhesion and proliferation of mouse fibroblast (L929). The surface properties of pristine PE and its grafted counterparts were studied by goniometry (surface wettability). Furthermore, Atomic Force Microscopy was used to determine the surface morphology and roughness. The biological response of the L929 cell lines seeded on untreated and plasma treated PE matrices was quantified in terms of the cell adhesion, density, and metabolic activity. Plasma treatment leads to the ablation of the polymer surface layers. Plasma treatment and subsequent poly(ethylene glycol) grafting lead to dramatic changes in the polymer surface morphology and roughness. Biological tests, performed in vitro, show increased adhesion and proliferation of cells on modified polymers. Grafting with poly(ethylene glycol) increases cell proliferation compared to plasma treatment.

  10. The Effect of Low Molecular Weight Heparins on Fracture Healing

    PubMed Central

    Kapetanakis, Stylianos; Nastoulis, Evangelos; Demesticha, Theano; Demetriou, Thespis

    2015-01-01

    Venous Thromboembolism is a serious complication in the trauma patient. The most commonly studied and used anticoagulant treatment in prophylaxis of thrombosis is heparin. The prolonged use of unfractionated heparin has been connected with increased incidence of osteoporotic fractures. Low molecular-weight-heparins (LMWHs) have been the golden rule in antithrombotic therapy during the previous two decades as a way to overcome the major drawbacks of unfractioned heparin. However there are few studies reporting the effects of LMWHs on bone repair after fractures. This review presents the studies about the effects of LMWHs on bone biology (bone cells and bone metabolism) and underlying the mechanisms by which LMWHs may impair fracture healing process. The authors’ research based on literature concluded that there are no facts and statistics for the role of LMWHs on fracture healing process in humans and the main body of evidence of their role comes from in vitro and animal studies. Further large clinical studies designed to compare different types of LMWHs, in different dosages and in different patient or animal models are needed for exploring the effects of LMWHs on fracture healing process. PMID:26161162

  11. Can we differentiate the low-molecular-weight heparins?

    PubMed

    Turpie, A G

    2000-01-01

    The low-molecular-weight heparins (LMWHs) have a number of therapeutic advantages, relative to standard unfractionated heparin (UFH). They are readily bioavailable when injected subcutaneously and can be given in fixed doses, allowing for far simpler administration. Several LMWHs are now commercially available, each demonstrating different physical and chemical properties and different activities in animal models of anticoagulation or hemorrhage. In clinical comparisons with placebo in the treatment of unstable coronary artery disease (UCAD), the LMWHs dalteparin sodium and nadroparin calcium have demonstrated good anticoagulant efficacy. In comparisons with UFH, on the other hand, only enoxaparin has shown superior anticoagulant activity, as reported in the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI) 11B trials. However, close scrutiny of the methodology of the clinical trials in UCAD reveals considerable differences in study designs, dosage regimens, duration of administration of active treatments, and the timing and definition of endpoints. Therefore, it would not be scientifically sound to compare results with the different LMWHs based on the current available studies. It is also not possible to draw any conclusions with regard to the relative efficacy of the different LMWHs, since there are no properly-sized comparative data between dalteparin sodium, enoxaparin sodium, and nadroparin calcium.

  12. Low molecular weight heparin use in unexplained recurrent miscarriage

    PubMed Central

    Yuksel, Halide; Kayatas, Semra; Boza, Aysen Telce; Api, Murat; Ertekin, A. Aktug; Cam, Cetin

    2014-01-01

    Objective: The aim of the study was to investigate whether the use of low molecular weight heparin (LMWH) improve live birth rates when compared with control group in patients with unexplained recurrent miscarriages (URM). Methods: In this prospective observational study 150 women with a history of two or more previous unexplained first trimester pregnancy loss who received LMWH; either enoxaparin (n=50), tinzaparin (n=50) or nothing (n=50) were followed for the pregnancy outcome measures. Only the patients who have used standardized dosage of LMWH (4000 IU/day enoxaparin or 3500 IU/day tinzaparin ) were included to the study. The primary end point was the live birth rate and secondary end points were the side effects, late pregnancy complications and neonatal outcome in the study cohorts. Results: Live birth was achieved 85% of the LMWH group and 66% of the control group (p=0.007). According to the subgroup analysis; live birth rates did not differ significantly between the enoxaparin and tinzaparin group (84% and 86%, respectively). Maternal and neonatal side effects were not statistically significant among the study participants. Conclusion: Thromboprophylaxis with LMWH resulted in a improved live-birth rate in patient with 2 or more consecutive unexplained recurrent pregnancy loss. Nevertheless these findings need to be confirmed in larger randomized trials. PMID:25674114

  13. Delamination toughness of ultra high molecular weight polyethylene (UHMWPE) composites

    NASA Astrophysics Data System (ADS)

    Porras, A.; Tellez, J.; Casas-Rodriguez, J. P.

    2012-08-01

    Ultra high molecular weight polyethylene (UHMWPE) fibre reinforced composites are an important group of material for armours solutions, where their unique combination of properties could be utilized. A commonly observed failure mode in this kind of unidirectional laminated composites under impact ballistic is delamination between the composite layers. In the present study, an investigation on the delamination toughness behaviour exhibited by UHMWPE composites laminated was made. The interlaminar Mode II critical strain energy release rates of (UHMWPE) fibre reinforced composites were characterized using the End Notch Flexural (ENF) test. Critical strain energy release rate was obtained from the load - deflection test data using the beam theory expression. It was found that the energy release rate of the composite exhibited a very low value of around 60J/m2 using a moulding pressure of approximately 1200 psi. In order to analyse the delamination resistance of composite, the effects of changing the manufacture process variables and the use of a thermoplastic adhesive film in the composites were investigated. The composite laminates were produced by hot compressing moulding using a film-stacking procedure. It was found that the damage resistance of the UHMWPE composite was influenced by the manufacture method, which affects the Mode II interlaminar fracture toughness and the ballistic response of composites.

  14. Using low molecular weight heparin in special patient populations.

    PubMed

    Lim, Wendy

    2010-02-01

    Clinical trials evaluating low molecular weight heparin (LMWH) for the prevention and treatment of venous thromboembolism and acute coronary syndromes have led to their regulatory approval for these indications in the general population. However, certain patient populations have been excluded from these landmark clinical trials, including patients with renal insufficiency, obese patients and pregnant women. In these special populations, data on safety and efficacy is limited and typically based on pharmacokinetic studies often performed in healthy subjects, or small cohort studies which are generally not powered to evaluate clinical outcomes such as bleeding or recurrent thrombosis. Because LMWH is mainly cleared renally, patients with severe renal insufficiency are at risk of LMWH accumulation and increased bleeding risks. In obese patients, there is concern regarding possible overdosing of therapeutic dose LMWH, since LMWH does not distribute in fat tissue. There are also concerns about possible underdosing of prophylactic dose LMWH in obese individuals using the standard fixed doses, particularly in the extremely obese individuals undergoing bariatric surgery. Last, pregnancy poses challenges with regards to the safety of LMWH during pregnancy and use of LMWH around delivery. This review summarizes the existing data in these special populations and proposes general recommendations for practice.

  15. Fatigue crack propagation behavior of ultrahigh molecular weight polyethylene.

    PubMed

    Connelly, G M; Rimnac, C M; Wright, T M; Hertzberg, R W; Manson, J A

    1984-01-01

    The relative fatigue crack propagation resistance of plain and carbon fiber-reinforced ultrahigh molecular weight polyethylene (UHMWPE) was determined from cyclic loading tests performed on compact tension specimens machined from the tibial components of total knee prostheses. Both materials were characterized by dynamic mechanical spectroscopy, X-ray diffraction, and differential scanning calorimetry. The cyclic tests used loading in laboratory air at 5 Hz using a sinusoidal wave form. Dynamic mechanical spectroscopy showed that the reinforced UHMWPE had a higher elastic storage modulus than the plain UHMWPE, whereas X-ray diffraction and differential scanning calorimetry showed that the percent crystallinity and degree of order in the crystalline regions were similar for the two materials. Fatigue crack propagation in both materials proved to be very sensitive to small changes in the applied cyclic stress intensity range. A 10% increase in stress intensity resulted in approximately an order of magnitude increase in fatigue crack growth rate. The fatigue crack propagation resistance of the reinforced UHMWPE was found to be significantly worse than that of the plain UHMWPE. This result was attributed to poor bonding between the carbon fibers and the UHMWPE matrix and the ductile nature of the matrix itself.

  16. Regulatory considerations for generic or biosimilar low molecular weight heparins.

    PubMed

    García-Arieta, Alfredo; Blázquez, Antonio

    2012-06-01

    The aim of the present paper is to address the legal aspects, technical requirements and possible conditions of use associated to low molecular weight heparin generics and biosimilars that are arriving to the market in United States and the European Union, respectively. To this end the concept of "similar biological medicinal product" that was coined in 2003 by the pharmaceutical legislation of the European Union is compared to the concept of generic in the United States and the concept of generic in the European Union. This different legal basis determines directly the technical requirements to obtain a marketing authorisation. Therefore, the chemical/biological, non-clinical and clinical requirements to demonstrate therapeutic equivalence are different in these two Regulatory Authorities, FDA and EMA. Consequently, the possible conditions of use are different. In the United States the products approved as generics by the FDA are considered interchangeable to the Reference Listed Drug. In contrast, the EMA legislation only deals with the approvability or prescribability of the medicines and it is a national / regional decision of the member States to consider these biosimilar products as interchangeable or not.

  17. Ultra High Molecular Weight Polyethylene: Mechanics, Morphology, and Clinical Behavior

    PubMed Central

    Sobieraj, MC; Rimnac, CM

    2013-01-01

    Ultra high molecular weight polyethylene (UHMWPE) is a semicrystalline polymer that has been used for over four decades as a bearing surface in total joint replacements. The mechanical properties and wear properties of UHMWPE are of interest with respect to the in vivo performance of UHMWPE joint replacement components. The mechanical properties of the polymer are dependent on both its crystalline and amorphous phases. Altering either phase (i.e., changing overall crystallinity, crystalline morphology, or crosslinking the amorphous phase) can affect the mechanical behavior of the material. There is also evidence that the morphology of UHMWPE, and, hence, its mechanical properties evolve with loading. UHMWPE has also been shown to be susceptible to oxidative degradation following gamma radiation sterilization with subsequent loss of mechanical properties. Contemporary UHMWPE sterilization methods have been developed to reduce or eliminate oxidative degradation. Also, crosslinking of UHMWPE has been pursued to improve the wear resistance of UHMWPE joint components. The 1st generation of highly crosslinked UHMWPEs have resulted in clinically reduced wear; however, the mechanical properties of these materials, such as ductility and fracture toughness, are reduced when compared to the virgin material. Therefore, a 2nd generation of highly crosslinked UHMWPEs are being introduced to preserve the wear resistance of the 1st generation while also seeking to provide oxidative stability and improved mechanical properties. PMID:19627849

  18. Low molecular weight protamine (LMWP) as nontoxic heparin/low molecular weight heparin antidote (I): preparation and characterization.

    PubMed

    Chang, L C; Lee, H F; Yang, Z; Yang, V C

    2001-01-01

    Low molecular weight protamine (LMWP) appears to be a promising solution for heparin neutralization without the protamine-associated catastrophic toxic effects. The feasibility of this hypothesis was proven previously by using a peptide mixture produced from proteolytic digestion of protamine. To further examine the utility of this compound as an ultimate nontoxic protamine substitute, detailed studies on the purification and characterization of LMWP including the precise amino acid sequence, structure-function relationship, and possible mechanism were conducted. A number of LWMP fragments, composed of highly cationic peptides with molecular weights ranging from 700 to 1900 d, were prepared by digestion of native protamine with the protease thermolysin. These fragments were fractionated using a heparin affinity chromatography, and their relative binding strengths toward heparin were elucidated. Five distinct fractions were eluted at NaCl concentration ranging from 0.4 to 1.0 M and were denoted as TDSP1 to TDSP5, in increasing order of eluting ionic strength. Among these 5 fractions, TDSP4 and TDSP5 contained 3 LMWP peptide fragments, and they were found to retain the complete heparin-neutralizing function of protamine. By using a peptide mass spectrometry (MS) fingerprint mapping technique, the amino acid sequences of the microheterogeneous LMWP fragments in all these 5 elution fractions were readily identified. A typical structural scaffold made by arginine clusters in the middle and nonarginine residues at the N-terminal of the peptide sequence was observed for all these LMWP fragments. By aligning the sequences with the potency in heparin neutralization of these LMWP fragments, it was found that retention of potency similar to that of protamine required the presence of at least 2 arginine clusters in the LMWP fragments; such as the sequence of VSRRRRRRGGRRRR seen in the most potent LMWP fraction-TDSP5. The above finding was further validated by using a synthetic

  19. Chromatographic molecular weight measurements for heparin, its fragments and fractions, and other glycosaminoglycans.

    PubMed

    Mulloy, Barbara; Hogwood, John

    2015-01-01

    Glycosaminoglycan samples are usually polydisperse, consisting of molecules with differing length and differing sequence. Methods for measuring the molecular weight of heparin have been developed to assure the quality and consistency of heparin products for medicinal use, and these methods can be applied in other laboratory contexts. In the method described here, high-performance gel permeation chromatography is calibrated using appropriate heparin molecular weight markers or a single broad standard calibrant, and used to characterize the molecular weight distribution of polydisperse samples or the peak molecular weight of monodisperse, or approximately monodisperse, heparin fractions. The same technology can be adapted for use with other glycosaminoglycans.

  20. Degradation mechanisms of bioresorbable polyesters. Part 2. Effects of initial molecular weight and residual monomer.

    PubMed

    Gleadall, Andrew; Pan, Jingzhe; Kruft, Marc-Anton; Kellomäki, Minna

    2014-05-01

    This paper presents an understanding of how initial molecular weight and initial monomer fraction affect the degradation of bioresorbable polymers in terms of the underlying hydrolysis mechanisms. A mathematical model was used to analyse the effects of initial molecular weight for various hydrolysis mechanisms including noncatalytic random scission, autocatalytic random scission, noncatalytic end scission or autocatalytic end scission. Different behaviours were identified to relate initial molecular weight to the molecular weight half-life and to the time until the onset of mass loss. The behaviours were validated by fitting the model to experimental data for molecular weight reduction and mass loss of samples with different initial molecular weights. Several publications that consider initial molecular weight were reviewed. The effect of residual monomer on degradation was also analysed, and shown to accelerate the reduction of molecular weight and mass loss. An inverse square root law relationship was found between molecular weight half-life and initial monomer fraction for autocatalytic hydrolysis. The relationship was tested by fitting the model to experimental data with various residual monomer contents.

  1. Mechanistic aspects of the low-molecular-weight phosphatase activity of the calmodulin-activated phosphatase, calcineurin.

    PubMed

    Martin, B L; Graves, D J

    1986-11-05

    Product and substrate analogs have been employed as inhibitors of the low-molecular-weight phosphatase activity of calcineurin, a calmodulin-activated protein phosphatase. Product inhibition kinetics demonstrate that both products, para-nitrophenol and inorganic phosphate, inhibit para-nitrophenyl phosphate hydrolysis in a competitive manner. Inorganic phosphate is a linear competitive inhibitor, whereas the inhibition by para-nitrophenol is more complex. An analog of para-nitrophenol, pentafluorophenol, was found to be a linear competitive inhibitor. These patterns indicate a rapid equilibrium random kinetic mechanism for calcineurin. This mechanism suggests that calcineurin does not generate a phosphoryl enzyme during its catalytic reaction. Application of sulfate analogs indicates that binding of substrate occurs via the phosphoryl moiety. It is suggested that binding is a function of the affinity of ligand for the metal ion involved in calcineurin action. The dependence of the kinetic parameters of calcineurin upon pH was examined to provide information concerning the role of protonation in the activity and specificity of calcineurin. Log (VM) versus pH data for two low-molecular-weight substrates, para-nitrophenyl phosphate and tyrosine-O-phosphate, reveal a pKa value for the enzyme-substrate complex. Analysis of log (VM/KM) data yields a pKa value for the free enzyme of 8.0. Protonation of the phenolic leaving group during hydrolysis is not the rate-limiting step in calcineurin catalysis.

  2. Effect of cross-linking ultrahigh molecular weight polyethylene: Surface molecular orientation and wear characteristics

    SciTech Connect

    Sambasivan, Sharadha; Fischer, Daniel A.; Hsu, Stephen M.

    2007-07-15

    Molecular orientation at the surface layer of cross-linked ultrahigh molecular weight polyethylene (UHMWPE) has been examined. Molecular orientation has been shown to affect the wear resistance and surface mechanical properties of UHMWPE under biomechanical loading conditions. This study utilizes a nondestructive synchrotron based soft x-ray technique; near edge x-ray absorption fine structure at the carbon K-edge to examine the degree of surface molecular orientation of UHMWPE subjected to various cross-linking/sterilization techniques as a function of stress and wear. UHMWPE samples prepared under gamma irradiation, ethylene-oxide (EtO) treatment, and electron beam irradiation were worn in a wear tester systematically. Results suggest that the cross-linking resists surface orientation when the samples were under tensile and biomechanical stresses. The molecular orientation in the C-C chains in the polymer showed a monotonic decrease with an increase in gamma irradiation dosage levels. EtO sterilized samples showed more C-C chain orientation than the electron beam irradiated samples, but lower than the 30 kGy gamma irradiated samples. Ordered C-C chains in UHMWPE samples have been associated with more crystallinity or large strain plastic deformation of the polymer. Higher levels of gamma irradiation appear to induce cross-linking of C-C chains and render a polymer with more amorphous phase which resists orientation after wear and imparts wear resistance to the polymer.

  3. Molecular weight effects on interfacial properties of linear and ring polymer melts: A molecular dynamics study

    NASA Astrophysics Data System (ADS)

    Meddah, Chahrazed; Milchev, Andrey; Sabeur, Sid Ahmed; Skvortsov, Alexander M.

    2016-11-01

    Using molecular dynamics simulations, we study and compare the pressure, P, and the surface tension, γ , of linear chains and of ring polymers at the hard walls confining both melts into a slit. We examine the dependence of P and γ on the length (i.e., molecular weight) N of the macromolecules. For linear chains, we find that both pressure and surface tension are inversely proportional to the chain length, P (N ) -P (N →∞ ) ∝N-1,γ (N ) -γ (N →∞ ) ∝N-1 , irrespective of whether the confining planes attract or repel the monomers. In contrast, for melts comprised of cyclic (ring) polymers, neither the pressure nor the surface tension is found to depend on molecular weight N for both kinds of wall-monomer interactions. While other structural properties as, e.g., the probability distributions of trains and loops at impenetrable walls appear quantitatively indistinguishable, we observe an amazing dissimilarity in the probability to find a chain end or a tagged monomer of a ring at a given distance from the wall in both kinds of polymeric melts. In particular, we demonstrate that the conformational equivalence of linear chains in a confined melt to a single chain under conditions of critical adsorption to a planar surface, established two decades ago, does also hold for ring polymers in a melt of linear chains. This analogy does not hold, however, for linear and ring chains in a confined melt of ring chains.

  4. Purification of a Low Molecular Weight Fucoidan for SPECT Molecular Imaging of Myocardial Infarction

    PubMed Central

    Saboural, Pierre; Chaubet, Frédéric; Rouzet, Francois; Al-Shoukr, Faisal; Ben Azzouna, Rana; Bouchemal, Nadia; Picton, Luc; Louedec, Liliane; Maire, Murielle; Rolland, Lydia; Potier, Guy; Le Guludec, Dominique; Letourneur, Didier; Chauvierre, Cédric

    2014-01-01

    Fucoidans constitute a large family of sulfated polysaccharides with several biochemical properties. A commercial fucoidan from brown algae, containing low molecular weight polysaccharidic species constituted of l-fucose, uronic acids and sulfate groups, was simply treated here with calcium acetate solution. This treatment led to a purified fraction with a yield of 45%. The physicochemical characterizations of the purified fucoidan using colorimetric assay, MALLS, dRI, FT-IR, NMR, exhibited molecular weight distributions and chemical profiles similar for both fucoidans whereas the sulfate and l-fucose contents increased by 16% and 71%, respectively. The biodistribution study in rat of both compounds labeled with 99mTc evidenced a predominant renal elimination of the purified fucoidan, but the crude fucoidan was mainly retained in liver and spleen. In rat myocardial ischemia-reperfusion, we then demonstrated the better efficiency of the purified fucoidan. This purified sulfated polysaccharide appears promising for the development of molecular imaging in acute coronary syndrome. PMID:25251032

  5. Molecular imprinted polymer-coated optical fiber sensor for the identification of low molecular weight molecules.

    PubMed

    Lépinay, Sandrine; Ianoul, Anatoli; Albert, Jacques

    2014-10-01

    A biomimetic optical probe for detecting low molecular weight molecules (maltol, 3-hydroxy-2-methyl-4H-pyran-4-one, molecular weight of 126.11 g/mol), was designed, fabricated, and characterized. The sensor couples a molecular imprinted polymer (MIP) and the Bragg grating refractometry technology into an optical fiber. The probe is fabricated first by inscribing tilted grating planes in the core of the fiber, and then by photopolymerization to immobilize a maltol imprinted MIP on the fiber cladding surface over the Bragg grating. The sensor response to the presence of maltol in different media is obtained by spectral interrogation of the fiber transmission signal. The results showed that the limit of detection of the sensor reached 1 ng/mL in pure water with a sensitivity of 6.3 × 10(8)pm/M. The selectivity of the sensor against other compounds and its reusability were also studied experimentally. Finally, the unambiguous detection of concentrations as little as 10nM of maltol in complex media (real food samples) by the MIP-coated tilted fiber Bragg grating sensor was demonstrated.

  6. Feasibility of using molecular docking-based virtual screening for searching dual target kinase inhibitors.

    PubMed

    Zhou, Shunye; Li, Youyong; Hou, Tingjun

    2013-04-22

    Multitarget agents have been extensively explored for solving limited efficacies, poor safety, and resistant profiles of an individual target. Theoretical approaches for searching and designing multitarget agents are critically useful. Here, the performance of molecular docking to search dual-target inhibitors for four kinase pairs (CDK2-GSK3B, EGFR-Src, Lck-Src, and Lck-VEGFR2) was assessed. First, the representative structures for each kinase target were chosen by structural clustering of available crystal structures. Next, the performance of molecular docking to distinguish inhibitors from noninhibitors for each individual kinase target was evaluated. The results show that molecular docking-based virtual screening illustrates good capability to find known inhibitors for individual targets, but the prediction accuracy is structurally dependent. Finally, the performance of molecular docking to identify the dual-target kinase inhibitors for four kinase pairs was evaluated. The analyses show that molecular docking successfully filters out most noninhibitors and achieves promising performance for identifying dual-kinase inhibitors for CDK2-GSK3B and Lck-VEGFR2. But a high false-positive rate leads to low enrichment of true dual-target inhibitors in the final list. This study suggests that molecular docking serves as a useful tool in searching inhibitors against dual or even multiple kinase targets, but integration with other virtual screening tools is necessary for achieving better predictions.

  7. [Low molecular weight heparin and non valvular atrial fibrillation].

    PubMed

    Ederhy, S; Di Angelantonio, E; Meuleman, C; Janower, S; Boccara, F; Cohen, A

    2006-12-01

    Low molecular weight heparin (LMWH) are obtained through chemical or enzyme depolymerisation of unfractioned heparins (UFH). LMWHs present several advantages over UFH: they exhibit a smaller interindividual variability of the anticoagulant effect, they have a greater bioavailability, a longer plasma half-life and do not require monitoring of the anticoagulant effect. LMWH have restrictive indications in AF patients, cardioversion (II level C and TEE for ACC/AHA/ESC and 2C for ACCP guidelines) or use as a bridge therapy (IIB, level C for ACC/AHA/ESC). The ACE study (Anticoagulation for cardioversion using enoxaparin), showed a reduction, though not statistically significant, of 42% of the composite end point (embolic event, major bleeding and death) 2.8% under enoxaparin vs. 4.8 % under conventional treatment, relative risk 0.58, CI 95% 0.23-1.46). Other studies, using dalteparin, confirmed that an anticoagulant treatment using LMWH followed by warfarin was at least as good as conventional management. ACUTE II (Assessment of cardioversion using transesophageal echochardiography), a randomized multicenter trial, compared the efficacy and tolerance of enoxaparin (1 mg/kg every 12 hours) and UFH in 155 patients eligible for a TEE-guided cardioversion. These patients were administered LMWH or UFH for 24 hours before TEE or cardioversion. There were no significative differences regarding the incidence of the study end points, in particular stroke and bleeding, and no death occurred. HAEST (Heparin in acute embolic stroke trial), a randomized, placebo-controlled, double blind trial failed to show the LMWH superiority over aspirin in patients with acute ischemic stroke and atrial fibrillation. Finally, LMWH have been proposed as a bridge therapy in patients under chronic VKA prior to surgery or invasive procedures. This strategy resulted in a low rate of thromboembolic events and major bleedings.

  8. High Molecular Weight Petrogenic and Pyrogenic Hydrocarbons in Aquatic Environments

    NASA Astrophysics Data System (ADS)

    Abrajano, T. A., Jr.; Yan, B.; O'Malley, V.

    2003-12-01

    Geochemistry is ultimately the study of sources, movement, and fate of chemicals in the geosphere at various spatial and temporal scales. Environmental organic geochemistry focuses such studies on organic compounds of toxicological and ecological concern (e.g., Schwarzenbach et al., 1993, 1998; Eganhouse, 1997). This field emphasizes not only those compounds with potential toxicological properties, but also the geological systems accessible to the biological receptors of those hazards. Hence, the examples presented in this chapter focus on hydrocarbons with known health and ecological concern in accessible shallow, primarily aquatic, environments.Modern society depends on oil for energy and a variety of other daily needs, with present mineral oil consumption throughout the 1990s exceeding 3×109 t yr-1 (NRC, 2002). In the USA, e.g., ˜40% of energy consumed and 97% of transportation fuels are derived from oil. In the process of extraction, refinement, transport, use, and waste production, a small but environmentally significant fraction of raw oil materials, processed products, and waste are released inadvertently or purposefully into the environment. Because their presence and concentration in the shallow environments are often the result of human activities, these organic materials are generally referred to as "environmental contaminants." Although such reference connotes some form of toxicological or ecological hazard, specific health or ecological effects of many organic "environmental contaminants" remain to be demonstrated. Some are, in fact, likely innocuous at the levels that they are found in many systems, and simply adds to the milieu of biogenic organic compounds that naturally cycle through the shallow environment. Indeed, virtually all compounds in crude oil and processed petroleum products have been introduced naturally to the shallow environments as oil and gas seepage for millions of years ( NRC, 2002). Even high molecular weight (HMW) polyaromatic

  9. Characterization and analysis of the molecular weight of lignin for biorefining studies

    SciTech Connect

    Tolbert, Allison; Akinosho, Hannah; Khunsupat, Ratayakorn; Naskar, Amit K.; Ragauskas, Arthur J.

    2014-06-04

    The molecular weight of lignin is a fundamental property that infl uences the recalcitrance of biomass and the valorization of lignin. The determination of the molecular weight of lignin in native biomass is dependent on the bioresources used and the isolation and purifi cation procedures employed. The three most commonly employed isolation methods are milled wood lignin (MWL), cellulolytic enzyme lignin (CEL), and enzymatic mild acidolysis lignin (EMAL). Common characterization techniques for determining the molecular weight of lignin will be addressed, with an emphasis on gel permeation chromatography (GPC). This review also examines the mechanisms behind several biological, physical, and chemical pre-treatments and their impact on the molecular weight of lignin. The number average molecular weight (Mn), weight average molecular weight (Mw) and polydispersity index (D) all vary in magnitude depending on the biomass source, pre-treatment conditions, and isolation method. Additionally, there is a growing body of literature that supports changes in the molecular weight of lignin in response to genetic modifi cations in the lignin biosynthetic pathways. This review summarizes different procedures for obtaining the molecular weight of lignin that have been used in recent years and highlight future opportunities for applications of lignin.

  10. Molecular dynamics study of the molecular weight dependence of surface tensions of normal alkanes and methyl methacrylate oligomers.

    PubMed

    Li, Chunli; Choi, Phillip

    2006-04-06

    Surface tensions (gamma) of normal alkanes and methyl methacrylate (MMA) oligomers at various molecular weights in the low molecular weight range were computed using a newly proposed molecular dynamics (MD) simulation strategy which was developed based on the definition of gamma = ( partial differential U/ partial differential sigma)n,V,S. The MD simulations, even with the use of a generic force field, reproduced the experimentally observed molecular weight dependence of gamma (i.e., gamma proportional Mn(-2/3), where Mn is the number-average molecular weight) for both series of oligomers. Analysis of the data reveals that solvent accessible surface area, one of the key input variables used for the calculation of gamma, exhibits an Mn(2/3) (rather than Mn(1)) dependence. The reason for such dependence is that solvent accessible surface area formed by the chainlike small molecules depends, to a larger extent, on their orientations rather than their size. However, this is not the case for high molecular weight molecules as solvent accessible surface area of such surfaces are determined by the orientations of their segments which are determined by the conformations of the molecules. This may explain why surface tension of polymers experimentally exhibits an Mn(-1) dependence. It is inferred that the corresponding molecular weight dependence of the entropy changes associated with molecules in the low and high molecular weight ranges would be different.

  11. High molecular weight insulating polymers can improve the performance of molecular solar cells

    NASA Astrophysics Data System (ADS)

    Huang, Ye; Wen, Wen; Kramer, Edward; Bazan, Guillermo

    2014-03-01

    Solution-processed molecular semiconductors for the fabrication of solar cells have emerged as a competitive alternative to their conjugated polymer counterparts, primarily because such materials systems exhibit no batch-to-batch variability, can be purified to a greater extent and offer precisely defined chemical structures. Highest power conversion efficiencies (PCEs) have been achieved through a combination of molecular design and the application of processing methods that optimize the bulk heterojunction (BHJ) morphology. However, one finds that the methods used for controlling structural order, for example the use of high boiling point solvent additives, have been inspired by examination of the conjugated polymer literature. It stands to reason that a different class of morphology modifiers should be sought that address challenges unique to molecular films, including difficulties in obtaining thicker films and avoiding the dewetting of active photovoltaic layers. Here we show that the addition of small quantities of high molecular weight polystyrene (PS) is a very simple to use and economically viable additive that improves PCE. Remarkably, the PS spontaneously accumulates away from the electrodes as separate domains that do not interfere with charge extraction and collection or with the arrangement of the donor and acceptor domains in the BHJ blend.

  12. Molecular docking studies of a group of hydroxamate inhibitors with gelatinase-A by molecular dynamics

    NASA Astrophysics Data System (ADS)

    Hou, Tingjun; Zhang, Wei; Xu, Xiaojie

    2002-01-01

    We have performed docking and molecular dynamics simulations of hydroxamates complexed with human gelatinase-A (MMP-2) to gain insight into the structural and energetic preferences of these inhibitors. The study was conducted on a selected set of eleven compounds with variation in structure and activity. Molecular dynamics simulations were performed at 300 K for 100 ps with equilibration for 50 ps. The structural analyses of the trajectories indicate that the coordinate bond interactions, the hydrogen bond interactions, the van der Waals interactions as well as the hydrophobic interactions between ligand and receptor are responsible simultaneously for the preference of inhibition and potency. The ligand hydroxamate group is coordinated to the catalytic zinc ion and form stable hydrogen bonds with the carbonyl oxygen of Gly 162. The P1' group makes extensive van der Waals and hydrophobic contacts with the nonpolar side chains of several residues in the S1' subsite, including Leu 197, Val 198, Leu 218 and Tyr 223. Moreover, four to eight hydrogen bonds between hydroxamates and MMP-2 are formed to stabilize the inhibitors in the active site. Compared with the P2' and P3' groups, the P1' groups of inhibitors are oriented regularly, which is produced by the restrain of the S1' subsite. From the relationship between the length of the nonpolar P1' group and the biological activity, we confirm that MMP-2 has a pocket-like S1' subsite, not a channel-like S1' subsite proposed by Kiyama (Kiyama, R. et al., J. Med. Chem. 42 (1999), 1723). The energetic analyses show that the experimental binding free energies can be well correlated with the interactions between the inhibitors and their environments, which could be used as a simple score function to evaluate the binding affinities for other similar hydroxamates. The validity of the force field parameters and the MD simulations can be fully testified by the satisfactory agreements between the experimental structure

  13. Characterization of molecular recognition of STAT3 SH2 domain inhibitors through molecular simulation.

    PubMed

    Park, In-Hee; Li, Chenglong

    2011-01-01

    Signal transducer and activator of transcription 3 (STAT3) is an anti-cancer target protein due to its over-activation in tumor cells. The Tyr705-phosphorylated (pTyr) STAT3 binds to the pTyr-recognition site of its Src Homology 2 (SH2) domain of another STAT3 monomer to form a homo-dimer, which then causes cellular anti-apoptosis, proliferation, and tumor invasion. Recently, many STAT3 SH2 dimerization inhibitors have been discovered via both computational and experimental methods. To systematically assess their binding affinities and specificities, for eight representative inhibitors, we utilized molecular docking, molecular dynamics simulation, and ensuing energetic analysis to compare their binding characteristics. The inhibitors' binding free energies were calculated via MMPB(GB)SA, and the STAT3 SH2 binding "hot spots" were evaluated through binding energy decomposition and hydrogen bond (H-bond) distribution analysis. Several conclusions can be drawn: (1) the overall enthalpy-entropy compensation paradigm is preserved for the STAT3 SH2/ligand binding thermodynamics; (2) at one end of the binding spectrum, two compounds bind to SH2 due to their minimum entropic penalties that result from their relative rigidities and increased dynamics of SH2 upon their binding; at the other end of the binding spectrum, one compound shows a typical weak binder behavior due to its loose binding in the SH2's strongest enthalpy-contributing binding subsite; (3) hydrogen bonding seems a strong indicator to evaluate the SH2/ligand binding potency, which echoes a finding that CH/π non-classical H-bond is responsible for some pTyr peptides binding to their corresponding SH2 domains; (4) STAT3 SH2 domain possesses three binding "hot spots": pTyr705-binding pocket with polar residues and contributing the largest binding enthalpy (two-thirds); Leu706 subsite which is the most dynamic and hardest to target; a hydrophobic side pocket which is unique to STAT3 and very targetable, which

  14. Influence of polycation molecular weight on poly(2-dimethylaminoethyl methacrylate)-mediated DNA delivery in vitro.

    PubMed

    Layman, John M; Ramirez, Sean M; Green, Matthew D; Long, Timothy E

    2009-05-11

    Establishing clear structure-property-transfection relationships is a critical step in the development of clinically relevant polymers for nonviral gene therapy. In this study, we determined the influence of poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) molecular weight on cytotoxicity, DNA binding, and in vitro plasmid DNA delivery efficiency in human brain microvascular endothelial cells (HBMEC). Conventional free radical polymerization was used to synthesize PDMAEMA with weight-average molecular weights ranging from 43,000 to 915,000 g/mol. MTT and LDH assays revealed that lower molecular weight PDMAEMA (M(w) = 43,000 g/mol) was slightly less toxic than higher molecular weights (M(w) > 112,000 g/mol) and that the primary mode of toxicity was cellular membrane destabilization. An electrophoretic gel shift assay revealed that all PDMAEMA molecular weights completely bound with plasmid DNA. However, heparin competitive binding experiments revealed that higher molecular weight PDMAEMA (M(w) = 915,000 g/mol) had a greater binding affinity toward plasmid DNA than lower molecular weight PDMAEMA (M(w) = 43,000 g/mol). The molecular weight of PDMAEMA was found to have a dramatic influence on transfection efficiency, and luciferase reporter gene expression increased as a function of increasing molecular weight. However, cellular uptake of polyplexes was determined to be insensitive to PDMAEMA molecular weight. In addition, our data did not correlate polyplex size with transfection efficiency. Collectively, our data suggested that the intracellular fate of the polyplexes, which involves endosomal release and DNase resistance, is more important to overall transfection efficiency than barriers to entry, such as polyplex size.

  15. Molecular Weight Determination by an Improved Temperature-Monitored Vapor-Density Method.

    ERIC Educational Resources Information Center

    Grider, Douglas J.; And Others

    1988-01-01

    Recommends determining molecular weights of liquids by use of a thermocouple. Utilizing a mathematical gas equation, the molecular weight can be determined from the measurement of the vapor temperature upon complete evaporation. Lists benefits as reduced time and cost, and improved safety factors. (ML)

  16. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Polyethylene glycol (mean molecular weight 200-9... ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.820 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used in food...

  17. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  18. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polyethylene glycol (mean molecular weight 200-9... Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene... chapter. (c) The provisions of paragraph (b) of this section are not applicable to polyethylene...

  19. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  20. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Polyethylene glycol (mean molecular weight 200-9... ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.820 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used in food...

  1. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  2. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Polyethylene glycol (mean molecular weight 200-9... ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.820 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used in food...

  3. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polyethylene glycol (mean molecular weight 200-9... Multipurpose Additives § 172.820 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol... polyethylene glycol 400 shall be used to determine the total ethylene and diethylene glycol content...

  4. 21 CFR 172.820 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Polyethylene glycol (mean molecular weight 200-9... ADDITION TO FOOD FOR HUMAN CONSUMPTION Multipurpose Additives § 172.820 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used in food...

  5. 21 CFR 178.3750 - Polyethylene glycol (mean molecular weight 200-9,500).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Polyethylene glycol (mean molecular weight 200-9..., PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants and Production Aids § 178.3750 Polyethylene glycol (mean molecular weight 200-9,500). Polyethylene glycol identified in this section may be safely used as...

  6. Formation of high molecular weight products from benzene during boundary lubrication

    NASA Technical Reports Server (NTRS)

    Morales, W.

    1985-01-01

    High molecular weight products were detected on the wear track of an iron disk at the end of a sliding friction and wear test using benzene as a lubricant. Size exclusion chromagography in conjunction with UV analysis gave evidence that the high molecular weight products are polyphenyl ether type substances. Organic electrochemistry was used to elucidate the possible surface reaction mechanisms.

  7. Synthesis and self-assembly of 1-deoxyglucose derivatives as low molecular weight organogelators

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low molecular weight gelators are an important class of molecules. The supramolecular gels formed by carbohydrate derived low molecular weight gelators, are interesting soft materials that show great potential for many applications. Previously, we synthesized a series of methyl 4,6-O-benzylidene-a-D...

  8. A Simple, Inexpensive Molecular Weight Measurement for Water-Soluble Polymers Using Microemulsions.

    ERIC Educational Resources Information Center

    Mathias, Lon J.; Moore, D. Roger

    1985-01-01

    Describes an experiment involving use of a microemulsion and its characteristic thermal phase change to determine molecular weights of polyoxyethylene samples. The experiment provides students with background information on polymers and organized media and with experience in evaluating polymer molecular weight by using a unique property of a…

  9. The Relation Between Molecular Weight of Antigen and Ability to Elicit Passive Cutaneous Anaphylaxis*

    PubMed Central

    Leskowitz, S.; Ovary, Z.

    1962-01-01

    Passive cutaneous anaphylaxis in the guinea pig has been studied with rabbit antibody to a series of antigens of differing molecular weight. The results indicated that at a given antibody level the weight of antigen needed to elicit a reaction increases with its molecular weight. Previous observations have been confirmed that the amount of antigen needed to elicit a reaction at a high level of antibody is less than that required at a lower level. The results suggest that extremely small amounts of small molecular weight antigens might be sufficient to produce anaphylactic symptoms in highly sensitive individuals. PMID:14464304

  10. Bioremediation of Mixtures of High Molecular Weight Polycyclic Aromatic Hydrocarbons

    NASA Astrophysics Data System (ADS)

    Xu, H.; Wu, J.; Shi, X.; Sun, Y.

    2014-12-01

    Although bioremediation has been considered as one of the most promising means to remove polycyclic aromatic hydrocarbons (PAHs) from polluted environments, the efficacy of PAHs bioremediation still remains challenged, especially for high molecular weight PAHs (HMW PAHs) and their mixtures. This study was focused on (a) isolation and characterization of pure strain and mixed microbial communities able to degrade HMW PAHs and (b) further evaluation of the ability of the isolated microbes to degrade HMW PAHs mixtures in the absence and presence of indigenous flora. Fluoranthene, benzo[b]fluoranthene and pyrene were selected as the representative HMW PAHs in this study. A pure bacterial strain, identified as Herbaspirillum chlorophenolicum FA1, was isolated from activated sludge. A mixed bacterial community designated as consortium-4 was isolated from petroleum contaminated soils, containing Pseudomonas sp. FbP1、Enterobacter sp. FbP2、Hydrogenophaga sp. FbP3 and Luteolibacter pohnpeiensis. FbP4. To our knowledge, this is the first study to demonstrate that bacterial strains of Herbaspirillum chlorophenolicum FA1 and Luteolibacter pohnpeiensis. FbP4 can also degrade fluoranthene, benzo[b]fluoranthene and pyrene. Experiment results showed that both strain FA1 and consortium-4 could degrade fluoranthene, benzo[b]fluoranthene and pyrene within a wide range of temperature, pH and initial PAHs concentration. Degradation of HMW PAHs mixtures (binary and ternary) demonstrated the interactive effects that can alter the rate and extent of biodegradation within a mixture. The presence of indigenous flora was found to either increase or decrease the degradation of HMW PAHs, suggesting possible synergistic or competition effects. Biodegradation kinetics of HMW PAHs for sole substrates, binary and ternary systems was evaluated, with the purpose to better characterize and compare the biodegradation process of individual HMW PAH and mixtures of HMW PAHs. Results of this study

  11. Effects of a supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters.

    PubMed

    Glusa, E; Barthel, W; Schenk, J; Radziwon, P; Butti, A; Markwardt, F; Breddin, K H

    1998-01-01

    In a phase I trial effects of a new supersulfated low molecular weight heparin (IK-SSH) on different hemostatic parameters were investigated in healthy volunteers. Parameters studied were activated partial thromboplastin time (aPTT), thrombin time, Heptest, anti-activated factor II (anti-FIIa) and anti-activated factor X (anti-FXa) activity, platelet adhesion, platelet count, platelet-induced thrombin generation time (PITT), bleeding time, antithrombin III, fibrinogen and several safety parameters. After single intravenous (i.v.) injections of IK-SSH (0.14, 0.33 and 0.66 mg/kg) aPTT, Heptest and PITT were strongly and dose-dependently prolonged. After ascending subcutaneous (s.c.) doses of IK-SSH (0.33, 0.66 and 1 mg/kg) aPTT, Heptest and PITT were prolonged in a dose-dependent manner. Repeat s.c. injections of 1 mg/kg IK-SSH for 5 days markedly prolonged aPTT, Heptest and PITT. No cumulative effects were observed. Anti-FIIa and anti-FXa activity were not or only slightly increased. Bleeding time, thrombin time and platelet adhesion were not significantly changed after i.v. and s.c. injections of IK-SSH. However, tissue factor pathway inhibitor (TFPI) concentration was markedly increased after each injection of IK-SSH and returned to the preinjection value 24 h later. IK-SSH prolongs aPTT, Heptest and PITT in a similar manner as other low molecular weight heparins but without significantly affecting thrombin time, FIIa and FXa activity. The release of TFPI may well be responsible for the prolongation of aPTT, Heptest and PITT. IK-SSH may be further developed as an antithrombotic agent.

  12. Molecular chaperone properties of the high molecular weight aggregate from aged lens

    NASA Technical Reports Server (NTRS)

    Takemoto, L.; Boyle, D.; Spooner, B. S. (Principal Investigator)

    1994-01-01

    The high molecular weight aggregate (HMWA) fraction was isolated from the water soluble proteins of aged bovine lenses. Its composition and ability to inhibit heat-induced denaturation and aggregation were compared with the lower molecular weight, oligomeric fraction of alpha isolated from the same lens. Although the major components of both fractions were the alpha-A and alpha-B chains, the HMWA fraction possessed a decreased ability to protect other proteins against heat-induced denaturation and aggregation. Immunoelectron microscopy of both fractions demonstrated that alpha particles from the HMWA fraction contained increased amounts of beta and gamma crystallins, bound to a central region of the supramolecular complex. Together, these results demonstrate that alpha crystallins found in the HMWA fraction possess a decreased ability to protect against heat-induced denaturation and aggregation, and suggest that at least part of this decrease could be due to the increased presence of beta and gamma crystallins complexed to the putative chaperone receptor site of the alpha particles.

  13. Spectroscopic investigations, molecular interactions, and molecular docking studies on the potential inhibitor "thiophene-2-carboxylicacid"

    NASA Astrophysics Data System (ADS)

    Karthick, T.; Balachandran, V.; Perumal, S.

    2015-04-01

    Thiophene derivatives have been focused in the past decades due to their remarkable biological and pharmacological activities. In connection with that the conformational stability, spectroscopic characterization, molecular (inter- and intra-) interactions, and molecular docking studies on thiophene-2-carboxylicacid have been performed in this work by experimental FT-IR and theoretical quantum chemical computations. Experimentally recorded FT-IR spectrum in the region 4000-400 cm-1 has been compared with the scaled theoretical spectrum and the spectral peaks have been assigned on the basis of potential energy distribution results obtained from MOLVIB program package. The conformational stability of monomer and dimer conformers has been examined. The presence of inter- and intramolecular interactions in the monomer and dimer conformers have been explained by natural bond orbital analysis. The UV-Vis spectra of the sample in different solvents have been simulated and solvent effects were predicted by polarisable continuum model with TD-DFT/B3LYP/6-31+G(d,p) method. To test the biological activity of the sample, molecular docking (ligand-protein) simulations have been performed using SWISSDOCK web server. The full fitness (FF) score and binding affinity values revealed that thiophene-2-carboxylicacid can act as potential inhibitor against inflammation.

  14. Isolation of low-molecular-weight heparin/heparan sulfate from marine sources.

    PubMed

    Saravanan, Ramachandran

    2014-01-01

    The glycosaminoglycan (heparin and heparan sulfate) are polyanionic sulfated polysaccharides mostly recognized for its anticoagulant activity. In many countries, low-molecular-weight heparins have replaced the unfractionated heparin, owing to its high bioavailability, half-life, and less adverse effect. The low-molecular-weight heparins differ in mode of preparation (chemical or enzymatic synthesis and chromatography fractionations) and as a consequence in molecular weight distribution, chemical structure, and pharmacological activities. Bovine and porcine body parts are at present used for manufacturing of commercial heparins, and the appearance of mad cow disease and Creutzfeldt-Jakob disease in humans has limited the use of bovine heparin. Consequently, marine organisms come across the new resource for the production of low-molecular-weight heparin and heparan sulfate. The importance of this chapter suggests that the low-molecular-weight heparin and heparan sulfate from marine species could be alternative sources for commercial heparin.

  15. Arrangement of high molecular weight associated proteins on purified mammalian brain microtubules

    PubMed Central

    1977-01-01

    The arrangement of the high molecular weight proteins associated with the walls of reconstituted mammalian brain microtubules has been investigated by electron microscopy of negatively stained preparations. The images are found to be consistent with an arrangement whereby the high molecular weight molecules are spaced 12 tubulin dimers apart, i.e., 960 A, along each protofilament of the microtubule, in agreement with the relative stoichiometry of tubulin and high molecular weight protein. Molecules on neighbouring protofilaments seem to be staggered so that they give rise to a helical superlattice, which can be superimposed on the underlying tubulin lattice. In micrographs of disintegrating tubules there is some indication of lateral interactions between neighbouring high molecular weight molecules. When the microtubules are depolymerized into a mixture of short spirals and rings, the high molecular weight proteins appear to remain attached to their respective protofilaments. PMID:65355

  16. Discovery and optimization of triazine derivatives as ROCK1 inhibitors: molecular docking, molecular dynamics simulations and free energy calculations.

    PubMed

    Shen, Mingyun; Zhou, Shunye; Li, Youyong; Pan, Peichen; Zhang, Liling; Hou, Tingjun

    2013-03-01

    Rho-associated protein kinases (ROCK1 and ROCK2) are promising targets for a number of diseases, including cardiovascular disorders, nervous system diseases, cancers, etc. Recently, we have successfully identified a ROCK1 inhibitor (1) with the triazine core. In order to gain a deeper insight into the microscopic binding of this inhibitor with ROCK1 and design derivatives with improved potency, the interactions between ROCK1 and a series of triazine/pyrimidine-based inhibitors were studied by using an integrated computational protocol that combines molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and binding energy decomposition analysis. First, three docking protocols, rigid receptor docking, induced fit docking, QM-polarized ligand docking, were used to determine the binding modes of the studied inhibitors in the active site of ROCK1. The results illustrate that rigid receptor docking achieves the best performance to rank the binding affinities of the studied inhibitors. Then, based on the predicted structures from molecular docking, MD simulations and MM/GBSA free energy calculations were employed to determine the dynamic binding process and compare the binding modes of the inhibitors with different activities. The binding free energies predicted by MM/GBSA are in good agreement with the experimental bioactivities, and the analysis of the individual energy terms suggests that the van der Waals interaction is the major driving force for ligand binding. In addition, the residue-inhibitor interaction spectra were obtained by the MM/GBSA free energy decomposition analysis, and the important residues for achieving strong binding were highlighted, which affords important guidance for the rational design of novel ROCK inhibitors. Finally, a variety of derivatives of inhibitor 1 were designed and four of them showed promising potency according to the predictions. We expect that our study can provide significant insight into the

  17. Potent inhibitors of human organic anion transporters 1 and 3 from clinical drug libraries: discovery and molecular characterization.

    PubMed

    Duan, Peng; Li, Shanshan; Ai, Ni; Hu, Longqin; Welsh, William J; You, Guofeng

    2012-11-05

    Transporter-mediated drug-drug interactions in the kidney dramatically influence the pharmacokinetics and other clinical effects of drugs. Human organic anion transporters 1 (hOAT1) and 3 (hOAT3) are the major transporters in the basolateral membrane of kidney proximal tubules, mediating the rate-limiting step in the elimination of a broad spectrum of drugs. In the present study, we screened two clinical drug libraries against hOAT1 and hOAT3. Of the 727 compounds screened, 92 compounds inhibited hOAT1 and 262 compounds inhibited hOAT3. When prioritized based on the peak unbound plasma concentrations of these compounds, three inhibitors for hOAT1 and seven inhibitors for hOAT3 were subsequently identified with high inhibitory potency (>95%). Computational analyses revealed that inhibitors and noninhibitors can be differentiated from each other on the basis of several physicochemical features, including number of hydrogen-bond donors, number of rotatable bonds, and topological polar surface area (TPSA) for hOAT1; and molecular weight, number of hydrogen-bond donors and acceptors, TPSA, partition coefficient (log P(7.4)), and polarizability for hOAT3. Pharmacophore modeling identified two common structural features associated with inhibitors for hOAT1 and hOAT3, viz., an anionic hydrogen-bond acceptor atom, and an aromatic center separated by ∼5.7 Å. Such model provides mechanistic insights for predicting new OAT inhibitors.

  18. Endurance of high molecular weight carboxymethyl cellulose in corrosive environments

    NASA Astrophysics Data System (ADS)

    Murodov, M. M.; Rahmanberdiev, G. R.; Khalikov, M. M.; Egamberdiev, E. A.; Negmatova, K. C.; Saidov, M. M.; Mahmudova, N.

    2012-07-01

    Lignin obtained from the waste cooking liquor, formed after soda pulping process, is used as an inhibitor of NaCMC thermo oxidative degradation in presence of in extreme conditions during drilling oil wells. In this paper the schematic process of obtaining NaCMC by the principle of "monoapparat" on the basis of cellulose produced by non-wood cellulose materials is presented.

  19. Thermal and Mechanical Properties of Polyurethane-Diacetylene Segmented Copolymers. 1. Molecular Weight and Annealing Effects

    DTIC Science & Technology

    1989-05-31

    induced crystallization of the soft segments, the hard segment structure, weight fraction, and state of organization, the degree of phase separation...determined by the local environment of the chain. It is due to this dependence that polydiacetylene- based elastomers exhibit thermochromism and...Weight Determination. Molecular weights were determined on a Waters high pressure liquid chromatograph equipped with two Waters ultrastyragel columns

  20. Hyaluronan molecular weight is controlled by UDP-N-acetylglucosamine concentration in Streptococcus zooepidemicus.

    PubMed

    Chen, Wendy Yiting; Marcellin, Esteban; Hung, Jacky; Nielsen, Lars Keld

    2009-07-03

    The molecular weight of hyaluronan is important for its rheological and biological function. The molecular mechanisms underlying chain termination and hence molecular weight control remain poorly understood, not only for hyaluronan synthases but also for other beta-polysaccharide synthases, e.g. cellulose, chitin, and 1,3-betaglucan synthases. In this work, we manipulated metabolite concentrations in the hyaluronan pathway by overexpressing the five genes of the hyaluronan synthesis operon in Streptococcus equi subsp. zooepidemicus. Overexpression of genes involved in UDP-glucuronic acid biosynthesis decreased molecular weight, whereas overexpression of genes involved in UDP-N-acetylglucosamine biosynthesis increased molecular weight. The highest molecular mass observed was at 3.4 +/- 0.1 MDa twice that observed in the wild-type strain, 1.8 +/- 0.1 MDa. The data indicate that (a) high molecular weight is achieved when an appropriate balance of UDP-N-acetylglucosamine and UDP-glucuronic acid is achieved, (b) UDP-N-acetylglucosamine exerts the dominant effect on molecular weight, and (c) the wild-type strain has suboptimal levels of UDP-N-acetylglucosamine. Consistent herewith molecular weight correlated strongly (rho = 0.84, p = 3 x 10(-5)) with the concentration of UDP-N-acetylglucosamine. Data presented in this paper represent the first model for hyaluronan molecular weight control based on the concentration of activated sugar precursors. These results can be used to engineer strains producing high molecular weight hyaluronan and may provide insight into similar polymerization mechanisms in other polysaccharides.

  1. Immunochemical identity of the high and low molecular weight forms of Galapagos marine iguana hemoglobin.

    PubMed

    Higgins, P J

    1978-01-01

    1. Two forms of Galapagos marine iguana methemoglobin, with molecular weights of 140,000 and 70,000 daltons, were identified in iguana RBC lysates by Sephadex G-200 molecular sieve fractionation. 2. The 140,000 dalton ferric hemoglobin was isolated by DEAE-Sephadex A-50 ion-exchange chromatography and found to be pure by electrophoretic and immunological criteria. 3. Immunochemical analyses revealed the high and low molecular weight hemoglobins to be antigenically identical.

  2. Stopping cancer in its tracks: using small molecular inhibitors to target glioblastoma migrating cells.

    PubMed

    Mattox, Austin K; Li, Jing; Adamson, David C

    2012-12-01

    Glioblastoma multiforme (GBM) represents one of the most common aggressive types of primary brain tumors. Despite advances in surgical resection, novel neuroimaging procedures, and the most recent adjuvant radiotherapy and chemotherapy, the median survival after diagnosis is about 12-14 months. Targeting migrating GBM cells is a key research strategy in the fight against this devastating cancer. Though the vast majority of the primary tumor focus can be surgically resected, these migrating cells are responsible for its universal recurrence. Numerous strategies and technologies are being explored to target migrating glioma cells, with small molecular inhibitors as one of the most commonly studied. Small molecule inhibitors, such as protein kinase inhibitors, phosphorylation site inhibitors, protease inhibitors, and antisense oligonucleotides show promise in slowing the progression of this disease. A better understanding of these small molecule inhibitors and how they target various extra- and intracellular signaling pathways may eventually lead to a cure for GBM.

  3. Calculation of molecular weights of humic substances from colligative data: Application to aquatic humus and its molecular size fractions

    NASA Astrophysics Data System (ADS)

    Reuter, J. H.; Perdue, E. M.

    1981-11-01

    A rigorous mathematical expression for the dependence of colligative properties on acid dissociation of water soluble humic substances is presented. New data for number average molecular weights of a river derived humic material and its gel permeation Chromatographic fractions are compared with M¯n values obtained by a reevaluation of previously published experimental observations on soil and water fulvic acids. The results reveal a remarkable similarity of fulvic acids from widely different sources with respect to number-average molecular weight.

  4. Antioxidant activity of high molecular weight chitosan and N,O-quaternized chitosans.

    PubMed

    Wan, Ajun; Xu, Qing; Sun, Yan; Li, Huili

    2013-07-17

    The objective of this study was to evaluate the in vitro antioxidant activity of high molecular weight chitosan based films. Three kinds of water-soluble quaternized chitosans with high molecular weight, namely N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (400-HTCC and 1240-HTCC), N-(2-hydroxyl) propyl-3-triethyl ammonium chitosan chloride (400-HTEC and 1240-HTEC), and O-(2-hydroxyl) propyl-3- trimethyl ammonium chitosan chloride (400-O-HTCC) were prepared from high molecular weight chitosans (400 and 1240 kDa). The in vitro antioxidant activity of a high molecular weight chitosan (1240-CS) and five quaternized chitosans was evaluated and compared as radical scavengers against 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH•), hydroxyl radical (•OH), and superoxide radical (•O2(-)) using established methods, and the effect of the molecular weight, the concentration, the newly generated hydroxyl group, the extra introduced positive charge of quaternary ammonium salt group, etc., on the antioxidant activity of these high molecular weight chitosans is discussed. The data obtained in vitro models exhibited good antioxidant potency and suggested the possibility that high molecular weight chitosan based films could be effectively employed as natural antioxidant materials for application in the field of food and medicine.

  5. Immunostimulative Activity of Low Molecular Weight Chitosans in RAW264.7 Macrophages.

    PubMed

    Wu, Ning; Wen, Zheng-Shun; Xiang, Xing-Wei; Huang, Yan-Na; Gao, Yang; Qu, You-Le

    2015-09-30

    Chitosan and its derivatives such as low molecular weight chitosans (LMWCs) have been reported to exert many biological activities, such as antioxidant and antitumor effects. However, complex and molecular weight dependent effects of chitosan remain controversial and the mechanisms that mediate these complex effects are still poorly defined. This study was carried out to investigate the immunostimulative effect of different molecular weight chitosan in RAW264.7 macrophages. Our data suggested that two LMWCs (molecular weight of 3 kDa and 50 kDa) both possessed immunostimulative activity, which was dependent on dose and, at the higher doses, also on the molecular weight. LMWCs could significantly enhance the the pinocytic activity, and induce the production of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interferon-γ (IFN-γ), nitric oxide (NO) and inducible nitric oxide synthase (iNOS) in a molecular weight and concentration-dependent manner. LMWCs were further showed to promote the expression of the genes including iNOS, TNF-α. Taken together, our findings suggested that LMWCs elicited significantly immunomodulatory response through up-regulating mRNA expression of proinflammatory cytokines and activated RAW264.7 macrophage in a molecular weight- and concentration-dependent manner.

  6. Perchlorate-induced combustion of organic matter with variable molecular weights: Implications for Mars missions

    NASA Astrophysics Data System (ADS)

    Sephton, Mark A.; Lewis, James M. T.; Watson, Jonathan S.; Montgomery, Wren; Garnier, Carole

    2014-11-01

    Instruments on the Viking landers and Curiosity rover analyzed samples of Mars and detected carbon dioxide and organic compounds of uncertain origin. Mineral-assisted reactions are leading to uncertainty, particularly those involving perchlorate minerals which thermally decompose to produce chlorine and oxygen which can then react with organic matter to generate organochlorine compounds and carbon dioxide. Although generally considered a problem for interpretation, the release profiles of generated gases can indicate the type of organic matter present. We have performed a set of experiments with perchlorate and organic matter of variable molecular weights. Results indicate that organic susceptibility to thermal degradation and mineral-assisted reactions is related to molecular weight. Low molecular weight organic matter reacts at lower temperatures than its high molecular weight counterparts. The natural occurrence and association of organic matter with differing molecular weights helps to discriminate between contamination (usually low molecular weight organic matter only) and indigenous carbon (commonly low and high molecular weight organic matter together). Our results can be used to provide insights into data returning from Mars.

  7. Preparation of low molecular weight fucoidan by gamma-irradiation and its anticancer activity.

    PubMed

    Choi, Jong-il; Kim, Hyun-Joo

    2013-09-12

    Fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities. Recently, it has been reported that low molecular weight fucoidan has the enhanced antioxidant and anticoagulative activities. However, degradation techniques such as enzymolysis and acid hydrolysis for obtaining low molecular weight fucoidan, have the disadvantages such as narrow substrate specificity and unfavorable hydrolysis of side groups, respectively. In this study, low molecular weight fucoidan was prepared by gamma-irradiation. When fucoidan was gamma-irradiated, the molecular weight rapidly dropped to 38 kDa when the sample was irradiated at 10 kGy, then gradually dropped to 7 kDa without the significant elimination of the sulfate groups. Low molecular weight fucoidan had higher cytotoxicity than native fucoidan in cancer cells, such as AGS, MCF-7, and HepG-2. In addition, low molecular weight fucoidan showed higher inhibitory activity of cell transformation, which resulted in higher anticarcinogenicity. This result suggests that low molecular weight fucoidan with enhanced biological activities can be produced by a simple irradiation method without changing the functional groups.

  8. Time-dependent failure of amorphous poly-D,L-lactide: influence of molecular weight.

    PubMed

    Söntjens, Serge H M; Engels, Tom A P; Smit, Theo H; Govaert, Leon E

    2012-09-01

    The specific time-dependent deformation response of amorphous poly(lactic acid) (PLA) is known to lead to rapid failure of these materials in load-bearing situations. We have investigated this phenomenon in uniaxial compression on P(L)DLLA samples with various molecular weights. The experiments revealed a strong dependence of the yield stress on the applied strain rate. Lower molecular weights showed identical deformation kinetics as higher molecular weights, albeit at lower stress values. This dependence on molecular weight was incorporated into an Eyring-equation by introducing mobility through a virtual temperature that is shifted by the deviation of the T(g) from T(g,∞). Stress-dependent lifetime of polymer constructs was described by the use of this modified Eyring-equation, combined with a critical plastic strain. This model proves useful in predicting the molecular weight dependence of the time to failure, although it slightly overestimates life time at low stress levels for a material with very low molecular weight. The versatility of the model is demonstrated on e-beam sterilized PLDLLA, where the resulting reduction in molecular weight induces a substantial decrease in lifetime. A single T(g) measurement provides sufficient information to predict the decrease in lifetime.

  9. Assessing sedimentation equilibrium profiles in analytical ultracentrifugation experiments on macromolecules: from simple average molecular weight analysis to molecular weight distribution and interaction analysis.

    PubMed

    Harding, Stephen E; Gillis, Richard B; Adams, Gary G

    2016-01-01

    Molecular weights (molar masses), molecular weight distributions, dissociation constants and other interaction parameters are fundamental characteristics of proteins, nucleic acids, polysaccharides and glycoconjugates in solution. Sedimentation equilibrium analytical ultracentrifugation provides a powerful method with no supplementary immobilization, columns or membranes required. It is a particularly powerful tool when used in conjunction with its sister technique, namely sedimentation velocity. Here, we describe key approaches now available and their application to the characterization of antibodies, polysaccharides and glycoconjugates. We indicate how major complications, such as thermodynamic non-ideality, can now be routinely dealt with, thanks to a great extent to the extensive contribution of Professor Don Winzor over several decades of research.

  10. High molecular weight first generation PMR polyimides for 343 C applications

    NASA Technical Reports Server (NTRS)

    Malarik, D. C.; Vannucci, R. D.

    1992-01-01

    The effect of molecular weight on 343 C thermo-oxidative stability (TOS), mechanical properties, and processability, of the first generation PMR polyimides was studied. Graphite fiber reinforced PMR-15, PMR-30, PMR-50, and PMR-75 composites (corresponding to formulated molecular weights of 1500, 3000, 5000, and 7500, respectively) were fabricated using a simulated autoclave process. The data reveal that while alternate autoclave cure schedules are required for the high molecular weight resins, low void laminates can be fabricated which have significantly improved TDS over PMR-15, with only a small sacrifice in mechanical properties.

  11. Effect of sterilization irradiation on friction and wear of ultrahigh-molecular-weight polyethylene

    NASA Technical Reports Server (NTRS)

    Jones, W. R., Jr.; Hady, W. F.; Crugnola, A.

    1979-01-01

    The effect of sterilization gamma irradiation on the friction and wear properties of ultrahigh molecular weight polyethylene (UHMWPE) sliding against 316L stainless steel in dry air at 23 C was determined. A pin-on-disk apparatus was used. Experimental conditions included a 1-kilogram load, a 0.061- to 0.27-meter-per-second sliding velocity, and a 32000- to 578000-meter sliding distance. Although sterilization doses of 2.5 and 5.0 megarads greatly altered the average molecular weight and the molecular weight distribution, the friction and wear properties of the polymer were not significantly changed.

  12. High molecular weight first generation PMR polyimides for 343 C applications

    NASA Technical Reports Server (NTRS)

    Malarik, Diane C.; Vannucci, Raymond D.

    1991-01-01

    The effect of molecular weight on 343 C thermo-oxidative stability (TOS), mechanical properties, and processability, of the first generation PMR polyimides was studied. Graphite fiber reinforced PMR-15, PMR-30, PMR-50, and PMR-75 composites (corresponding to formulated molecular weights of 1500, 3000, 5000, and 7500, respectively) were fabricated using a simulated autoclave process. The data reveals that while alternate autoclave cure schedules are required for the high molecular weight resins, low void laminates can be fabricated which have significantly improved TOS over PMR-15, with only a small sacrifice in mechanical properties.

  13. Molecular dynamics simulations on the interactions of low molecular weight natural organic acids with C60.

    PubMed

    Sun, Qian; Xie, Hong-Bin; Chen, Jingwen; Li, Xuehua; Wang, Zhuang; Sheng, Lianxi

    2013-07-01

    As an important part of dissolved organic matter (DOM), low molecular weight organic acids (LOAs) may play a key role in the process for DOM stabilizing carbon nanomaterials (e.g. C60) suspensions in aquatic environment. In addition, both LOAs and C60 have been detected in the troposphere and therefore have a chance to interact with each other in the gaseous phase. However, the mechanism for LOAs-C60 interactions and their environmental implications need further investigations. In this study, molecular dynamics (MD) simulation was employed to investigate the interactions between both neutral and ionic LOAs with C60 in vacuum and water. The results showed that the adsorptions of all LOAs on C60 in energy are favorable, and the aromatic acids have stronger interactions with C60 than the aliphatic acids in vacuum and water. The interaction energies (Eint) of the LOA anions with C60 were weaker than those of their corresponding neutral LOA molecules. The models were also developed to predict and interpret Eint based on the results from MD simulations. Dispersion, induction and hydrophobic interactions were found to be the dominating factor in Eint. These findings indicate that cost-efficient MD simulation can be employed as an important tool to predict the adsorption behavior of LOAs on carbon nanomaterials.

  14. Progress of small molecular inhibitors in the development of anti-influenza virus agents

    PubMed Central

    Wu, Xiaoai; Wu, Xiuli; Sun, Qizheng; Zhang, Chunhui; Yang, Shengyong; Li, Lin; Jia, Zhiyun

    2017-01-01

    The influenza pandemic is a major threat to human health, and highly aggressive strains such as H1N1, H5N1 and H7N9 have emphasized the need for therapeutic strategies to combat these pathogens. Influenza anti-viral agents, especially active small molecular inhibitors play important roles in controlling pandemics while vaccines are developed. Currently, only a few drugs, which function as influenza neuraminidase (NA) inhibitors and M2 ion channel protein inhibitors, are approved in clinical. However, the acquired resistance against current anti-influenza drugs and the emerging mutations of influenza virus itself remain the major challenging unmet medical needs for influenza treatment. It is highly desirable to identify novel anti-influenza agents. This paper reviews the progress of small molecular inhibitors act as antiviral agents, which include hemagglutinin (HA) inhibitors, RNA-dependent RNA polymerase (RdRp) inhibitors, NA inhibitors and M2 ion channel protein inhibitors etc. Moreover, we also summarize new, recently reported potential targets and discuss strategies for the development of new anti-influenza virus drugs. PMID:28382157

  15. Purification of High Molecular Weight Kininogen and the Role of This Agent in Blood Coagulation

    PubMed Central

    Saito, Hidehiko

    1977-01-01

    Recent studies of individuals with high molecular weight (HMW) kininogen deficiency established the importance of this plasma protein for in vitro initiation of blood coagulation. In the present study, HMW-kininogen was highly purified from human plasma by monitoring its clot-promoting activity, using Fitzgerald trait plasma as a substrate. This preparation of HMW-kininogen revealed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (mol wt: 120,000) and released 1% of its weight as bradykinin upon incubation with plasma kallikrein. HMW-kininogen specifically repaired impaired surface-mediated plasma reactions of Fitzgerald trait plasma, but did not affect those of Hageman trait and Fletcher trait plasma. Kinin release from HMW-kininogen by trypsin, but not by plasma kallikrein, resulted in total loss of clot-promoting activity. No inhibitors of coagulation were found when all kinin activity was removed from HMW-kininogen by trypsin. The roles of HMW-kininogen, Hageman factor (HF, Factor XII), plasma prekallikrein (Fletcher factor), and plasma thromboplastin antecedent (PTA, Factor XI) in blood coagulation were studied in a purified system. HMW-kininogen was absolutely required for activation of PTA by HF and ellagic acid. The yield of activated PTA was proportional to the amount of HF, HMW-kininogen, and PTA in the mixtures, suggesting that, to activate PTA, these three proteins might form a complex in the presence of ellagic acid. No fragmentation of HF was found under these conditions. In contrast to HF, HF-fragments (mol wt: 30,000) activated PTA in the absence of HMW-kininogen and ellagic acid. Thus, it appears that in the present study PTA was activated in two distinct ways. Which pathway is the major one in whole plasma remains to be determined. Images PMID:893664

  16. Evaluation of diclofenac sodium sustained release matrix pellets: impact of polyethylene glycols molecular weight.

    PubMed

    Ibrahim, A; Shazly, A

    2014-01-01

    Sustained release matrix pellets loaded with 5% w/w diclofenac sodium (DS) were prepared using extrusion/spheronization technique. Different polyethylene glycols (PEGs) of different molecular weight, namely PEG 2000, PEG 4000 and PEG 6000, were mixed with avicel PH 101 in different weight ratios to manufacture the pellet formulations and water was used as a binder. Mix torque rheometer was used to characterize the pellets' wet mass. Also, the prepared pellets were characterized for their particle sizes, DS content, shape and morphology as well as the in vitro drug release. The results showed increasing PEG weight ratio resulted in a reduction of wet mass torque as well as binder ratio, especially at PEG high weight ratios (30% and 50%) and the extent of lowering wet mass peak torque was inversely proportional to PEG molecular weight. The manufactured pellets exhibited size range of 993 μm to 1085 μm with small span values. The drug release from pellets was governed by the molecular weight of PEG used, since increasing PEG molecular weight resulted in slowing the drug release rate from pellets, but increasing its level resulted in enhancing release rate. This was attributed to increasing pellet wet mass peak torque by increasing PEG molecular weight and lowering it by increasing PEG level. The prepared pellets showed non-Fickian or anomalous drug release or the coupled diffusion/polymer relaxation.

  17. EVALUATION OF DICLOFENAC SODIUM SUSTAINED RELEASE MATRIX PELLETS: IMPACT OF POLYETHYLENE GLYCOLS MOLECULAR WEIGHT.

    PubMed

    Ibrahim, Mohamed A; Shazly, Gamal A

    2015-01-01

    Sustained release matrix pellets loaded with 5% w/w diclofenac sodium (DS) were prepared using extrusion/spheronization technique. Different polyethylene glycols (PEGs) of different molecular weight, namely PEG 2000, PEG 4000 and PEG 6000 were mixed with avicel PH 101® in different weight ratios to manufacture the pellet formulations and water was used as a binder. Mix torque rheomter was used to characterize the pellets' wet mass. Also, the prepared pellets were characterized for their particle sizes, DS content, shape and morphology as well as the in vitro drug release. The results showed that increasing PEG weight ratio resulted in a reduction of wet mass torque as well as binder ratio, especially at PEG high weight ratios (30% and 50%) and the extent of lowering wet mass peak torque was inversely proportional to PEG molecular weight. The manufactured pellets exhibited size range of 993 to 1085 µm with small span values. The drug release from pellets was governed by the molecular weight of PEG used, since increasing PEG molecular weight resulted in slowing the drug release rate from pellets, but increasing its level resulted in enhancing release rate. This was attributed to increasing pellet wet mass peak torque by increasing PEG molecular weight and lowering it by increasing PEG level. The prepared pellets showed non-Fickian or anomalous drug release or the coupled diffusion/polymer relaxation.

  18. Intrapleural low-molecular-weight urokinase or tissue plasminogen activator versus single-chain urokinase in tetracycline-induced pleural loculation in rabbits.

    PubMed

    Idell, Steven; Azghani, Ali; Chen, Shande; Koenig, Kathy; Mazar, Andrew; Kodandapani, Lalitha; Bdeir, Khalil; Cines, Douglas; Kulikovskaya, Irina; Allen, Timothy

    2007-01-01

    The authors compared the ability of a single dose of the proenzyme single-chain urokinase (scuPA), low-molecular-weight urokinase, tissue plasminogen activator (tPA), or a mutant site-inactive scuPA to resolve intrapleural loculations at 72 to 96 hours after tetracycline-induced pleural injury in rabbits. Both scuPA and tPA reversed loculations at 96 hours after injury P < or = .001, whereas low-molecular-weight urokinase and the scuPA mutant were ineffective. scuPA and tPA generated inhibitor complexes, induced fibrinolytic activity, and quenched plasminogen activator-1 activity in pleural fluids. The authors conclude that scuPA reverses loculations as effectively as tPA at clinically applied intrapleural doses, whereas low-molecular-weight urokinase was ineffective.

  19. Discovery of Potential Inhibitors of Aldosterone Synthase from Chinese Herbs Using Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation Studies

    PubMed Central

    Lu, Fang; Qiao, Liansheng; Chen, Xi; Li, Gongyu

    2016-01-01

    Aldosterone synthase (CYP11B2) is a key enzyme for the biosynthesis of aldosterone, which plays a significant role for the regulation of blood pressure. Excess aldosterone can cause the dysregulation of the renin-angiotensin-aldosterone system (RAAS) and lead to hypertension. Therefore, research and development of CYP11B2 inhibitor are regarded as a novel approach for the treatment of hypertension. In this study, the pharmacophore models of CYP11B2 inhibitors were generated and the optimal model was used to identify potential CYP11B2 inhibitors from the Traditional Chinese Medicine Database (TCMD, Version 2009). The hits were further refined by molecular docking and the interactions between compounds and CYP11B2 were analyzed. Compounds with high Fitvalue, high docking score, and expected interactions with key residues were selected as potential CYP11B2 inhibitors. Two most promising compounds, ethyl caffeate and labiatenic acid, with high Fitvalue and docking score were reserved for molecular dynamics (MD) study. All of them have stability of ligand binding which suggested that they might perform the inhibitory effect on CYP11B2. This study provided candidates for novel drug-like CYP11B2 inhibitors by molecular simulation methods for the hypertension treatment. PMID:27781210

  20. Antioxidant activity of low molecular weight alginate produced by thermal treatment.

    PubMed

    Kelishomi, Zahra Habibi; Goliaei, Bahram; Mahdavi, Hossein; Nikoofar, Alireza; Rahimi, Mahmood; Moosavi-Movahedi, Ali Akbar; Mamashli, Fatemeh; Bigdeli, Bahareh

    2016-04-01

    By definition, antioxidants are molecules that inhibit the oxidation of other molecules. Therefore, such compounds have very important clinical roles. In this study alginate polymer was depolymerized by heat treatment. The resulting low molecular weight alginates were investigated by UV-visible spectroscopy, Viscometry, Dynamic light scattering and FT-IR spectroscopy techniques. Antioxidant properties of these heat products were studied by ABTS and superoxide radical scavenging assays. Results showed that heating caused breaks in the polymer chain and so generation of low molecular weight alginates. Antioxidant measurements confirmed antioxidant activity of alginate increased upon a decrease in molecular weight. Therefore, low molecular weight alginate produced by heating could be considered as a stronger antioxidant than alginate polymer. These products could be useful for industrial and biomedical applications.

  1. Bacillus subtilis 168 levansucrase (SacB) activity affects average levan molecular weight.

    PubMed

    Porras-Domínguez, Jaime R; Ávila-Fernández, Ángela; Miranda-Molina, Afonso; Rodríguez-Alegría, María Elena; Munguía, Agustín López

    2015-11-05

    Levan is a fructan polymer that offers a variety of applications in the chemical, health, cosmetic and food industries. Most of the levan applications depend on levan molecular weight, which in turn depends on the source of the synthesizing enzyme and/or on reaction conditions. Here we demonstrate that in the particular case of levansucrase from Bacillus subtilis 168, enzyme concentration is also a factor defining the molecular weight levan distribution. While a bimodal distribution has been reported at the usual enzyme concentrations (1 U/ml equivalent to 0.1 μM levansucrase) we found that a low molecular weight normal distribution is solely obtained al high enzyme concentrations (>5 U/ml equivalent to 0.5 μM levansucrase) while a high normal molecular weight distribution is synthesized at low enzyme doses (0.1 U/ml equivalent to 0.01 μM of levansucrase).

  2. Simple nanoparticle-based luminometric method for molecular weight determination of polymeric compounds.

    PubMed

    Pihlasalo, Sari; Virtamo, Maria; Legrand, Nicolas; Hänninen, Pekka; Härmä, Harri

    2014-01-21

    A nanoparticle-based method utilizing time-resolved luminescence resonance energy transfer (TR-LRET) was developed for molecular weight determination. This mix-and-measure nanoparticle method is based on the competitive adsorption between the analyte and the acceptor-labeled protein to donor Eu(III) nanoparticles. The size-dependent adsorption of molecules enables the molecular weight determination of differently sized polymeric compounds down to a concentration level of micrograms per liter. The molecular weight determination from 1 to 10 kDa for polyamino acids and from 0.3 to 70 kDa for polyethylene imines is demonstrated. The simple and cost-effective nanoparticle method as microtiter plate assay format shows great potential for the detection of the changes in molecular weight or for quantification of differently sized molecules in biochemical laboratories and in industrial polymeric processes.

  3. Ultra-low-molecular-weight heparins: precise structural features impacting specific anticoagulant activities.

    PubMed

    Lima, Marcelo A; Viskov, Christian; Herman, Frederic; Gray, Angel L; de Farias, Eduardo H C; Cavalheiro, Renan P; Sassaki, Guilherme L; Hoppensteadt, Debra; Fareed, Jawed; Nader, Helena B

    2013-03-01

    Ultra-low-molecular-weight heparins (ULMWHs) with better efficacy and safety ratios are under development; however, there are few structural data available. The main structural features and molecular weight of ULMWHs were studied and compared to enoxaparin. Their monosaccharide composition and average molecular weights were determined and preparations studied by nuclear magnetic resonance spectroscopy, scanning ultraviolet spectroscopy, circular dichroism and gel permeation chromatography. In general, ULMWHs presented higher 3-O-sulphated glucosamine and unsaturated uronic acid residues, the latter being comparable with their higher degree of depolymerisation. The analysis showed that ULMWHs are structurally related to LMWHs; however, their monosaccharide/oligosaccharide compositions and average molecular weights differed considerably explaining their different anticoagulant activities. The results relate structural features to activity, assisting the development of new and improved therapeutic agents, based on depolymerised heparin, for the prophylaxis and treatment of thrombotic disorders.

  4. Effect of protein molecular weight on the mass transfer in protein mixing

    NASA Astrophysics Data System (ADS)

    Asad, Ahmed; Chai, Chuan; Wu, JiangTao

    2012-03-01

    The mixing of protein solutions with that of precipitating agents is very important in protein crystallization experiments. In this work, the interferometry images were recorded during the mixing of two proteins with different molecular weights: lysozyme of ˜14.6 kDa, trypsin of ˜23.3 kDa and pepsin of ˜34.8 kDa were placed in a Mach-Zehnder interferometer. The protein molecular weight dependence on the competition of the transport process and kinetics at the interface was studied. The concentration profiles of protein solutions were calculated to analyze the mass transfer during the mixing process. It was observed that the mass transfer process is more efficient during the mixing of proteins with higher molecular weights. In addition, the more rapid concentration changes above the interface suggest that convection may dominate the diffusion. The phenomenon of convection is higher in the protein solutions with higher molecular weight.

  5. The chemical functionalized platinum nanodendrites: The effect of chemical molecular weight on electrocatalytic property

    NASA Astrophysics Data System (ADS)

    Xu, Guang-Rui; Han, Shu-He; Liu, Zong-Huai; Chen, Yu

    2016-02-01

    The surface chemical functionalization of noble metal nanocrystals is a promising strategy for improving the catalytic/electrocatalytic activity and selectivity of noble metal nanocrystals. In this work, we successfully synthesize the polyallylamine (PAA) with different molecular weight functionalized Pt nanodendrites (Pt-NDs) using a facile hydrothermal reduction method. The morphology and surface composition are investigated by transmission electron microscopy, element map, and thermogravimetric analysis. Furthermore, we detailedly investigate the effect of the molecular weight of PAA on the electrochemical property of the functionalized Pt-NDs. Electrochemical measurements show only low molecular weight PAA functionalized Pt-NDs allow electrolytes to access freely the Pt sites. Meanwhile, the low molecular weight PAA functionalized Pt-NDs show the excellent selectivity and activity for the oxygen reduction reaction in the presence of methanol.

  6. Molecular mechanism of viral resistance to a potent non-nucleoside inhibitor unveiled by molecular simulations.

    PubMed

    Asthana, Shailendra; Shukla, Saumya; Ruggerone, Paolo; Vargiu, Attilio V

    2014-11-11

    Recently, we reported on a potent benzimidazole derivative (227G) that inhibits the growth of the bovine viral diarrhea virus (BVDV) in cell-based and enzyme assays at nanomolar concentrations. The target of 227G is the viral RNA-dependent RNA polymerase (RdRp), and the I261M mutation located in motif I of the RdRp finger domain was found to induce drug resistance. Here we propose a molecular mechanism for the retained functionality of the enzyme in the presence of the inhibitor, on the basis of a thorough computational study of the apo and holo forms of the BVDV RdRp either in the wild type (wt) or in the form carrying the I261M mutation. Our study shows that although the mutation affects to some extent the structure of the apoenzyme, the functional dynamics of the protein appear to be largely maintained, which is consistent with the retained functionality of this natural mutant. Despite the binding site of 227G not collapsing or undergoing drastic structural changes upon introduction of the I261M substitution, these alterations reflect crucially on the binding mode of 227G, which is significantly different from that found in wt RdRp. In particular, while in the wt system the four loops lining the template entrance site embrace 227G and close the template passageway, in the I261M variant the template entrance is only marginally occluded, allowing in principle the translocation of the template to the interior of the enzyme. In addition, the mutated enzyme in the presence of 227G retains several characteristics of the wt apoprotein. Our work provides an original molecular picture of a resistance mechanism that is consistent with published experimental data.

  7. High and low molecular weight hyaluronic acid differentially influence macrophage activation.

    PubMed

    Rayahin, Jamie E; Buhrman, Jason S; Zhang, Yu; Koh, Timothy J; Gemeinhart, Richard A

    2015-07-13

    Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs.

  8. High and low molecular weight hyaluronic acid differentially influence macrophage activation

    PubMed Central

    Rayahin, Jamie E.; Buhrman, Jason S.; Zhang, Yu; Koh, Timothy J.; Gemeinhart, Richard A.

    2015-01-01

    Macrophages exhibit phenotypic diversity permitting wide-ranging roles in maintaining physiologic homeostasis. Hyaluronic acid, a major glycosaminoglycan of the extracellular matrix, has been shown to have differential signaling based on its molecular weight. With this in mind, the main objective of this study was to elucidate the role of hyaluronic acid molecular weight on macrophage activation and reprogramming. Changes in macrophage activation were assessed by activation state selective marker measurement, specifically quantitative real time polymerase chain reaction, and cytokine enzyme-linked immunoassays, after macrophage treatment with differing molecular weights of hyaluronic acid under four conditions: the resting state, concurrent with classical activation, and following inflammation involving either classically or alternatively activated macrophages. Regardless of initial polarization state, low molecular weight hyaluronic acid induced a classically activated-like state, confirmed by up-regulation of pro-inflammatory genes, including nos2, tnf, il12b, and cd80, and enhanced secretion of nitric oxide and TNF-α. High molecular weight hyaluronic acid promoted an alternatively activated-like state, confirmed by up regulation of pro-resolving gene transcription, including arg1, il10, and mrc1, and enhanced arginase activity. Overall, our observations suggest that macrophages undergo phenotypic changes dependent on molecular weight of hyaluronan that correspond to either (1) pro-inflammatory response for low molecular weight HA or (2) pro-resolving response for high molecular weight HA. These observations bring significant further understanding of the influence of extracellular matrix polymers, hyaluronic acid in particular, on regulating the inflammatory response of macrophages. This knowledge can be used to guide the design of HA-containing biomaterials to better utilize the natural response to HAs. PMID:26280020

  9. Corner rounding in EUV photoresist: tuning through molecular weight, PAG size, and development time

    SciTech Connect

    Anderson, Christopher; Daggett, Joe; Naulleau, Patrick

    2009-12-31

    In this paper, the corner rounding bias of a commercially available extreme ultraviolet photoresist is monitored as molecular weight, photoacid generator (PAG) size, and development time are varied. These experiments show that PAG size influences corner biasing while molecular weight and development time do not. Large PAGs are shown to exhibit less corner biasing, and in some cases, lower corner rounding, than small PAGs. In addition, heavier resist polymers are shown to exhibit less corner rounding than lighter ones.

  10. Production of nabumetone nanoparticles: Effect of molecular weight, concentration and nature of cellulose ether stabiliser.

    PubMed

    Goodwin, D J; Martini, L G; Lawrence, M J

    2016-12-05

    The ability of a range of hydrophilic nonionic cellulose ethers (CEs) (namely methylhydroxethylcellulose, hydroxypropylmethylcellulose, ethylhydroxyethylcellulose, hydroxyethylcellulose and hydroxypropylcellulose) to prepare stable nabumetone nanoparticles (<1000nm, as measured by laser diffraction) using wet-bead milling has been investigated. Due to the limited range of CE molecular weights commercially available, the CEs were degraded using ultrasonication for varying lengths of time to yield CEs of lower molecular weight. Of the CEs tested, only hydroxyethylcellulose was found not to stabilise the production of nabumetone nanoparticles at any of the molecular weights tested, namely viscosity average molecular weights (Mv) in the range of 236-33kg/mol. All other CEs successfully stabilised nabumetone nanoparticles, with the lower molecular weight/viscosity polymers within a series being more likely to result in nanoparticle production than their higher molecular weight counterparts. Unfortunately due to the nature of the ultrasonication process, it was not possible to compare the size of nabumetone particles produced using polymers of identical Mv. There was, however, enough similarity in the Mv of the various polymers to draw the general conclusion that there was no strong correlation between the Mv of the various polymers and their ability to produce nanoparticles. For example hydroxypropylcellulose of 112.2kg/mol or less successfully produced nanoparticles while only ethylhydroxyethylcellulose and hydroxypropylmethyl polymers of 52 and 38.8kg/mol or less produced nanoparticles. These results suggest that polymer molecular weight is not the only determinant of nanoparticle production and that structure of the polymer is at least as important as its molecular weight. In particular the hydrophobic nature of the CE was thought to be an important factor in the production of nabumetone nanoparticles: the more hydrophobic the polymer, the stronger its interaction

  11. Control of molecular weight of polystyrene using the reverse iodine transfer polymerization (RITP)-emulsion technique.

    PubMed

    Oh, Hyeong Geun; Shin, Hongcheol; Jung, Hyejun; Lee, Byung Hyung; Choe, Soonja

    2011-01-15

    The RITP-emulsion polymerization of styrene in the presence of molecular iodine has been successfully performed using potassium persulfate (KPS) as an initiator and 1-hexadecanesulfonate as an emulsifier under argon atmosphere at 80°C for 7 hrs in the absence of light. The effects of the iodine concentration, molar ratio between KPS and iodine, and solid contents on the molecular weight of polystyrene (PS) were studied. As the iodine concentration increased from 0.05 to 0.504 mmol under the fixed [KPS]/[I(2)] ratio at 4.5, the weight-average molecular weight of PS substantially decreased from 126,120 to 35,690 g/mol, the conversion increased from 85.0% to 95.2%, and the weight-average particle diameter decreased from 159 to 103 nm. In addition, as the ratio of [KPS]/[I(2)] increased from 0.5 to 6.0 at the fixed [I(2)] of 0.504 mmol, the weight-average molecular weight of PS decreased from 72,170 to 30,640 g/mol with high conversion between 81.7% and 96.5%. Moreover, when the styrene solid content increased from 10 to 40 wt.% at the fixed [KPS]/[I(2)] ratio of 4.5, the weight-average molecular weight of PS varied between 33,500 and 37,200 g/mol, the conversion varied between 94.9% and 89.7% and the weight-average diameter varied from 122 to 205 nm. Thus, the control of molecular weight of PS less than 100,000g/mol with high conversion (95%) and particle stability of up to 40 wt.% solid content were easily achieved through the usage of iodine with suitable ratio of [KPS]/[I(2)] in the RITP-emulsion polymerization technique, which is of great industrial importance.

  12. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors.

    PubMed

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-11-16

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors.

  13. An Investigation of Molecular Docking and Molecular Dynamic Simulation on Imidazopyridines as B-Raf Kinase Inhibitors

    PubMed Central

    Xie, Huiding; Li, Yupeng; Yu, Fang; Xie, Xiaoguang; Qiu, Kaixiong; Fu, Jijun

    2015-01-01

    In the recent cancer treatment, B-Raf kinase is one of key targets. Nowadays, a group of imidazopyridines as B-Raf kinase inhibitors have been reported. In order to investigate the interaction between this group of inhibitors and B-Raf kinase, molecular docking, molecular dynamic (MD) simulation and binding free energy (ΔGbind) calculation were performed in this work. Molecular docking was carried out to identify the key residues in the binding site, and MD simulations were performed to determine the detail binding mode. The results obtained from MD simulation reveal that the binding site is stable during the MD simulations, and some hydrogen bonds (H-bonds) in MD simulations are different from H-bonds in the docking mode. Based on the obtained MD trajectories, ΔGbind was computed by using Molecular Mechanics Generalized Born Surface Area (MM-GBSA), and the obtained energies are consistent with the activities. An energetic analysis reveals that both electrostatic and van der Waals contributions are important to ΔGbind, and the unfavorable polar solvation contribution results in the instability of the inhibitor with the lowest activity. These results are expected to understand the binding between B-Raf and imidazopyridines and provide some useful information to design potential B-Raf inhibitors. PMID:26580609

  14. Protein-binding affinity of leucaena condensed tannins of differing molecular weights.

    PubMed

    Huang, Xiao Dan; Liang, Juan Boo; Tan, Hui Yin; Yahya, Rosiyah; Long, Ruijun; Ho, Yin Wan

    2011-10-12

    Depending on their source, concentration, chemical structure, and molecular weight, condensed tannins (CTs) form insoluble complexes with protein, which could lead to ruminal bypass protein, benefiting animal production. In this study, CTs from Leuceana leucocephala hybrid were fractionated into five fractions by a size exclusion chromatography procedure. The molecular weights of the CT fractions were determined using Q-TOF LC-MS, and the protein-binding affinities of the respective CT fractions were determined using a protein precipitation assay with bovine serum albumin (BSA) as the standard protein. The calculated number-average molecular weights (M(n)) were 1348.6, 857.1, 730.1, 726.0, and 497.1, and b values (the b value represents the CT quantity that is needed to bind half of the maximum precipitable BSA) of the different molecular weight fractions were 0.381, 0.510, 0.580, 0.636, and 0.780 for fractions 1, 2, 3, 4, and 5, respectively. The results indicated that, in general, CTs of higher molecular weight fractions have stronger protein-binding affinity than those of lower molecular weights. However, the number of hydroxyl units within the structure of CT polymers also affects the protein-binding affinity.

  15. Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films.

    PubMed

    Andersson, Helene; Hjärtstam, Johan; Stading, Mats; von Corswant, Christian; Larsson, Anette

    2013-01-23

    Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the films after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.

  16. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate).

    PubMed

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati; Water, Jorrit J; Baldursdottír, Stefania; Almdal, Kristoffer; Beck-Broichsitter, Moritz

    2017-02-23

    Poly(ethylene carbonate) (PEC) is an unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196 kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, eroding-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives correlated well with the observed in vitro half-times of drug delivery (R(2)=0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro incubations with cholesterol esterase. Interestingly, SEM analysis indicated a distinct surface erosion process for enzyme-, macrophage- and in vivo-treated polymer films in a molecular weight-dependent manner. Overall, the molecular weight of surface-eroding PEC was identified as an essential parameter to control the spatial and temporal on-demand degradation and drug release from the employed delivery system.

  17. Western blotting of high and low molecular weight proteins using heat.

    PubMed

    Kurien, Biji T; Scofield, R Hal

    2015-01-01

    A method for the electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate (SDS) polyacrylamide gel is described here. The transfer was performed with heated (70-75 °C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight antigens (molecular weight protein standards, a purified protein, and proteins from a human tissue extract) could be carried out in 10 min for a 7 % (0.75 mm) SDS polyacrylamide gel. For 10 and 12.5 % gels (0.75 mm) the corresponding time was 15 min. A complete transfer could be carried out in 20 min for 7, 10, and 12.5 % gels (1.5 mm gels). The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. The heat mediated transfer method was compared with a conventional transfer protocol, under similar conditions. The conventional method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is particularly useful for the transfer of high molecular weight proteins, very rapid, and avoids the use of methanol.

  18. Ultrarapid electrophoretic transfer of high and low molecular weight proteins using heat.

    PubMed

    Kurien, Biji T; Scofield, R Hal

    2009-01-01

    An ultrarapid method for the electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate (SDS) polyacrylamide gel is described here. The transfer was performed with heated (70-75 degrees C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight antigens (molecular weight protein standards, a purified protein, and proteins from a human tissue extract) could be carried out in 10 min for a 7% (0.75 mm) SDS polyacrylamide gel. For 10 and 12.5% gels (0.75 mm) the corresponding time was 15 min. A complete transfer could be carried out in 20 min for 7, 10, and 12.5% gels (1.5 mm gels). The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. The heat mediated transfer method was compared with a conventional transfer protocol, under similar conditions. The conventional method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is particularly useful for the transfer of high molecular weight proteins, very rapid, and avoids the use of methanol.

  19. Occurrence of a multimeric high-molecular-weight glyceraldehyde-3-phosphate dehydrogenase in human serum.

    PubMed

    Kunjithapatham, Rani; Geschwind, Jean-Francois; Devine, Lauren; Boronina, Tatiana N; O'Meally, Robert N; Cole, Robert N; Torbenson, Michael S; Ganapathy-Kanniappan, Shanmugasundaram

    2015-04-03

    Cellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a phylogenetically conserved, ubiquitous enzyme that plays an indispensable role in energy metabolism. Although a wealth of information is available on cellular GAPDH, there is a clear paucity of data on its extracellular counterpart (i.e., the secreted or extracellular GAPDH). Here, we show that the extracellular GAPDH in human serum is a multimeric, high-molecular-weight, yet glycolytically active enzyme. The high-molecular-weight multimers of serum GAPDH were identified by immunodetection on one- and two-dimensional gel electrophoresis using multiple antibodies specific for various epitopes of GAPDH. Partial purification of serum GAPDH by DEAE Affigel affinity/ion exchange chromatography further established the multimeric composition of serum GAPDH. In vitro data demonstrated that human cell lines secrete a multimeric, high-molecular-weight enzyme similar to that of serum GAPDH. Furthermore, LC-MS/MS analysis of extracellular GAPDH from human cell lines confirmed the presence of unique peptides of GAPDH in the high-molecular-weight subunits. Furthermore, data from pulse-chase experiments established the presence of high-molecular-weight subunits in the secreted, extracellular GAPDH. Taken together, our findings demonstrate the presence of a high-molecular-weight, enzymatically active secretory GAPDH in human serum that may have a hitherto unknown function in humans.

  20. Molecular characterization of macbecin as an Hsp90 inhibitor.

    PubMed

    Martin, Christine J; Gaisser, Sabine; Challis, Iain R; Carletti, Isabelle; Wilkinson, Barrie; Gregory, Matthew; Prodromou, Chrisostomos; Roe, S Mark; Pearl, Laurence H; Boyd, Susan M; Zhang, Ming-Qiang

    2008-05-08

    Macbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC50 = 2 microM) and binding with higher affinity (Kd = 0.24 microM). Structural studies reveal significant differences in their Hsp90 binding characteristics, and macbecin-induced tumor cell growth inhibition is accompanied by characteristic degradation of Hsp90 client proteins. Macbecin significantly reduced tumor growth rates (minimum T/C: 32%) in a DU145 murine xenograft. Macbecin thus represents an attractive lead for further optimization.

  1. 21 CFR 177.1440 - 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... minimum molecular weight 10,000. 177.1440 Section 177.1440 Food and Drugs FOOD AND DRUG ADMINISTRATION... § 177.1440 4,4′-Isopropylidenediphenol-epichlorohydrin resins minimum molecular weight 10,000. 4,4′-Isopropylidenediphenol-epichlo-rohydrin resins having a minimum molecular weight of 10,000 may be safely used as...

  2. Molecular dynamics of protein kinase-inhibitor complexes: a valid structural information.

    PubMed

    Caballero, Julio; Alzate-Morales, Jans H

    2012-01-01

    Protein kinases (PKs) are key components of protein phosphorylation based signaling networks in eukaryotic cells. They have been identified as being implicated in many diseases. High-resolution X-ray crystallographic data exist for many PKs and, in many cases, these structures are co-complexed with inhibitors. Although this valuable information confirms the precise structure of PKs and their complexes, it ignores the dynamic movements of the structures which are relevant to explain the affinities and selectivity of the ligands, to characterize the thermodynamics of the solvated complexes, and to derive predictive models. Atomistic molecular dynamics (MD) simulations present a convenient way to study PK-inhibitor complexes and have been increasingly used in recent years in structure-based drug design. MD is a very useful computational method and a great counterpart for experimentalists, which helps them to derive important additional molecular information. That enables them to follow and understand structure and dynamics of protein-ligand systems with extreme molecular detail on scales where motion of individual atoms can be tracked. MD can be used to sample dynamic molecular processes, and can be complemented with more advanced computational methods (e.g., free energy calculations, structure-activity relationship analysis). This review focuses on the most commonly applications to study PK-inhibitor complexes using MD simulations. Our aim is that researchers working in the design of PK inhibitors be aware of the benefits of this powerful tool in the design of potent and selective PK inhibitors.

  3. A nanostructural investigation of glassy gelatin oligomers: molecular organization and interactions with low molecular weight diluents

    NASA Astrophysics Data System (ADS)

    Roussenova, M.; Enrione, J.; Diaz-Calderon, P.; Taylor, A. J.; Ubbink, J.; Alam, M. A.

    2012-03-01

    The effects of low molecular weight diluents (namely water and glycerol) on the nanostructure and thermodynamic state of low water content gelatin matrices are explored systematically by combining positron annihilation lifetime spectroscopy (PALS) with calorimetric measurements. Bovine gelatin matrices with a variation in the glycerol content (0-10 wt.%) are equilibrated in a range of water activities (aw = 0.11-0.68, T = 298 K). Both water and glycerol reduce the glass transition temperature, Tg, and the temperature of dissociation of the ordered triple helical segments, Tm, while having no significant effect on the level of re-naturation of the gelatin matrices. Our PALS measurements show that over the concentration range studied, glycerol acts as a packing enhancer and in the glassy state it causes a nonlinear decrease in the average hole size, vh, of the gelatin matrices. Finally, we report complex changes in vh for the gelatin matrices as a function of the increasing level of hydration. At low water contents (Qw ˜ 0.01-0.10), water acts as a plasticizer, causing a systematic increase in vh. Conversely, for water contents higher than Qw ˜ 0.10, vh is found to decrease, as small clusters of water begin to form between the polypeptide chains.

  4. Molecular modeling of various peptide sequences of gliadins and low-molecular-weight glutenin subunits.

    PubMed

    Yaşar, Fatih; Celik, Süeda; Köksel, Hamit

    2003-08-01

    The contribution of the three-dimensional structures of one heptapeptide (PQPQPFP) sequence and one pentapeptide (PQQPY) repeat sequence of alpha/beta-gliadins, one heptapeptide (PQQPFPQ) repeat sequence of gamma-gliadins, two heptapeptide (PQQPPFS and QQQQPVL) repeat motifs of low-molecular-weight (LMW) subunits and a tetrapeptide sequence in polyQ region of S-rich prolamins to their conformations are investigated by using the recently developed multicanonical simulation procedure. Ramachandran plots were prepared and analysed to predict the relative occurrence probabilities of gamma-tutn, gamma-turn, and helical structures. The probability of inverse 7-turn was generally higher than that of beta-turns in all sequences investigated. Occurrence probability of helical structure in the repetitive domain of gliadins was low. Structural predictions of QQQQPVL sequence of LMW-glutenin subunits and QQQQ sequence in the polyQ region of S-rich prolamins indicate the presence of helical structures with the probability of >20%. The probability of helical structure significantly decreased around 100 degrees C.

  5. Use of Kinematic Viscosity Data for the Evaluation of the Molecular Weight of Petroleum Oils

    ERIC Educational Resources Information Center

    Maroto, J. A.; Quesada-Perez, M.; Ortiz-Hernandez, A. J.

    2010-01-01

    A new laboratory procedure for the evaluation of the mean molecular weight (mean relative molecular mass) of petroleum oils with high accuracy is described. The density and dynamic viscosity of three commercial petroleum oils are measured at different temperatures. These experimental data are used to calculate the kinematic viscosity as a function…

  6. Interaction Analysis of T7 RNA Polymerase with Heparin and Its Low Molecular Weight Derivatives – An In Silico Approach

    PubMed Central

    Borkotoky, Subhomoi; Meena, Chetan Kumar; Murali, Ayaluru

    2016-01-01

    The single subunit T7 RNA polymerase (T7RNAP) is a model enzyme for studying the transcription process and for various biochemical and biophysical studies. Heparin is a commonly used inhibitor against T7RNAP and other RNA polymerases. However, exact interaction between heparin and T7RNAP is still not completely understood. In this work, we analyzed the binding pattern of heparin by docking heparin and few of its low molecular weight derivatives to T7RNAP, which helps in better understanding of T7RNAP inhibition mechanism. The efficiency of the compounds was calculated by docking the selected compounds and post-docking molecular mechanics/generalized Born surface area analysis. Evaluation of the simulation trajectories and binding free energies of the complexes after simulation showed enoxaparin to be the best among low molecular weight heparins. Binding free energy analysis revealed that van der Waals interactions and polar solvation energy provided the substantial driving force for the binding process. Furthermore, per-residue free energy decomposition analysis revealed that the residues Asp 471, Asp 506, Asp 537, Tyr 571, Met 635, Asp 653, Pro 780, and Asp 812 are important for heparin interaction. Apart from these residues, most favorable contribution in all the three complexes came from Asp 506, Tyr 571, Met 635, Glu 652, and Asp 653, which can be essential for binding of heparin-like structures with T7RNAP. The results obtained from this study will be valuable for the future rational design of novel and potent inhibitors against T7RNAP and related proteins. PMID:27594785

  7. Purification and characterization of a low-molecular-weight acid phosphatase--a phosphotyrosyl-protein phosphatase from bovine heart.

    PubMed

    Zhang, Z Y; Van Etten, R L

    1990-10-01

    A low-molecular-weight acid phosphatase that is representative of a group recently shown to be phosphotyrosyl protein phosphatases was purified to homogeneity from bovine heart. The enzyme was a monomer with a molecular mass of 18 kDa and had an isoelectric point of 7.0. The absorption coefficient, E1% 1cm was 9.65 at 280 nm. The enzyme had pH optima of 5.3 and 6.0 with the substrates p-nitrophenyl phosphate and tyrosine phosphate, respectively. When measured at pH 5 and 37 degrees C, the enzyme had specific activities of 114 and 86 mumol min-1 mg-1 for p-nitrophenyl phosphate and tyrosine O-phosphate, respectively, while the Km values were 0.38 and 14 mM. The enzyme was highly specific for aryl monophosphate esters and showed little or no activity toward aliphatic phosphate esters, with the remarkable exception of flavin mononucleotide (FMN) and certain of its structural analogs. As shown by 31P NMR data, the activity toward FMN was due to the hydrolysis of one of the eight components present in the (commercial) sample. Both molybdate and vanadate were potent inhibitors, with inhibition constants of 37 and 29 microM, respectively; tartrate and fluoride had little effect on enzymatic activity. A two-stage reversible denaturation of the enzyme by guanidine HCl was observed with midpoints of 0.25 and 1.75 M, respectively. The amino acid composition was homologous to the low-molecular-weight acid phosphatases from other tissue. The enzyme showed immunological cross-reactivity against low-molecular-weight human liver acid phosphatase. There were 7 or 8 accessible cysteines on the monomeric protein and at least one was essential for enzyme activity. The enzyme also had phosphotransferase activity, for example transferring phosphate from p-nitrophenyl phosphate to a wide variety of alcohol acceptors.

  8. Synthetic Glycosides and Glycoconjugates of Low Molecular Weight Natural Products.

    PubMed

    Grynkiewicz, G; Szeja, W

    2016-01-01

    Enzymatically controlled transfer of saccharide moieties constitutes a fundamental biological process, essential for both primary and secondary metabolism. Natural products, including countless glycosides, with a rich tradition of use in ethnopharmacology, remain a prime source of inspiration for medicinal chemistry and molecular pharmacology, but their availability from biological sources is usually scarce, hampering attempts at application for new drug discovery and development. Chemical glycosylation on the other hand, although continuously undergoing sophisticated mechanistic studies, has nevertheless already matured as a set of methods which are able to provide substantial amounts of pure chemical entities: natural glycosides, as well as their congeners and mimics, necessary for the study of biological activity in quality assurance systems and required for drug development by pharmaceutical regulations. The paper presents a review of natural products and their analogues glycosylation, in a set of arbitrary selected examples, supplemented with comments on general advances in chemical glycosylation methodology and their applicability for particular categories of secondary metabolites.

  9. Molecular modeling evaluation of non-steroidal aromatase inhibitors.

    PubMed

    Narayana, Bheemanapalli Lakshmi; Pran Kishore, Deb; Balakumar, Chadrasekaran; Rao, Kaki Venkata; Kaur, Rajwinder; Rao, Akkinepally Raghuram; Murthy, Javali Narashima; Ravikumar, Muttineni

    2012-05-01

    A recent discovery of aromatase crystal structure triggered the efforts to design novel aromatase inhibitors for breast cancer therapy. While correlating docking scores with inhibitory potencies of known ligands, feeble robustness of scoring functions toward prediction was observed. This prompted us to develop new prediction models using stepwise regression analysis based on consensus of different docking and their scoring methods (GOLD, LIGANDFIT, and GLIDE). Quantitative structure-activity relationships were developed between the aromatase inhibitory activity (pIC(50) ) of flavonoid derivatives (n=39) and docking scores and docking descriptors. QSAR models have been validated internally [using leave-one-out cross-validated r(2)(cv) (LOO-Q2))] and externally to ensure the predictive capacity of the models. Model 2 [M2] developed using consensus of docking scores of scoring functions viz. ASP, potential of mean force and DOCK Score (r(2)(cv)=0.850, r(2) = 0.870, r(2)(pred) = 0.633, RMSE = 0.363 μm, r(2)(m(test)) =0.831, r(2)(m(overall)) =0.832) was found to be better in predicting aromatase inhibitory potency (pIC(50) ) compared to the Model 1 [M1] based on docking descriptors (r(2)(cv)= 0.848, r(2) = 0.825, r(2)(pred) =0.788, RMSE=0.421μm, r(2)(m(test)) =0.808, r(2)(m(overall)) =0.821). It has been observed that the natural flavonoids and their derivatives were less potent compared to these scaffolds with imidazolylmethyl substitution owing to the interaction of nitrogen atom of the imidazole ring toward the heme (Fe(3+) ) of the aromatase. Results confirm the potential of our methodology for the design of new potent non-steroidal aromatase inhibitors.

  10. A novel dynamic heterogeneous phase polymerization reaction for poly-hemoglobin with narrow molecular weight distribution.

    PubMed

    Wang, Xiang; Huang, Lei; Wang, Jin-Feng; Yang, Cheng-Min

    2008-01-01

    A dynamic heterogeneous phase polymerization reaction is found to be efficient for controllable cross-link of hemoglobin with glutaraldehyde. The selective absorption of the immobile phase and asymmetry of protein concentration leads to narrowness of the molecular weight distribution and lowness of the average molecular weight. Using this method, 53% of hemoglobin obtained is intermolecular cross-linked with 12 molecular equivalents of glutaraldehyde. The majority of poly-hemoglobins is in the range of 128 kD to 258 kD.

  11. Effect of high-speed jet on flow behavior, retrogradation, and molecular weight of rice starch.

    PubMed

    Fu, Zhen; Luo, Shun-Jing; BeMiller, James N; Liu, Wei; Liu, Cheng-Mei

    2015-11-20

    Effects of high-speed jet (HSJ) treatment on flow behavior, retrogradation, and degradation of the molecular structure of indica rice starch were investigated. Decreasing with the number of HSJ treatment passes were the turbidity of pastes (degree of retrogradation), the enthalpy of melting of retrograded rice starch, weight-average molecular weights and weight-average root-mean square radii of gyration of the starch polysaccharides, and the amylopectin peak areas of SEC profiles. The areas of lower-molecular-weight polymers increased. The chain-length distribution was not significantly changed. Pastes of all starch samples exhibited pseudoplastic, shear-thinning behavior. HSJ treatment increased the flow behavior index and decreased the consistency coefficient and viscosity. The data suggested that degradation of amylopectin was mainly involved and that breakdown preferentially occurred in chains between clusters.

  12. Molecular weight changes induced in an anionic polydimethylsiloxane by gamma irradiation in vacuum

    NASA Astrophysics Data System (ADS)

    Satti, Angel J.; Andreucetti, Noemí A.; Ciolino, Andrés E.; Vitale, Cristian; Sarmoria, Claudia; Vallés, Enrique M.

    2010-11-01

    An anionic almost monodisperse linear polydimethylsiloxane (PDMS) was subjected to gamma irradiation under vacuum at room temperature. The molecular weight changes induced by the radiation process have been investigated using size exclusion chromatography (SEC) with refraction index (RI) and multi angle laser light scattering (MALLS) detectors, to obtain the number and weight average molecular weights of the irradiated samples. The analysis of the data indicates that crosslinking reactions predominated over scission reactions. The results obtained by an SEC-RI have confirmed the presence of small, but measurable amounts of scission. A previously developed mathematical model of the irradiation process that accounts for simultaneous scission and crosslinking and allows for both H- and Y-crosslinks, fitted well the measured molecular weight data. This prediction is in accordance with the experimental data obtained by 29Si-Nuclear Magnetic Resonance spectroscopy (NMR) and previously reported data for commercial linear PDMS ( Satti et al., 2008).

  13. Novel Cancer Chemotherapy Hits by Molecular Topology: Dual Akt and Beta-Catenin Inhibitors

    PubMed Central

    Morell, Cecilia; Rodríguez-Henche, Nieves; Recio-Iglesias, Maria Carmen; Garcia-Domenech, Ramon

    2015-01-01

    Background and Purpose Colorectal and prostate cancers are two of the most common types and cause of a high rate of deaths worldwide. Therefore, any strategy to stop or at least slacken the development and progression of malignant cells is an important therapeutic choice. The aim of the present work is the identification of novel cancer chemotherapy agents. Nowadays, many different drug discovery approaches are available, but this paper focuses on Molecular Topology, which has already demonstrated its extraordinary efficacy in this field, particularly in the identification of new hit and lead compounds against cancer. This methodology uses the graph theoretical formalism to numerically characterize molecular structures through the so called topological indices. Once obtained a specific framework, it allows the construction of complex mathematical models that can be used to predict physical, chemical or biological properties of compounds. In addition, Molecular Topology is highly efficient in selecting and designing new hit and lead drugs. According to the aforementioned, Molecular Topology has been applied here for the construction of specific Akt/mTOR and β-catenin inhibition mathematical models in order to identify and select novel antitumor agents. Experimental Approach Based on the results obtained by the selected mathematical models, six novel potential inhibitors of the Akt/mTOR and β-catenin pathways were identified. These compounds were then tested in vitro to confirm their biological activity. Conclusion and Implications Five of the selected compounds, CAS n° 256378-54-8 (Inhibitor n°1), 663203-38-1 (Inhibitor n°2), 247079-73-8 (Inhibitor n°3), 689769-86-6 (Inhibitor n°4) and 431925-096 (Inhibitor n°6) gave positive responses and resulted to be active for Akt/mTOR and/or β-catenin inhibition. This study confirms once again the Molecular Topology’s reliability and efficacy to find out novel drugs in the field of cancer. PMID:25910265

  14. From oligomers to molecular giants of soybean oil in supercritical carbon dioxide medium: 1. Preparation of polymers with lower molecular weight from soybean oil.

    PubMed

    Liu, Zengshe; Sharma, Brajendra K; Erhan, Sevim Z

    2007-01-01

    Polymers with a low molecular weight derived from soybean oil have been prepared in a supercritical carbon dioxide medium by cationic polymerization. Boron trifluoride diethyl etherate was used as an initiator. Influences of polymerization temperature, amount of initiator, and carbon dioxide pressure on the molecular weight were investigated. It is shown that the higher polymerization temperature favors polymers with relatively higher molecular weights. Larger amounts of initiator also provide polymers with higher molecular weights. Higher pressure favors polymers with relatively higher molecular weights. The applications of these soy-based materials will be in the lubrication and hydraulic fluid areas.

  15. Slip of polydisperse polymers: Molecular weight distribution above and below the plane of slip

    NASA Astrophysics Data System (ADS)

    Sabzevari, Seyed Mostafa; Strandman, Satu; Wood-Adams, Paula Marie

    2015-04-01

    When strong slip occurs during the drag flow of highly entangled polybutadienes (PBD) in a sliding plate rheometer equipped with stainless steel parallel plates, a thin film of polymer debris remains on the substrate after the slip. This debris is assumed to be formed by the disentanglement process that occurs in strong slip at a distance of about one molecular size from the plate. In order to evaluate the composition of the debris we collected it with tetrahydrofuran and subjected it to gel permeation chromatography. It was found that the molecular weight distribution (MWD) of the debris is significantly different from that of the bulk. Moreover, in mixtures prepared from long and short PBDs with distinctly different molecular weight distributions, the MWD of the debris was found to be richer in low molecular weight components and leaner in the high molecular weight components compared to the bulk. This information is important since it reveals the compositional difference between the bulk and interfacial layer above and below the plane of slip. The difference in MWD is likely a consequence of the strong slip in which some of long chains are pulled away from the surface-adsorbed chains by the flow leaving a debris lean in the high molecular weight component.

  16. Profiling of the molecular weight and structural isomer abundance of macroalgae-derived phlorotannins.

    PubMed

    Heffernan, Natalie; Brunton, Nigel P; FitzGerald, Richard J; Smyth, Thomas J

    2015-01-16

    Phlorotannins are a group of complex polymers of phloroglucinol (1,3,5-trihydroxybenzene) unique to macroalgae. These phenolic compounds are integral structural components of the cell wall in brown algae, but also play many secondary ecological roles such as protection from UV radiation and defense against grazing. This study employed Ultra Performance Liquid Chromatography (UPLC) with tandem mass spectrometry to investigate isomeric complexity and observed differences in phlorotannins derived from macroalgae harvested off the Irish coast (Fucus serratus, Fucus vesiculosus, Himanthalia elongata and Cystoseira nodicaulis). Antioxidant activity and total phenolic content assays were used as an index for producing phlorotannin fractions, enriched using molecular weight cut-off dialysis with subsequent flash chromatography to profile phlorotannin isomers in these macroalgae. These fractions were profiled using UPLC-MS with multiple reaction monitoring (MRM) and the level of isomerization for specific molecular weight phlorotannins between 3 and 16 monomers were determined. The majority of the low molecular weight (LMW) phlorotannins were found to have a molecular weight range equivalent to 4-12 monomers of phloroglucinol. The level of isomerization within the individual macroalgal species differed, resulting in substantially different numbers of phlorotannin isomers for particular molecular weights. F. vesiculosus had the highest number of isomers of 61 at one specific molecular mass, corresponding to 12 phloroglucinol units (PGUs). These results highlight the complex nature of these extracts and emphasize the challenges involved in structural elucidation of these compounds.

  17. Analyzing the molecular weight distribution in supramolecular polymers.

    PubMed

    Schmid, Stephan A; Abbel, Robert; Schenning, Albertus P H; Meijer, E W; Sijbesma, Rint P; Herz, Laura M

    2009-12-09

    We have investigated the formation process of supramolecular linear polymer chains and its influence on the resulting chain length distribution function. For this purpose, we explored the migration of excitation energy between oligofluorene units coupled together through quadruple hydrogen-bonding groups to form linear chains that are terminated by oligophenylene vinylene end-caps acting as energy traps. The energy transfer dynamics from the main chain to the chain end was monitored experimentally using time-resolved PL spectroscopy and compared to an equivalent Monte Carlo simulation incorporating information on the structure of the chains, the transition transfer rates, and various weight distribution trial functions. We find that the assumption of a Flory distribution of chain lengths leads to excellent agreement between experimental and simulated data for a wide range of end-cap concentrations. On the other hand, both a Poisson function and a simplified assumption of a monodisperse distribution significantly underestimate the presence of long chains in the ensemble. Our results therefore show that supramolecular polymerization is a steplike process equivalent to polycondensation reactions in linear covalent polymers. These findings emphasize that equal reactivity of the supramolecular building blocks leads to a dynamic growth process for the supramolecular chain involving all chain components at all times.

  18. QSAR, molecular docking studies of thiophene and imidazopyridine derivatives as polo-like kinase 1 inhibitors

    NASA Astrophysics Data System (ADS)

    Cao, Shandong

    2012-08-01

    The purpose of the present study was to develop in silico models allowing for a reliable prediction of polo-like kinase inhibitors based on a large diverse dataset of 136 compounds. As an effective method, quantitative structure activity relationship (QSAR) was applied using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The proposed QSAR models showed reasonable predictivity of thiophene analogs (Rcv2=0.533, Rpred2=0.845) and included four molecular descriptors, namely IC3, RDF075m, Mor02m and R4e+. The optimal model for imidazopyridine derivatives (Rcv2=0.776, Rpred2=0.876) was shown to perform good in prediction accuracy, using GATS2m and BEHe1 descriptors. Analysis of the contour maps helped to identify structural requirements for the inhibitors and served as a basis for the design of the next generation of the inhibitor analogues. Docking studies were also employed to position the inhibitors into the polo-like kinase active site to determine the most probable binding mode. These studies may help to understand the factors influencing the binding affinity of chemicals and to develop alternative methods for prescreening and designing of polo-like kinase inhibitors.

  19. Adsorption of dissolved organics in lake water by aluminum oxide. Effect of molecular weight

    USGS Publications Warehouse

    Davis, J.A.; Gloor, R.

    1981-01-01

    Dissolved organic compounds in a Swiss lake were fractionated into three molecular size classes by gel exclusion chromatography, and adsorption of each fraction on colloidal alumina was studied as a function of pH. Organic compounds with molecular weight (Mr) greater than 1000 formed strong complexes with the alumina surface, but low molecular weight compounds were weakly adsorbed. Electrophoretic mobility measurements indicated that alumina particles suspended in the original lake water were highly negatively charged because of adsorbed organic matter. Most of the adsorbed organic compounds were in the Mr range 1000 < Mr < 3000. Adsorption of these compounds during the treatment of drinking water by alum coagulation may be responsible for the preferential removal of trihalomethane precursors. Adsorption may also influence the molecular-weight distribution of dissolved organic material in lakes. surface, the present work will focus on the influence of molecular size and pH on the adsorption behavior of dissolved organic material of a Swiss lake. From a geochemical point of view, it is important to know the molecular-weight distribution of adsorbed organic matter so that we may better assess its reactivity with trace elements. The study also serves as a first step in quantifying the role of adsorption in the geochemical cycle of organic carbon in lacustrine environments. For water-treatment practice, we need to determine whether molecular weight fractionation occurs during adsorption by aluminum oxide. Such a fractionation could be significant in the light of recent reports that chloroform and other organochlorine compounds are preferentially produced by particular molecular-weight fractions (25-27). ?? 1981 American Chemical Society.

  20. Seeking for Non-Zinc-Binding MMP-2 Inhibitors: Synthesis, Biological Evaluation and Molecular Modelling Studies

    PubMed Central

    Ammazzalorso, Alessandra; De Filippis, Barbara; Campestre, Cristina; Laghezza, Antonio; Marrone, Alessandro; Amoroso, Rosa; Tortorella, Paolo; Agamennone, Mariangela

    2016-01-01

    Matrix metalloproteinases (MMPs) are an important family of zinc-containing enzymes with a central role in many physiological and pathological processes. Although several MMP inhibitors have been synthesized over the years, none reached the market because of off-target effects, due to the presence of a zinc binding group in the inhibitor structure. To overcome this problem non-zinc-binding inhibitors (NZIs) have been recently designed. In a previous article, a virtual screening campaign identified some hydroxynaphtyridine and hydroxyquinoline as MMP-2 non-zinc-binding inhibitors. In the present work, simplified analogues of previously-identified hits have been synthesized and tested in enzyme inhibition assays. Docking and molecular dynamics studies were carried out to rationalize the activity data. PMID:27782083

  1. 3D-QSAR, molecular docking and molecular dynamics studies of a series of RORγt inhibitors.

    PubMed

    Wang, Fangfang; Yang, Wei; Shi, Yonghui; Le, Guowei

    2015-09-01

    The discovery of clinically relevant inhibitors of retinoic acid receptor-related orphan receptor-gamma-t (RORγt) for autoimmune diseases therapy has proven to be a challenging task. In the present work, to find out the structural features required for the inhibitory activity, we show for the first time a three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations for a series of novel thiazole/thiophene ketone amides with inhibitory activity at the RORγt receptor. The optimum CoMFA and CoMSIA models, derived from ligand-based superimposition I, exhibit leave-one-out cross-validated correlation coefficient (R(2)cv) of .859 and .805, respectively. Furthermore, the external predictive abilities of the models were evaluated by a test set, producing the predicted correlation coefficient (R(2)pred) of .7317 and .7097, respectively. In addition, molecular docking analysis was applied to explore the binding modes between the inhibitors and the receptor. MD simulation and MM/PBSA method were also employed to study the stability and rationality of the derived conformations, and the binding free energies in detail. The QSAR models and the results of molecular docking, MD simulation, binding free energies corroborate well with each other and further provide insights regarding the development of novel RORγt inhibitors with better activity.

  2. Mucin Agarose Gel Electrophoresis: Western Blotting for High-molecular-weight Glycoproteins.

    PubMed

    Ramsey, Kathryn A; Rushton, Zachary L; Ehre, Camille

    2016-06-14

    Mucins, the heavily-glycosylated proteins lining mucosal surfaces, have evolved as a key component of innate defense by protecting the epithelium against invading pathogens. The main role of these macromolecules is to facilitate particle trapping and clearance while promoting lubrication of the mucosa. During protein synthesis, mucins undergo intense O-glycosylation and multimerization, which dramatically increase the mass and size of these molecules. These post-translational modifications are critical for the viscoelastic properties of mucus. As a result of the complex biochemical and biophysical nature of these molecules, working with mucins provides many challenges that cannot be overcome by conventional protein analysis methods. For instance, their high-molecular-weight prevents electrophoretic migration via regular polyacrylamide gels and their sticky nature causes adhesion to experimental tubing. However, investigating the role of mucins in health (e.g., maintaining mucosal integrity) and disease (e.g., hyperconcentration, mucostasis, cancer) has recently gained interest and mucins are being investigated as a therapeutic target. A better understanding of the production and function of mucin macromolecules may lead to novel pharmaceutical approaches, e.g., inhibitors of mucin granule exocytosis and/or mucolytic agents. Therefore, consistent and reliable protocols to investigate mucin biology are critical for scientific advancement. Here, we describe conventional methods to separate mucin macromolecules by electrophoresis using an agarose gel, transfer protein into nitrocellulose membrane, and detect signal with mucin-specific antibodies as well as infrared fluorescent gel reader. These techniques are widely applicable to determine mucin quantitation, multimerization and to test the effects of pharmacological compounds on mucins.

  3. Resistance mechanism of human immunodeficiency virus type-1 protease to inhibitors: A molecular dynamic approach

    PubMed Central

    Dayer, Mohammad Reza; Dayer, Mohammad Saaid

    2014-01-01

    Human immunodeficiency virus type 1 (HIV-1) protease inhibitors comprise an important class of drugs used in HIV treatments. However, mutations of protease genes accelerated by low fidelity of reverse transcriptase yield drug resistant mutants of reduced affinities for the inhibitors. This problem is considered to be a serious barrier against HIV treatment for the foreseeable future. In this study, molecular dynamic simulation method was used to examine the combinational and additive effects of all known mutations involved in drug resistance against FDA approved inhibitors. Results showed that drug resistant mutations are not randomly distributed along the protease sequence; instead, they are localized on flexible or hot points of the protein chain. Substitution of more hydrophobic residues in flexible points of protease chains tends to increase the folding, lower the flexibility and decrease the active site area of the protease. The reduced affinities of HIV-1 protease for inhibitors seemed to be due to substantial decrease in the size of the active site and flap mobility. A correlation was found between the binding energy of inhibitors and their affinities for each mutant suggesting the distortion of the active site geometry in drug resistance by preventing effective fitting of inhibitors into the enzymes' active site. To overcome the problem of drug resistance of HIV-1 protease, designing inhibitors of variable functional groups and configurations is proposed. PMID:27843989

  4. Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration.

    PubMed

    Barbieri, Davide; Yuan, Huipin; Luo, Xiaoman; Farè, Silvia; Grijpma, Dirk W; de Bruijn, Joost D

    2013-12-01

    In bone tissue regeneration, certain polymer and calcium-phosphate-based composites have been reported to enhance some biological surface phenomena, facilitating osteoinduction. Although the crucial role of inorganic fillers in heterotopic bone formation by such materials has been shown, no reports have been published on the potential effects the polymer phase may have. The present work starts from the assumption that the polymer molecular weight regulates the fluid uptake, which determines the hydrolysis rate and the occurrence of biological surface processes. Here, two composites were prepared by extruding two different molecular weight L/D,L-lactide copolymers with calcium phosphate apatite. The lower molecular weight copolymer allowed larger fluid uptake in the composite thereof, which was correlated with a higher capacity to adsorb proteins in vitro. Further, the large fluid absorption led to a quicker composite degradation that generated rougher surfaces and enhanced ion release. Following intramuscular implantation in sheep, only the composite with the lower molecular weight polymer could induce heterotopic bone formation. Besides influencing the biological potential of composites, the molecular weight also regulated their viscoelastic behaviour under cyclic stresses. The results lead to the conclusion that designing biomaterials with appropriate physico-chemical characteristics is crucial for bone tissue regeneration in mechanical load-bearing sites.

  5. Anticancer properties of low molecular weight oat beta-glucan – An in vitro study.

    PubMed

    Choromanska, Anna; Kulbacka, Julita; Rembialkowska, Nina; Pilat, Justyna; Oledzki, Remigiusz; Harasym, Joanna; Saczko, Jolanta

    2015-09-01

    Anticancer properties of 1-3, 1-4 oat beta glucan are under intensive investigation now. Antitumor characteristic of fungi and yeast beta-glucans have been widely recognized, but those polysaccharides are mostly insoluble which creates several problems especially in topical formulation. Also high molecular weight oat beta-glucans reveal high viscosity which restricts its application. According to those problems in the current study the antitumor activities of low molecular weight beta-glucan derived from oats were investigated in cancer cells: Me45, A431 and normal HaCaT and murine macrophages P388/D1. The low molecular weight beta-glucan from oat significantly deceased cancer cells viability, while for the normal cells it was non-toxic. It was observed that with the increasing incubation time and the beta-glucan concentration the cancer cells viability significantly deceased. Furthermore for the normal cells the low molecular weight beta-glucan from oat was non-toxic. Immunocytochemical ABC analysis showed that beta-glucan induced strong expression of caspase-12 in both cancer cell lines, while in HaCaT cells ABC reaction was significantly lower and in P388/D1 cell line ABC reaction was negative. Our preliminary studies show strong anti-tumor properties of new low molecular weight beta-glucan from oat and at the same time no toxicity for normal cells.

  6. Media optimization for elevated molecular weight and mass production of pigment-free pullulan.

    PubMed

    Yu, Xiaoliu; Wang, Yulei; Wei, Gongyuan; Dong, Yingying

    2012-07-01

    In this study, an Aureobasidium pullulans SZU 1001 mutant, deficient in pigment production, was screened by complex UV and γ-ray mutagenesis. Medium composition optimization for increased pullulan molecular weight and production was conducted using this mutant. Six nutrients: yeast extract, (NH4)2SO4, K2HPO4, NaCl, MgSO4·7H2O and CaCl2 were detected within pullulan production in flasks. It is shown that NaCl and K2HPO4 have significant influences on molecular weight of pullulan, while yeast extract and (NH4)2SO4 significantly affect pullulan yield. To achieve a higher molecular weight and more efficient pullulan production, a response surface methodology approach was introduced to predict an optimal nutrient combination. A molecular weight of 5.74 × 10(6) and pullulan yield on glucose of 51.30% were obtained under batch pullulan fermentation with the optimized media, which increased molecular weight and pullulan production by 97.25% and 11.04%, respectively compared with the control media.

  7. The effect of molecular weight on the material properties of biosynthesized poly(4-hydroxybutyrate).

    PubMed

    Boesel, Luciano F; Le Meur, Sylvaine; Thöny-Meyer, Linda; Ren, Qun

    2014-11-01

    Poly(4-hydroxybutyrate) (P4HB) is a bacterial polyhydroxyalkanoate with interesting biological and physico-chemical properties for the use in biomedical applications. The synthesis of P4HB through a fermentation process often leads to a polymer with a too high molecular weight, making it difficult to process it further by solvent- or melt-processing. In this work P4HB was degraded to obtain polymers with a molecular weight ranging from 1.5×10(3)g/mol to 1.0×10(6)g/mol by using a method established in our laboratory. We studied the effect of the change in molecular weight on thermal and mechanical properties. The decrease of the molecular weight led to an increase in the degree of crystallinity of the polymer. Regarding the tensile mechanical properties, the molecular weight played a more prominent role than the degree of crystallinity in the evolution of the properties for the different polymer fractions. The method presented herein allows the preparation of polymer fractions with easier processability and still adequate thermal and mechanical properties for biomedical applications.

  8. Raoult's law-based method for determination of coal tar average molecular weight

    SciTech Connect

    Brown, D.G.; Gupta, L.; Horace, H.K.; Coleman, A.J.

    2005-08-01

    A Raoult's law-based method for determining the number average molecular weight of coal tars is presented. The method requires data from two-phase coal tar/water equilibrium experiments, which readily are performed in environmental laboratories. An advantage of this method for environmental samples is that it is not impacted by the small amount of inert debris often present in coal tar samples obtained from contaminated sites. Results are presented for 10 coal tars from nine former manufactured gas plants located in the eastern United States. Vapor pressure osmometry (VPO) analysis provided similar average molecular weights to those determined with the Raoult's law-based method, except for one highly viscous coal tar sample. Use of the VPO-based average molecular weight for this coal tar resulted in underprediction of the coal tar constituents' aqueous concentrations. Additionally, one other coal tar was not completely soluble in solvents used for VPO analysis. The results indicate that the Raoult's law-based method is able to provide an average molecular weight that is consistent with the intended application of the data (e.g., modeling the dissolution of coal tar constituents into surrounding waters), and this method can be applied to coal tars that may be incompatible with other commonly used methods for determining average molecular weight, such as vapor pressure osmometry.

  9. Low molecular weight hyaluronic acid prevents oxygen free radical damage to granulation tissue during wound healing.

    PubMed

    Trabucchi, E; Pallotta, S; Morini, M; Corsi, F; Franceschini, R; Casiraghi, A; Pravettoni, A; Foschi, D; Minghetti, P

    2002-01-01

    Hyaluronic acid protects granulation tissue from oxygen free radical damage and stimulates wound healing, but its molecular weight prevents it from permeating the epidermal barrier A low molecular weight hyaluronic acid preparation is able to permeate the skin, but it is unknown whether or not it retains the scavenging effects of oxygen free radicals in granulation tissue. Our experiments were conducted in rats with excisional or incisional wounds. Wound contraction over 11 days and breaking strength on the fifth day were measured. Oxygen free radical production was induced by intraperitoneal administration of two different xenobiotics: phenazine methosulfate and zymosan. The wounds were treated topically with low molecular weight hyaluronic acid (0.2%) cream or placebo. In the incisional wound group, the effects of superoxide dismutase were also determined. Absolute controls received wounds and placebo but no xenobiotics. Wound healing was significantly slower in the xenobiotic group than in the control groups. These effects were strongly reduced by topical administration of low molecular weight hyaluronic acid (0.2%) cream and in incisional wounds by topically injected superoxide dismutase. Low molecular weight hyaluronic acid is effective as the native compound against oxygen free radicals. Its pharmacological effects through transdermal administration should be tested in appropriate models.

  10. Bioactivity of Variant Molecular Weight Chitosan Against Drug-Resistant Bacteria Isolated from Human Wounds.

    PubMed

    Bano, Ijaz; Arshad, Muhammad; Ghauri, Muhammad Afzal; Yasin, Tariq; Younus, Muhammad

    2017-03-30

    Chitosan available from crab shells is usually of high molecular weight which may result in reduced efficiency for its antibacterial activity. One of the techniques for improving chitosan antibacterial efficiency is reducing its molecular weight. The irradiation of chitosan by gamma radiations is considered to be one of the most effective and widely used methods for improving its antibacterial activity. Chitosan obtained from crab shells was irradiated with gamma radiations at different doses, and effects on chitosan were analyzed by molecular weight determination and Fourier Transform Infrared spectroscopy. Unirradiated and irradiated chitosans were studied for their antibacterial properties against bacterial pathogens, that is, Pseudomonas aeruginosa (SS29), Escherichia coli (SS2, SS9), Proteus mirabilis (SS77), and Staphylococcus aureus (LM15). Studies have shown that irradiation has significantly developed and improved the antibacterial activity of crab shell chitosan. A correlation was found between bacterial metabolites and antibacterial activity by the analysis for 4-hydroxy-2-alkylquinolines and related metabolites of P. aeruginosa (SS29) in the absence and presence of chitosan by liquid chromatography mass spectrometer, exhibiting the suppression of these virulence factors due to chitosan. Antibacterial efficiency of chitosan was found to be molecular weight dependent and applied concentration of the chitosan. The findings suggest on the use of low-molecular weight chitosan as antibacterial agent in pharmaceutical preparations.

  11. Effect of molecular weight of dissolved organic matter on toxicity and bioavailability of copper to lettuce.

    PubMed

    Wang, Xudong; Chen, Xianni; Liu, Shuai; Ge, Xizu

    2010-01-01

    To clarify the effects of molecular weight of dissolved organic matter (DOM) on the toxicity and bioavailability of copper (Cu) to plants, DOM extracted from chicken manure was ultra-filtered into four fractions according to their molecular weights by means of sequential-stage ultrafiltration technique. Lettuce seeds were germinated by being exposed to the solutions containing Cu2+ with or without different fractions of DOM. The concentration of copper in roots, leaves, sprouts and the length of roots were investigated. The results showed that not all fractions of DOM could improve copper availability or toxicity. The fraction of DOM with larger molecular weight more than 1 kDa had higher complexation stability with Cu2+ and caused lower concentration of free Cu2+ ion in the solution of copper plus the fraction, resulting in lower availability and toxicity of copper to lettuce, but the fraction with molecular weight less than 1 kDa had the opposite function. Therefore, the molecular weight of 1 kDa may be the division point to determine DOM to increase or decrease copper availability and toxicity.

  12. Complete Molecular Weight Profiling of Low-Molecular Weight Heparins Using Size Exclusion Chromatography-Ion Suppressor-High-Resolution Mass Spectrometry.

    PubMed

    Zaia, Joseph; Khatri, Kshitij; Klein, Joshua; Shao, Chun; Sheng, Yuewei; Viner, Rosa

    2016-11-01

    Low-molecular weight heparins (LMWH) prepared by partial depolymerization of unfractionated heparin are used globally to treat coagulation disorders on an outpatient basis. Patent protection for several LMWH has expired and abbreviated new drug applications have been approved by the Food and Drug Administration. As a result, reverse engineering of LMWH for biosimilar LMWH has become an active global endeavor. Traditionally, the molecular weight distributions of LMWH preparations have been determined using size exclusion chromatography (SEC) with optical detection. Recent advances in liquid chromatography-mass spectrometry methods have enabled exact mass measurements of heparin saccharides roughly up to degree-of-polymerization 20, leaving the high molecular weight half of the LMWH preparation unassigned. We demonstrate a new LC-MS system capable of determining the exact masses of complete LMWH preparations, up to dp30. This system employed an ion suppressor cell to desalt the chromatographic effluent online prior to the electrospray mass spectrometry source. We expect this new capability will impact the ability to define LMWH mixtures favorably.

  13. Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies

    PubMed Central

    Mazumder, Mohit; Das, Umashankar; Gourinath, Samudrala

    2017-01-01

    Peroxisome proliferator-activated receptor gamma (PPARγ) is a potential target for the treatment of several disorders. In view of several FDA approved kinase inhibitors, in the current study, we have investigated the interaction of selected kinase inhibitors with PPARγ using computational modeling, docking, and molecular dynamics simulations (MDS). The docked conformations and MDS studies suggest that the selected KIs interact with PPARγ in the ligand binding domain (LBD) with high positive predictive values. Hence, we have for the first time shown the plausible binding of KIs in the PPARγ ligand binding site. The results obtained from these in silico investigations warrant further evaluation of kinase inhibitors as PPARγ ligands in vitro and in vivo. PMID:28321247

  14. The Role of Molecular Weight and Temperature on the Elastic and Viscoelastic Properties of a Glassy Thermoplastic Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2001-01-01

    Mechanical testing of the elastic and viscoelastic response of an advanced thermoplastic polyimide (LaRC-SI) with known variations in molecular weight was performed over a range of temperatures below the glass transition temperature. The notched tensile strength was shown to be a strong function of both molecular weight and temperature, whereas stiffness was only a strong function of temperature. A critical molecular weight was observed to occur at a weight average molecular weight of M, approx. 22,000 g/mol below which, the notched tensile strength decreases rapidly. This critical molecular weight transition is temperature-independent. Low, molecular weight materials tended to fail in a brittle manner, whereas high molecular weight materials exhibited ductile failure. Furthermore, low molecular weight materials have increased creep compliance and creep compliance rate, and are more sensitive to temperature than the high molecular weight materials. At long timescales (less than 1100 hours) physical aging serves to significantly decrease the creep compliance and creep rate of all the materials tested. Low molecular weight materials are less influenced by the effects of physical aging.

  15. Application of computer-assisted molecular modeling (CAMM) for immunoassay of low molecular weight food contaminants: A review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunoassay for low molecular weight food contaminants, such as pesticides, veterinary drugs, and mycotoxins is now a well-established technique which meets the demands for a rapid, reliable, and cost-effective analytical method. However, due to limited understanding of the fundamental aspects of i...

  16. Review of bemiparin sodium--a new second-generation low molecular weight heparin and its applications in venous thromboembolism.

    PubMed

    Planès, Andre

    2003-09-01

    Bemiparin sodium (Hibor, Ivor, Zivor, Badyket, Laboratorios Farmaceuticos Rovi SA) is a new second-generation low molecular weight heparin (LMWH). Bemiparin has the lowest mean molecular weight (3600 Da), the longest half-life (5.3 h) and the largest antifactor Xa:antifactor IIa ratio (8:1) of all LMWHs. Bemiparin promotes a greater release of tissue factor pathway inhibitor than unfractionated heparin (UFH) or dalteparin. These properties could result in a more favourable efficacy:safety ratio than the currently marketed LMWHs. Bemiparin 2500 IU/day was as effective as UFH for preventing venous thromboembolism (VTE) in moderate risk abdominal surgery. Bemiparin 3500 IU/day significantly reduced VTE compared to UFH in high-risk hip replacement surgery. Bemiparin 3500 IU/day started postoperatively was as effective as enoxaparin 4000 IU/day started preoperatively in total knee arthroplasty, with a trend towards a lower rate of proximal deep vein thrombosis (DVT), pulmonary embolism and symptomatic VTE. In patients with acute DVT, bemiparin was more effective than UFH in thrombus mass reduction and at least as effective as UFH for the prevention of clinical recurrence. Bemiparin was as effective as UFH for clot prevention during haemodialysis. The use of bemiparin was associated with a lower incidence of major and minor bleeding as compared to UFH in abdominal surgery. When compared with enoxaparin in orthopaedic surgery, a lower rate of complications at injection site was observed.

  17. The antineoplastic effect of low-molecular-weight heparins – a literature review

    PubMed Central

    Püsküllüoğlu, Mirosława; Krzemieniecki, Krzysztof

    2013-01-01

    There is some evidence for the antitumor effect of heparins, especially the low-molecular-weight ones. The authors discuss the potential mechanism of this antineoplastic effect and present results from several in vitro and in vivo experiments. The clinical trials concerning the impact of low-molecular-weight heparins on the tumor and on the patients’ survival are described. The objective was to find out if heparins could be administered as an antitumor drug, independently of their anticoagulatory properties. The antitumor role of tissue factor, heparinase, chemokines, stromal proteins, cellular interactions as well as angiogenesis and immunology seems certain. The results of the available studies seem promising but large clinical trials are necessary in order to confirm the antineoplastic effect of the low-molecular-weight heparins and to approve them for standard anticancer treatment. It could be a breakthrough in modern oncology. PMID:23788954

  18. Determination of the presence of hyaluronic acid in preparations containing amino acids: the molecular weight characterization.

    PubMed

    Bellomaria, A; Nepravishta, R; Mazzanti, U; Marchetti, M; Piccioli, P; Paci, M

    2014-10-15

    Several pharmaceutical preparations contain hyaluronic acid in the presence of a large variety of low molecular weight charged molecules like amino acids. In these mixtures, it is particularly difficult to determine the concentration and the molecular weight of the hyaluronic acid fragments. In fact zwitterionic compounds in high concentration behave by masking the hyaluronic acid due to the electrostatic interactions between amino acids and hyaluronic acid. In such conditions the common colorimetric test of the hyaluronic acid determination appears ineffective and in the (1)H NMR spectra the peaks of the polymer disappear completely. By a simple separation procedure the presence of hyaluronic acid was revealed by the DMAB test and (1)H NMR while its average molecular weight in the final product was determined by DOSY NMR spectroscopy alone. The latter determination is very important due to the healthy effects of some sizes of this polymer's fragments.

  19. Characteristics and bioactivities of different molecular weight polysaccharides from camellia seed cake.

    PubMed

    Xu, Zhou; Li, Xu; Feng, Shiling; Liu, Jing; Zhou, Lijun; Yuan, Ming; Ding, Chunbang

    2016-10-01

    Four polysaccharides, namely COP-1, COP-2, COP-3 and COP-4, were ultrafiltrated from crud Camellia oleifera seed cake polysaccharides (COP-c), purified, and characterized, including the determination of antioxidant and antiproliferative activities. Their molecular weights were 7.9, 36, 83 and 225kDa, respectively. All COPs showed the similar FT-IR spectrums, but significant differentials in monosaccharide components. COP-2 exhibited the highest radical scavenging abilities. COP-1 has the strongest metal chelating capabilities. Although with higher molecular weight, COP-4 showed the poorest antioxidant abilities. These results suggested appreciate molecular weight COP possessed a better antioxidant activities. Additionally, all COPs had non-significant antiproliferative abilities in HaLa and HepG2 cells.

  20. Low molecular-weight phenols in Tannat wines made by alternative winemaking procedures.

    PubMed

    Favre, Guzmán; Peña-Neira, Álvaro; Baldi, Cecilia; Hernández, Natalia; Traverso, Sofía; Gil, Graciela; González-Neves, Gustavo

    2014-09-01

    Low molecular weight phenols of Tannat red wines produced by Traditional Maceration (TM), Prefermentative Cold Maceration (PCM), Maceration Enzyme (ENZ) and grape-Seed Tannins additions (ST), were performed and discussed. Alternatives to TM increased wine phenolic contents but unequally, ST increased mainly smaller flavans-3-ol, PCM anthocyanins and ENZ proanthocyanidins (up to 2250 mg/L). However low molecular weight flavan-3-ols remained below 9 mg/L in all wines, showing that there is not necessarily a correspondence between wine richness in total tannins and flavan-3-ols contents at low molecular weight. PCM wines had particularly high concentrations of tyrosol and tryptophol, yeast metabolism derived compounds. The use of grape-seed enological tannins did not increase grape seed derived phenolic compounds such as gallic acid. Caftaric acid was found in concentrations much higher than those reported in other grape varieties. Wine phenolic content and composition was considerably affected by the winemaking procedures tested.

  1. Pharmacological effects and clinical applications of ultra low molecular weight heparins.

    PubMed

    Liu, Zhang; Ji, Shengli; Sheng, Juzheng; Wang, Fengshan

    2014-02-01

    Heparin, one of the common anticoagulants, is clinically used to prevent and treat venous thromboembolism (VTE). Though it has been the drug of choice for many advanced medical and surgical procedures with a long history, the adverse events, such as bleeding, heparin-induced thrombocytopenia (HIT), allergic reactions, follow. Therefore, low molecular weight heparins (LMWHs) and ultra low molecular weight heparins (ULMWHs), with lower molecular weights, higher anti-FXa activity, longer half-life times and lower incidence of adverse events than unfractionated heparin (UFH), were researched and developed. Fondaparinux, a chemically synthesized ULMWH of pentasaccharide, has the same antithrombin III (AT-III)-binding sequence as found in UFH and LMWH. In addition, AVE5026 and RO-14, another two ULMWHs, are obtained by selective chemical depolymerization. In this paper, we review the preparation process, pharmacological effects and clinical applications of fondaparinux, AVE5026 and RO-14.

  2. The development of low-molecular weight hydrogels for applications in cancer therapy

    NASA Astrophysics Data System (ADS)

    Tian, Ran; Chen, Jin; Niu, Runfang

    2014-03-01

    To improve the anti-cancer efficacy and to counteract the side effects of chemotherapy, a variety of drug delivery systems have been invented in past decades, but few of these systems have succeeded in clinical trials due to their respective inherent shortcomings. Recently, low-molecular weight hydrogels of peptides that self-assemble via non-covalent interactions have attracted considerable attention due to their good biocompatibility, low toxicity, inherent biodegradability as well as their convenience of design. Low-molecular weight hydrogels have already shown promise in biomedical applications as diverse as 3D-cell culture, enzyme immobilization, controllable MSC differentiation, wound healing, drug delivery etc. Here we review the recent development in the use of low-molecular weight hydrogels for cancer therapy, which may be helpful in the design of soft materials for drug delivery.

  3. Low molecular weight chitosan-insulin polyelectrolyte complex: characterization and stability studies.

    PubMed

    Al-Kurdi, Zakieh I; Chowdhry, Babur Z; Leharne, Stephen A; Al Omari, Mahmoud M H; Badwan, Adnan A

    2015-03-30

    The aim of the work reported herein was to investigate the effect of various low molecular weight chitosans (LMWCs) on the stability of insulin using USP HPLC methods. Insulin was found to be stable in a polyelectrolyte complex (PEC) consisting of insulin and LMWC in the presence of a Tris-buffer at pH 6.5. In the presence of LMWC, the stability of insulin increased with decreasing molecular weight of LMWC; 13 kDa LMWC was the most efficient molecular weight for enhancing the physical and chemical stability of insulin. Solubilization of insulin-LMWC polyelectrolyte complex (I-LMWC PEC) in a reverse micelle (RM) system, administered to diabetic rats, results in an oral delivery system for insulin with acceptable bioactivity.

  4. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    PubMed

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes.

  5. Influence of refractive index and molecular weight of alcohol agents on skin optical clearing effect

    NASA Astrophysics Data System (ADS)

    Mao, Zhongzhen; Zheng, Ying; Hu, Yating; Lu, Wei; Luo, Qingming; Zhu, Dan

    2007-02-01

    In order to discuss the relative factors affecting the optical clearing effect of agents on skin tissues, six hydroxy-terminated and saturated alcohols with different refractive index and molecular weight were chosen as the optical clearing agents (OCAs). After being treated by different OCAs, the change of transmitted intensity of porcine skins in vitro was measured by single integrating sphere system. The results showed the optical clearing effects of six OCAs, i.e., glycerol, PEG400, PEG200, 1,3-propylene glycol, 1,4-butanediol and 1-butanol, arranged in the descending order. Based on the above results, the refractive index and molecular weight was further discussed. The optical clearing effect of alcohols has been deduced to have negative correlation with refractive index (r=-0.608), but no correlation with molecular weight (r= 0.008).

  6. Properties of different molecular weight sodium lignosulfonate fractions as dispersant of coal-water slurry

    SciTech Connect

    Zhou, M.S.; Qiu, X.Q.; Yang, D.J.; Lou, H.M.

    2006-07-01

    Four purified sodium lignosulfonate (SL) samples with different molecular weights were prepared by fractionation using ultrafiltration. The effect of the molecular weights of SL on the apparent viscosity of coal-water slurry (CWS) was investigated by studying the adsorption amounts and the zeta potentials in the coal-water interface. The results show that the adsorption behavior of the dispersants in the coal-water interface is the key factor to affect the dispersing effect, that the higher adsorption amount and compact adsorption film help reduce the viscosity reduction of CWS, and that the zeta potential is also an important factor influenced by the sulfonic group and carboxy contents of the lignosulfonate molecule. Furthermore, SL with a molecular weight ranging from 10000 to 50000 has both a higher adsorbed amount and zeta potential on the coal surface and the best effect on reducing the viscosity of the coal-water slurry.

  7. Supramolecular star polymers. Increased molecular weight with decreased polydispersity through self-assembly.

    PubMed

    Todd, Eric M; Zimmerman, Steven C

    2007-11-28

    A ditopic structure containing two heterocyclic DeAP units and programmed to self-assemble is used as an initiation unit for the synthesis of polylactide and polystyrene. The resultant polymers self-assemble into higher molecular weight structures with a lower molecular weight distribution. The largest discrete nanoscale polymeric assembly is proposed to be a hexameric star with a molecular weight of ca. 92.7 kDa. All polymeric assemblies generally exhibit PDI values of 1.3 to 1.5, which are lower than the PDI value of the corresponding polymeric arms. A hexameric assembly is stabilized by 30 hydrogen bonds, including six AADD.DDAA contacts. The hexameric star is formed under conditions that are at least partially controlled by kinetics.

  8. Rapid analysis of acylglycerols in low molecular weight milk fat fractions.

    PubMed

    Craven, R J; Lencki, R W

    2007-05-01

    A suitable analytical method was required to facilitate development of an industrial-scale short-path distillation (SPD) process. Short-path distillation produces milk fat distillates (MFD) enriched in low molecular weight milk fat components-viz. free fatty acids, monoacylglycerols, diacylglycerols, cholesterol and low molecular weight triacylglycerols. In this case, solid-phase extraction (SPE) was considered a better alternative than thin-layer chromatography for separating polar and apolar lipid components in MFD samples due to its speed and near-complete recoveries. Solid-phase extraction of MFDs yielded two fractions, both of which are sufficiently pure for subsequent analysis by gas chromatography. This procedure provided rapid and complete chemical characterization (including mass balances) of low-molecular weight milk-fat fractions.

  9. Synthetic polycations with controlled charge density and molecular weight as building blocks for biomaterials.

    PubMed

    Kleinberger, Rachelle M; Burke, Nicholas A D; Zhou, Christal; Stöver, Harald D H

    2016-01-01

    A series of polycations prepared by RAFT copolymerization of N-(3-aminopropyl)methacrylamide hydrochloride (APM) and N-(2-hydroxypropyl)methacrylamide, with molecular weights of 15 and 40 kDa, and APM content of 10-75 mol%, were tested as building blocks for electrostatically assembled hydrogels such as those used for cell encapsulation. Complexation and distribution of these copolymers within anionic calcium alginate gels, as well as cytotoxicity, cell attachment, and cell proliferation on surfaces grafted with the copolymers were found to depend on composition and molecular weight. Copolymers with lower cationic charge density and lower molecular weight showed less cytotoxicity and cell adhesion, and were more mobile within alginate gels. These findings aid in designing improved polyelectrolyte complexes for use as biomaterials.

  10. Synthesis, characterization, and controlled release of selenium nanoparticles stabilized by chitosan of different molecular weights.

    PubMed

    Zhang, Chunyue; Zhai, Xiaona; Zhao, Guanghua; Ren, Fazheng; Leng, Xiaojing

    2015-12-10

    Chitosan-stabilized selenium nanoparticles (SeNPs) have been reported, but there is no information on the effect of the chitosan molecular weight on the structure, stability, and selenium release properties of the SeNPs. Herein, we compared the uniform Se(0) spherical nanoparticles prepared through the reduction of seleninic acid with ascorbic acid in the presence of chitosan with different molecular weights (Mws). We found that both low and high molecular weight chitosan-stabilized selenium nanoparticles exhibited core-shell microstructures with a size of about 103 nm after 30 days growing through the "bottom-up approach" and "top-down approach," respectively. Moreover, both chitosan SeNPs processed excellent stability towards pH and enzyme treatment. In contrast, selenium was easily released to different extents from these two chitosan SeNPs upon treatment with different free radicals. This makes these materials potentially useful as oral antioxidant supplements.

  11. A log-normal distribution model for the molecular weight of aquatic fulvic acids

    USGS Publications Warehouse

    Cabaniss, S.E.; Zhou, Q.; Maurice, P.A.; Chin, Y.-P.; Aiken, G.R.

    2000-01-01

    The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a lognormal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured M(n) and M(w) and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several types of molecular weight data, including the shapes of high- pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.The molecular weight of humic substances influences their proton and metal binding, organic pollutant partitioning, adsorption onto minerals and activated carbon, and behavior during water treatment. We propose a log-normal model for the molecular weight distribution in aquatic fulvic acids to provide a conceptual framework for studying these size effects. The normal curve mean and standard deviation are readily calculated from measured Mn and Mw and vary from 2.7 to 3 for the means and from 0.28 to 0.37 for the standard deviations for typical aquatic fulvic acids. The model is consistent with several type's of molecular weight data, including the shapes of high-pressure size-exclusion chromatography (HP-SEC) peaks. Applications of the model to electrostatic interactions, pollutant solubilization, and adsorption are explored in illustrative calculations.

  12. Molecular weight effects upon the adhesive bonding of a mussel mimetic polymer.

    PubMed

    Jenkins, Courtney L; Meredith, Heather J; Wilker, Jonathan J

    2013-06-12

    Characterization of marine biological adhesives are teaching us how nature makes materials and providing new ideas for synthetic systems. One of the most widely studied adhering animals is the marine mussel. This mollusk bonds to wet rocks by producing an adhesive from cross-linked proteins. Several laboratories are now making synthetic mimics of mussel adhesive proteins, with 3,4-dihydroxyphenylalanine (DOPA) or similar molecules pendant from polymer chains. In select cases, appreciable bulk bonding results, with strengths as high as commercial glues. Polymer molecular weight is amongst several parameters that need to be examined in order to both understand biomimetic adhesion as well as to maximize performance. Experiments presented here explore how the bulk adhesion of a mussel mimetic polymer varies as a function of molecular weight. Systematic structure-function studies were carried out both with and without the presence of an oxidative cross-linker. Without cross-linking, higher molecular weights generally afforded higher adhesion. When a [N(C4H9)4](IO4) cross-linker was added, adhesion peaked at molecular weights of ~50,000-65,000 g/mol. These data help to illustrate how changes to the balance of cohesion versus adhesion influence bulk bonding. Mussel adhesive plaques achieve this balance by incorporating several proteins with molecular weights ranging from 6000 to 110,000 g/mol. To mimic these varied proteins we made a blend of polymers containing a range of molecular weights. Interestingly, this blend adhered more strongly than any of the individual polymers when cross-linked with [N(C4H9)4](IO4). These results are helping us to both understand the origins of biological materials as well as design high performance polymers.

  13. In vitro synthesis of high molecular weight rubber by Hevea small rubber particles.

    PubMed

    Rojruthai, Porntip; Sakdapipanich, Jitladda Tangpakdee; Takahashi, Seiji; Hyegin, Lee; Noike, Motoyoshi; Koyama, Tanetoshi; Tanaka, Yasuyuki

    2010-02-01

    Hevea brasiliensis is one of few higher plants producing the commercial natural rubber used in many significant applications. The biosynthesis of high molecular weight rubber molecules by the higher plants has not been clarified yet. Here, the in vitro rubber biosynthesis was performed by using enzymatically active small rubber particles (SRP) from Hevea. The mechanism of the in vitro rubber synthesis was investigated by the molecular weight distribution (MWD). The highly purified SRP prepared by gel filtration and centrifugation in the presence of Triton((R)) X-100 showed the low isopentenyl diphosphate (IPP) incorporation for the chain extension mechanism of pre-existing rubber. The MWD of in vitro rubber elongated from the pre-existing rubber chains in SRP was analyzed for the first time in the case of H. brasiliensis by incubating without the addition of any initiator. The rubber transferase activity of 70% incorporation of the added IPP (w/w) was obtained when farnesyl diphosphate was present as the allylic diphosphate initiator. The in vitro synthesized rubber showed a typical bimodal MWD of high and low molecular weight fractions in GPC analysis, which was similar to that of the in vivo rubber with peaks at around 10(6) and 10(5) Da or lower. The reaction time independence and dependence of molecular weight of high and low molecular weight fractions, respectively, indicated that the high molecular weight rubber was synthesized from the chain extension of pre-existing rubber molecules whereas the lower one was from the chain elongation of rubber molecules newly synthesized from the added allylic substrates.

  14. In vitro studies of PEG thin films with different molecular weights deposited by MAPLE

    NASA Astrophysics Data System (ADS)

    Paun, Irina Alexandra; Ion, Valentin; Luculescu, Catalin-Romeo; Dinescu, Maria; Canulescu, Stela; Schou, Jørgen

    2012-10-01

    In this work, polyethylene glycol (PEG) films were produced by Matrix Assisted Pulsed Laser Evaporation (MAPLE). The possibility to tailor the properties of the films by means of polymer molecular weight was explored. The films of PEG of average molecular weights 400 Da, 1450 Da, and 10000 Da (PEG400, PEG1450, and PEG10000) were investigated in vitro, in media similar with those inside the body (phosphate buffer saline PBS with pH 7.4 and blood). The mass of the polymer did not change during this treatment, but the polymer molecular weight was found to strongly influence the films properties and their behavior in vitro. Thus, immersion in PBS induced swelling of the PEG films, which was more pronounced for PEG polymers of higher molecular weight. Prior to immersion in PBS, the PEG films of higher molecular weight were more hydrophilic, the water contact angles decreasing from ˜66 grd for PEG400 to ˜41 grd for PEG1450 and to ˜15 grd for PEG10000. The same trend was observed during immersion of the PEG films in PBS. Before immersion in PBS, the refractive index of the films increased from ˜1.43 for PEG400 to ˜1.48 for PEG1450 and to ˜1.68 for PEG10000. During immersion in PBS the refractive index decreased gradually, but remained higher for the PEG molecules of higher mass. Finally, blood compatibility tests showed that the PEG films of higher molecular weight were most compatible with blood.

  15. Biocompatibility of low molecular weight polymers for two-phase partitioning bioreactors.

    PubMed

    Harris, Jesse; Daugulis, Andrew J

    2015-12-01

    Two phase partitioning bioreactors (TPPBs) improve the efficiency of fermentative processes by limiting the exposure of microorganisms to toxic solutes by sequestering them into a non-aqueous phase (NAP). A potential limitation of this technology, when using immiscible organic solvents as the NAP, is the cytoxicity that these materials may exert on the microbes. An improved TPPB configuration is one in which polymeric NAPs are used to replace organic solvents in order to take advantage of their low cost, improved handling qualities, and biocompatibility. A recent study has shown that low molecular weight polymers may confer improved solute uptake relative to high molecular weight polymers (i.e., have higher partition coefficients), but it is unknown whether sufficiently low molecular weight polymers may inhibit cell growth. This study has investigated the biocompatibility of a range of low molecular weight polymers, and compared trends in biocompatibility to the well-established "critical log P" concept. This was achieved by determining the biocompatibility of polypropylene glycol polymers over a molecular weight (MW) range of 425-4,000 to Saccharomyces cerevisiae and Pseudomonas putida, two organisms which have been previously used in TPPB systems. The lower MW polymers were shown to have lower average log P values, and showed more cytotoxicity than polymers of the same structure but with higher molecular weight. Since polymers are generally polydisperse (i.e., polymer samples contain a distribution of MWs), removal of the lower MW fractions via water washing was found to result in improved polymer biocompatibility. These results suggest that the critical log P concept remains useful for describing the toxicity of polymeric substances of different MWs, although it is complicated by the presence of the low MW fractions in the polymers arising from polydispersity.

  16. Increasing the wear resistance of ultra-high molecular weight polyethylene by adding solid lubricating fillers

    SciTech Connect

    Panin, S. V.; Kornienko, L. A.; Poltaranin, M. A.; Ivanova, L. R.; Suan, T. Nguen

    2014-11-14

    In order to compare effectiveness of adding solid lubricating fillers for polymeric composites based on ultra-high molecular weight polyethylene (UHMWPE) with graphite, molybdenum disulfide and polytetrafluoroethylene, their tribotechnical characteristics under dry friction, boundary lubrication and abrasive wearing were investigated. The optimal weight fractions of fillers in terms of improving wear resistance have been determined. The supramolecular structure and topography of wear track surfaces of UHMWPE-based composites with different content of fillers have been studied.

  17. QSAR and molecular docking studies on oxindole derivatives as VEGFR-2 tyrosine kinase inhibitors.

    PubMed

    Kang, Cong-Min; Liu, Dong-Qing; Zhao, Xu-Hao; Dai, Ying-Jie; Cheng, Jia-Gao; Lv, Ying-Tao

    2016-01-01

    The three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for 30 oxindole derivatives as vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitors by using comparative molecular field analysis (CoMFA) and comparative similarity indices analysis comparative molecular similarity indices analysis (CoMSIA) techniques. With the CoMFA model, the cross-validated value (q(2)) was 0.777, the non-cross-validated value (R(2)) was 0.987, and the external cross-validated value ([Formula: see text]) was 0.72. And with the CoMSIA model, the corresponding q(2), R(2) and [Formula: see text] values were 0.710, 0.988 and 0.78, respectively. Docking studies were employed to bind the inhibitors into the active site to determine the probable binding conformation. The binding mode obtained by molecular docking was in good agreement with the 3D-QSAR results. Based on the QSAR models and the docking binding mode, a set of new VEGFR-2 tyrosine kinase inhibitors were designed, which showed excellent predicting inhibiting potencies. The result revealed that both QSAR models have good predictive capability to guide the design and structural modification of homologic compounds. It is also helpful for further research and development of new VEGFR-2 tyrosine kinase inhibitors.

  18. Formulation/cure technology for ultrahigh molecular weight silphenylene-siloxane polymers

    NASA Technical Reports Server (NTRS)

    Hundley, N. H.; Patterson, W. J.

    1985-01-01

    Molecular weights above one million were achieved for methylvinylsilphenylene-siloxane terpolymers using a two-stage polymerization technique which was successfully scaled up to 200 grams. The resulting polymer was vulcanized by two different formulations and compared to an identically formulated commercial methylvinyl silicone on the basis of ultimate strength, Young's modulus, percent elongation at failure, and tear strength. Relative thermal/oxidative stabilities of the elastomers were assessed by gradient and isothermal thermogravimetric analyses performed in both air and nitrogen. The experimental elastomer exhibited enhanced thermal/oxidative stability and possed equivalent or superior mechanical properties. The effect of variations in prepolymer molecular weight on mechanical properties was also investigated.

  19. Preparation and Characterization of Low Molecular Weight Heparin by Liquid Phase Plasma Method.

    PubMed

    Lee, Do-Jin; Kim, Hangun; Kim, Byung Hoon; Park, Young-Kwon; Lee, Heon; Park, Sung Hoon; Jung, Sang-Chul

    2015-08-01

    An liquid phase plasma process system was applied to the production of low molecular weight heparin. The molecular weight of produed heparin decreased with increasing liquid phase plasma treatment time. The abscission of the chemical bonds between the constituents of heparin by liquid phase plasma reaction did not alter the characteristics of heparin. Formation of any by-products due to side reaction was not observed. It is suggested that heparin was depolymerized by active oxygen radicals produced during the liquid phase plasma reaction.

  20. Extraction of berkelium (IV) by neutral organophosphorus compounds and high molecular weight amines

    SciTech Connect

    Myasoedov, B.F.; Milyukova, M.S.; Malikov, D.A.

    1984-01-01

    The extraction behaviour of berkelium (IV) from inorganic acid solutions using neutral organophosphorus compounds and high molecular weight amines was studied. Distribution coefficients as a function of the nature and concentration of acid, extractant, organic solvent and oxidant were examined. The stoichiometry of Bk(IV) extraction has been studied and the composition of the extracted species has been determined. The data obtained allowed the authors to work out the extraction methods of separation and purification of berkelium from transplutonium elements, rare earths and several fission products using neutral organophosphorus compounds and high molecular weight amines. 8 figures, 2 tables.

  1. Low molecular weight thermostable {beta}-D-glucosidase from Acidothermus cellulolyticus

    DOEpatents

    Himmel, M.E.; Tucker, M.P.; Adney, W.S.; Nieves, R.A.

    1995-07-11

    A purified low molecular weight {beta}-D-glucosidase is produced from Acidothermus cellulolyticus ATCC 43068. The enzyme is water soluble, possesses activity against pNP-{beta}-D-glucopyranoside, has a high of degree of stability toward heat, exhibits optimal temperature activity at about 65 C at a pH range of from about 2 to about 7, has an inactivation temperature of about 80 C at a pH range of from about 2 to about 7 and has a molecular weight of about 50.5--54.5 kD as determined by SDS-PAGE. 6 figs.

  2. Apoptosis-inducing activity of high molecular weight fractions of tea extracts.

    PubMed

    Hayakawa, S; Kimura, T; Saeki, K; Koyama, Y; Aoyagi, Y; Noro, T; Nakamura, Y; Isemura, M

    2001-02-01

    High molecular weight fractions of green tea, black tea, oolong tea, and pu-erh tea were found to induce apoptosis in human monoblastic leukemia U937 cells by examination of their ability to inhibit cell proliferation and to induce apoptotic body formation and DNA ladder formation. These tea fractions were also shown to induce apoptosis in stomach cancer MKN-45 cells. In addition to known antitumor-promoting activity of tea high molecular weight fractions, their apoptosis-inducing activity may contribute to cancer chemopreventive effects of tea.

  3. Low molecular weight thermostable .beta.-D-glucosidase from acidothermus cellulolyticus

    DOEpatents

    Himmel, Michael E.; Tucker, Melvin P.; Adney, William S.; Nieves, Rafael A.

    1995-01-01

    A purified low molecular weight .beta.-D-glucosidase is produced from Acidothermus cellulolyticus ATCC 43068. The enzyme is water soluble, possesses activity against pNP-.beta.-D-glucopyranoside, has a high of degree of stability toward heat, exhibits optimal temperature activity at about 65.degree. C. at a pH range of from about 2 to about 7, has an inactivation temperature of about 80.degree. C. at a pH range of from about 2 to about 7 and has a molecular weight of about 50.5-54.5 kD as determineded by SDS-PAGE.

  4. Synthesis, biological characterization and molecular modeling insights of spirochromanes as potent HDAC inhibitors.

    PubMed

    Thaler, Florian; Moretti, Loris; Amici, Raffaella; Abate, Agnese; Colombo, Andrea; Carenzi, Giacomo; Fulco, Maria Carmela; Boggio, Roberto; Dondio, Giulio; Gagliardi, Stefania; Minucci, Saverio; Sartori, Luca; Varasi, Mario; Mercurio, Ciro

    2016-01-27

    In the last decades, inhibitors of histone deacetylases (HDAC) have become an important class of anti-cancer agents. In a previous study we described the synthesis of spiro[chromane-2,4'-piperidine]hydroxamic acid derivatives able to inhibit histone deacetylase enzymes. Herein, we present our exploration for new derivatives by replacing the piperidine moiety with various cycloamines. The goal was to obtain highly potent compounds with a good in vitro ADME profile. In addition, molecular modeling studies unravelled the binding mode of these inhibitors.

  5. The Vertex Version of Weighted Wiener Number for Bicyclic Molecular Structures

    PubMed Central

    Gao, Wei; Wang, Weifan

    2015-01-01

    Graphs are used to model chemical compounds and drugs. In the graphs, each vertex represents an atom of molecule and edges between the corresponding vertices are used to represent covalent bounds between atoms. We call such a graph, which is derived from a chemical compound, a molecular graph. Evidence shows that the vertex-weighted Wiener number, which is defined over this molecular graph, is strongly correlated to both the melting point and boiling point of the compounds. In this paper, we report the extremal vertex-weighted Wiener number of bicyclic molecular graph in terms of molecular structural analysis and graph transformations. The promising prospects of the application for the chemical and pharmacy engineering are illustrated by theoretical results achieved in this paper. PMID:26640513

  6. Synthesis of the low molecular weight heat shock proteins in plants

    SciTech Connect

    Mansfield, M.A.; Key, J.L. )

    1987-08-01

    Heat shock of living tissue induces the synthesis of a unique group of proteins, the heat shock proteins. In plants, the major group of heat shock proteins has a molecular mass of 15 to 25 kilodaltons. Accumulation to these proteins to stainable levels has been reported in only a few species. To examine accumulation of the low molecular weight heat shock proteins in a broader range of species, two-dimensional electrophoresis was used to resolve total protein from the following species: soybean (Glycine max L. Merr., var Wayne), pea (Pisum sativum L., var Early Alaska), sunflower (Helianthus annuus L.), wheat (Triticum asetivum L.), rice (Oryza sativa L., cv IR-36), maize (Zea mays L.), pearl millet (Pennisetum americanum L. Leeke, line 23DB), and Panicum miliaceum L. When identified by both silver staining and incorporation of radiolabel, a diverse array of low molecular weight heat shock proteins was synthesized in each of these species. These proteins accumulated to significant levels after three hours of heat shock but exhibited considerable heterogeneity in isoelectric point, molecular weight, stainability, and radiolabel incorporation. Although most appeared to be synthesized only during heat shock, some were detectable at low levels in control tissue. Compared to the monocots, a higher proportion of low molecular weight heat shock proteins was detectable in control tissues from dicots.

  7. Effect of molecular weight on the electrophoretic deposition of carbon black nanoparticles in moderately viscous systems.

    PubMed

    Modi, Satyam; Panwar, Artee; Mead, Joey L; Barry, Carol M F

    2013-08-06

    Electrophoretic deposition from viscous media has the potential to produce in-mold assembly of nanoparticles onto three-dimensional parts in high-rate, polymer melt-based processes like injection molding. The effects of the media's molecular weight on deposition behavior were investigated using a model system of carbon black and polystyrene in tetrahydrofuran. Increases in molecular weight reduced the electrophoretic deposition of the carbon black particles due to increases in suspension viscosity and preferential adsorption of the longer polystyrene chains on the carbon black particles. At low deposition times (≤5 s), only carbon black deposited onto the electrodes, but the deposition decreased with increasing molecular weight and the resultant increases in suspension viscosity. For longer deposition times, polystyrene codeposited with the carbon black, with the amount of polystyrene increasing with molecular weight and decreasing with greater charge on the polystyrene molecules. This deposition behavior suggests that use of lower molecular polymers and control of electrical properties will permit electrophoretic deposition of nanoparticles from polymer melts for high-rate, one-step fabrication of nano-optical devices, biochemical sensors, and nanoelectronics.

  8. Chemical characterization of high molecular weight dissolved organic matter in fresh and marine waters

    NASA Astrophysics Data System (ADS)

    Repeta, Daniel J.; Quan, Tracy M.; Aluwihare, Lihini I.; Accardi, AmyMarie

    2002-03-01

    The high molecular weight fraction of dissolved organic matter in a suite of lakes, rivers, seawater, and marine sediment interstitial water samples was collected by ultrafiltration and characterized by molecular level and spectroscopic techniques. Proton nuclear magnetic resonance spectra of all samples show a high degree of similarity, with major contributions from carbohydrates, bound acetate, and lipids. Molecular level analyses of neutral sugars show seven monosaccharides, rhamnose, fucose, arabinose, xylose, mannose, glucose, and galactose, to be abundant, and to occur in comparable relative amounts in each sample. Previous studies have emphasized the distinctive composition of dissolved humic substances in fresh and marine waters, and have attributed these differences to sources and transformations of organic matter unique to each environment. In contrast we find a large fraction of freshwater high molecular weight dissolved organic matter (HMWDOM; > 1kD) to be indistinguishable from marine HMWDOM in bulk and molecular-level chemical properties. Aquatic HMWDOM is similar in chemical composition to biologically derived acylated heteropolysaccharides isolated from marine algal cultures, suggesting a biological source for some fraction of persistent HMWDOM. High molecular weight DOC contributes 51 ± 26% of the total DOC, and monosaccharides 18 ± 8% of the total HMWDOC in our freshwater samples. These contributions are on average higher and more variable, but not significantly different than for surface seawater (30% and 16% respectively). Biogeochemical processes that produce, accumulate, and recycle DOM may therefore share important similarities and be broadly comparable across a range of environmental settings.

  9. The Combined Influence of Molecular Weight and Temperature on the Aging and Viscoelastic Response of a Glassy Thermoplastic Polyimide

    NASA Technical Reports Server (NTRS)

    Nicholson, Lee M.; Whitley, Karen S.; Gates, Thomas S.

    2000-01-01

    The effect of molecular weight on the viscoelastic performance of an advanced polymer (LaRC-SI) was investigated through the use of creep compliance tests. Testing consisted of short-term isothermal creep and recovery with the creep segments performed under constant load. The tests were conducted at three temperatures below the glass transition temperature of five materials of different molecular weight. Through the use of time-aging-time superposition procedures, the material constants, material master curves and aging-related parameters were evaluated at each temperature for a given molecular weight. The time-temperature superposition technique helped to describe the effect of temperature on the timescale of the viscoelastic response of each molecular weight. It was shown that the low molecular weight materials have higher creep compliance and creep rate, and are more sensitive to temperature than the high molecular weight materials. Furthermore, a critical molecular weight transition was observed to occur at a weight-average molecular weight of M (bar) (sub w) 25000 g/mol below which, the temperature sensitivity of the time-temperature superposition shift factor increases rapidly. The short-term creep compliance data were used in association with Struik's effective time theory to predict the long-term creep compliance behavior for the different molecular weights. At long timescales, physical aging serves to significantly decrease the creep compliance and creep rate of all the materials tested.

  10. Different cleavage site for high molecular weight kininogen in vivo following intravenous injection of dextran sulfate in the rabbit

    SciTech Connect

    Wiggins, R.C.

    1986-04-01

    Purified radiolabeled rabbit Hageman factor, prekallikrein, and high molecular weight kininogen were used to examine Hageman factor system molecular dynamics after the intravenous injection of heparin-like dextran sulfate polymer in the rabbit. Hageman factor system proteins rapidly disappeared from the circulation following dextran sulfate injection, as measured by radial immunodiffusion, by kaolin-releasable kinin formation, and by measuring circulating levels of radiolabeled Hageman factor, prekallikrein, and high molecular weight kininogen. /sup 125/I-Hageman factor was distributed mainly to lung, liver, and spleen following dextran sulfate injection. Proteolysis of circulating /sup 125/I-Hageman factor occurred at a site within a disulfide loop into fragments of 50,000 and 30,000 molecular weight. Proteolysis of /sup 125/I-prekallikrein also occurred with visualization of a 50,000 molecular weight fragment. Although extensive proteolysis of /sup 131/I-high molecular weight kininogen was observed, the cleavage fragments were not the same as those generated during contact activation in vitro. The major fragment of high molecular weight kininogen observed in vivo was at 80,000 molecular weight, in contrast to the 65,000 molecular weight fragment generated by kallikrein in vitro. These results indicate that high molecular weight kininogen can undergo proteolysis in vivo into fragments not known to be associated with kinin release.

  11. Polyaspartate scale inhibitors -- Biodegradable alternatives to polyacrylates

    SciTech Connect

    Ross, R.J.; Low, K.C.; Shannon, J.E.

    1996-12-01

    Polyaspartates are highly biodegradable alternatives to polyacrylate based scale inhibitors. This paper presents laboratory testing data on polyaspartate inhibitors of calcium and barium mineral scales. The optimum molecular weight for polyaspartate inhibitors of calcium carbonate, calcium sulfate and barium sulfate mineral scales was determined to be between 1,000 and 4,000 Mw (weight average molecular weight as calculated by Size Exclusion Chromatography). For inhibition of calcium carbonate and barium sulfate, polyaspartates in the range of 3,000-4,000 Mw were most effective. For calcium sulfate inhibition, the optimum molecular weight lies in the 1,000 to 2,000 Mw range. Biodegradability data (OECD 301B Ready Biodegradability) on polyaspartates of a variety of molecular weights is also presented which demonstrates the high biodegradability of this class of mineral scale inhibitors.

  12. Spontaneous assembly of HSP90 inhibitors at water/octanol interface: A molecular dynamics simulation study

    NASA Astrophysics Data System (ADS)

    Zolghadr, Amin Reza; Boroomand, Samaneh

    2017-02-01

    Drug absorption at an acceptable dose depends on the pair of solubility and permeability. There are many potent therapeutics that are not active in vivo, presumably due to the lack of capability to cross the cell membrane. Molecular dynamics simulation of radicicol, diol-radicicol, cyclopropane-radicicol and 17-DMAG were performed at water/octanol interface to suggest interfacial activity as a physico-chemical characteristic of these heat shock protein 90 (HSP90) inhibitors. We have observed that orally active HSP90 inhibitors form aggregates at the water/octanol and DPPC-lipid/water interfaces by starting from an initial configuration with HSP90 inhibitors embedded in the water matrix.

  13. Reorganization of low-molecular-weight fraction of plasma proteins in the annual cycle of cyprinidae.

    PubMed

    Andreeva, A M; Lamas, N E; Serebryakova, M V; Ryabtseva, I P; Bolshakov, V V

    2015-02-01

    Reorganization of the low-molecular-weight fraction of cyprinid plasma was analyzed using various electrophoretic techniques (disc electrophoresis, electrophoresis in polyacrylamide concentration gradient, in polyacrylamide with urea, and in SDS-polyacrylamide). The study revealed coordinated changes in the low-molecular-weight protein fractions with seasonal dynamics and related reproductive rhythms of fishes. We used cultured species of the Cyprinidae family with sequenced genomes for the detection of these interrelations in fresh-water and anadromous cyprinid species. The common features of organization of fish low-molecular-weight plasma protein fractions made it possible to make reliable identification of their proteins. MALDI mass-spectrometry analysis revealed the presence of the same proteins (hemopexin, apolipoproteins, and serpins) in the low-molecular-weight plasma fraction in wild species and cultured species with sequenced genomes (carp, zebrafish). It is found that the proteins of the first two classes are organized as complexes made of protein oligomers. Stoichiometry of these complexes changes in concordance with the seasonal and reproductive rhythms.

  14. TOXICOLOGICAL HIGHLIGHT (REDOX REDUX: A CLOSER LOOK AT CONCEPTAL LOW MOLECULAR WEIGHT THIOLS)

    EPA Science Inventory

    Glutathione (GSH) is present as the most abundant low molecular weight thiol (LMWT) in virtually all mitochondria-bearing eucaryotic cells, often at millimolar concentrations (Meister, 1988). Functions of GSH include roles in DNA and protein synthesis, maintenance of cell membra...

  15. Holographic recording medium employing a photoconductive layer and a low molecular weight microcrystalline polymeric layer

    NASA Technical Reports Server (NTRS)

    Gange, Robert Allen (Inventor)

    1977-01-01

    A holographic recording medium comprising a conductive substrate, a photoconductive layer and an electrically alterable layer of a linear, low molecular weight hydrocarbon polymer has improved fatigue resistance. An acrylic barrier layer can be interposed between the photoconductive and electrically alterable layers.

  16. Molecular Weight Dependence of Interdiffusion and Adhesion of Polymers at Short Contact Times.

    PubMed

    Gurney, Robert; Henry, Anastase; Schach, Regis; Lindner, Anke; Creton, Costantino

    2017-02-21

    The autohesion and subsequent debonding of thin layers of three linear and monodisperse random copolymers of styrene-butadiene (SBR) with molecular weights varying between 30 and 75 times the average molecular weight between entanglements Me were investigated using a carefully controlled tack adhesion testing device in conjunction with a fast camera setup over a range of contact times tc (10 ms to 10 s) much shorter in comparison to the terminal relaxation times of the polymers. The evolution of the stress-strain curves and debonding mechanisms with increasing contact time was examined, and the work required to debond the layers was found to be strongly dependent on molecular weight at long contact times, but not at short contact times. We propose a cutoff contact time of 300 ms, corresponding to 10(4) times the entanglement time τe after which molecular weight becomes important in controlling the interdiffusion process and the debonding mechanisms of the tack test. For contact times over 300 ms, the debonding energy plotted as a function of tc normalized by the reptation time τrep, collapses onto a master curve. Below this threshold tc, by comparing the adhesion of SBR on itself with the adhesion of SBR on glass, we also show that interdiffusion plays a part in adhesion of two identical polymer layers even at the shortest contact times, where the interdiffusion is controlled by the number of entanglements formed which scales with 1/√N.

  17. Oligomeric cationic polymethacrylates: a comparison of methods for determining molecular weight.

    PubMed

    Locock, Katherine E S; Meagher, Laurence; Haeussler, Matthias

    2014-02-18

    This study compares three common laboratory methods, size-exclusion chromatography (SEC), (1)H nuclear magnetic resonance (NMR), and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), to determine the molecular weight of oligomeric cationic copolymers. The potential bias for each method was examined across a series of polymers that varied in molecular weight and cationic character (both choice of cation (amine versus guanidine) and relative proportion present). SEC was found to be the least accurate, overestimating Mn by an average of 140%, owing to the lack of appropriate cationic standards available, and the complexity involved in estimating the hydrodynamic volume of copolymers. MALDI-TOF approximated Mn well for the highly monodisperse (Đ < 1.1), low molecular weight (degree of polymerization (DP) <50) species but appeared unsuitable for the largest polymers in the series due to the mass bias associated with the technique. (1)H NMR was found to most accurately estimate Mn in this study, differing to theoretical values by only 5.2%. (1)H NMR end-group analysis is therefore an inexpensive and facile, primary quantitative method to estimate the molecular weight of oliogomeric cationic polymethacrylates if suitably distinct end-groups signals are present in the spectrum.

  18. Effect of high molecular weight glutenin subunit allelic composition on wheat flour tortilla quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wheat cultivars possessing quality attributes needed to produce optimum quality tortillas have not been identified. This study investigated the effect of variations in high molecular weight glutenin subunits encoded at the Glu-1 loci (Glu-A1, Glu-B1, Glu-D1) on dough properties and tortilla quality....

  19. Incorporation of high-molecular-weight glutenin subunits into doughs using 2 gram mixograph and extensigraphs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To study the contributions of high-molecular-weight glutenin subunits (HMW-GS) to the gluten macropolymer and dough properties, wheat HMW-GS (x- and y-types) are synthesized in a bacterial expression system. These subunits are then purified and used to supplement dough mixing and extensigraph exper...

  20. Properties of UV-Cured Polyurethane Acrylates: Effect of Polyol Type and Molecular Weight

    DTIC Science & Technology

    1984-06-20

    glass transition temperature versus polypropylene oxide molecular weight for the IEM-PP series materials. Figure 5. DSC thermograms of the IEM-ES-25N...before and after one minute of UV-curing. Figure 3. DSC thermograms of the IEM-PP-O series materials before C---) and after (-) UV-curing. Figure 4. DSC

  1. Polyacrylamide Molecular Weight and Phosphogypsum Effects on Infiltration and Erosion in Semi-Arid Soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seal formation at the surface of semi-arid soils during rainstorms reduces soil infiltration rate (IR) and causes runoff and erosion. Surface application of dry anionic polyacrylamide (PAM) with high molecular weight (MW) has been found to be effective in stabilizing soil aggregates, and decreasing ...

  2. Polyacrylamide molecular weight and phosphogypsum effects on infiltration and erosion in semi-arid soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seal formation at the surface of semi-arid soils during rainstorms reduces soil infiltration rate (IR) and causes runoff and erosion. Surface application of dry anionic polyacrylamide (PAM) with high molecular weight (MW) has been found to be effective in stabilizing soil aggregates, and decreasing ...

  3. Infiltration and Erosion in Soils Treated with Dry PAM of Two Molecular Weights and Phosphogypsum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil surface application of dissolved linear polyacrylamide (PAM) of high molecular weight (MW) can mitigate seal formation, runoff and erosion, especially when added with a source of electrolytes (e.g., gypsum). Practical difficulties associated with PAM solution application prohibited commercial u...

  4. Extraction of low molecular weight polynuclear aromatic hydrocarbons from ashes of coal-operated power plants

    SciTech Connect

    Mangani, F.; Cappiello, A.; Crescentini, G.; Bruner, F.; Bonfanti, L.

    1987-09-01

    A new procedure based on liquid-solid chromatography for the extraction of polynuclear aromatic hydrocarbons has been implemented. This yields results analogous to those of Soxhlet extraction for low molecular weight compounds. A very important reduction in the time required for sample preparation prior to gas chromatography/mass spectrometry analysis is obtained.

  5. Effects of molecular weight on the diffusion coefficient of aquatic dissolved organic matter and humic substances.

    PubMed

    Balch, J; Guéguen, C

    2015-01-01

    In situ measurements of labile metal species using diffusive gradients in thin films (DGT) passive samplers are based on the diffusion rates of individual species. Although most studies have dealt with chemically isolated humic substances, the diffusion of dissolved organic matter (DOM) across the hydrogel is not well understood. In this study, the diffusion coefficient (D) and molecular weight (MW) of 11 aquatic DOM and 4 humic substances (HS) were determined. Natural, unaltered aquatic DOM was capable of diffusing across the diffusive gel membrane with D values ranging from 2.48×10(-6) to 5.31×10(-6) cm(2) s(-1). Humic substances had diffusion coefficient values ranging from 3.48×10(-6) to 6.05×10(-6) cm(2) s(-1), congruent with previous studies. Molecular weight of aquatic DOM and HS samples (∼500-1750 Da) measured using asymmetrical flow field-flow fractionation (AF4) strongly influenced D, with larger molecular weight DOM having lower D values. No noticeable changes in DOM size properties were observed during the diffusion process, suggesting that DOM remains intact following diffusion across the diffusive gel. The influence of molecular weight on DOM mobility will assist in further understanding and development of the DGT technique and the uptake and mobility of contaminants associated with DOM in aquatic environments.

  6. Sedimentation Coefficient, Frictional Coefficient, and Molecular Weight: A Preparative Ultracentrifuge Experiment for the Advanced Undergraduate Laboratory.

    ERIC Educational Resources Information Center

    Halsall, H. B.; Wermeling, J. R.

    1982-01-01

    Describes an experiment using a high-speed preparative centrifuge and calculator to demonstrate effects of the frictional coefficient of a macromolecule on its rate of transport in a force field and to estimate molecular weight of the macromolecule using an empirical relationship. Background information, procedures, and discussion of results are…

  7. A global survey of low-molecular weight carbohydrates in lentils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lentils contain a range of low-molecular weight carbohydrates (LMWC); however, they have not been well characterized. The objectives of this study were to (1) determine the concentrations of LMWC in lentils grown in different environments and (2) identify any genetic and environmental effects on tho...

  8. Recovering ultraclean lignins of controlled molecular weight from Kraft black-liquor lignins.

    PubMed

    Klett, A S; Chappell, P V; Thies, M C

    2015-08-18

    By operating in a region of liquid-liquid equilibrium, hot acetic acid-water mixtures can be used to simultaneously clean, fractionate, and solvate Kraft black-liquor lignins. Lignin-rich liquid phases of controlled molecular weight with key metals contents reduced to <50 ppm are obtained without a washing step.

  9. Effect of mahlep on molecular weight distribution of cookie flour gluten proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Size Exclusion-High performance Chromatography (SE-HPLC) has been extensively used in molecular weight distribution analysis of wheat proteins. In this study the protein analysis was conducted on different cookie dough blends with different percentages of some ingredients. The mean chromatography ...

  10. Methanol-induced chain termination in poly(3-hydroxybutyrate) biopolymers: molecular weight control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A systematic study was performed to demonstrate the impact of methanol (MeOH) on poly(3-hydroxybutyrate) (PHB) synthesis and molecular weight (MW) control. Glycerine (init. conc. = 1.0%; w/v), was used as the primary carbon source in batch-culture fermentations with varying concentrations (0 to 0.85...

  11. Microfluidics Meets Dilute Solution Viscometry: An Undergraduate Laboratory to Determine Polymer Molecular Weight Using a Microviscometer

    ERIC Educational Resources Information Center

    Pety, Stephen J.; Lu, Hang; Thio, Yonathan S.

    2011-01-01

    This paper describes a student laboratory experiment to determine the molecular weight of a polymer sample by measuring the viscosity of dilute polymer solutions in a PDMS microfluidic viscometer. Sample data are given for aqueous solutions of poly(ethylene oxide) (PEO). A demonstration of shear thinning behavior using the microviscometer is…

  12. A global survey of low-molecular weight carbohydrates in lentils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lentils contain a range of low-molecular weight carbohydrates (LMWC); however, those have not been well characterized. The objectives of this study were to (1) determine the concentrations of LMWC in lentils grown in six locations, and (2) identify any genetic and environmental effects on those LMWC...

  13. Determination of low molecular weight thiols using monobromobimane fluorescent labeling and high-performance liquid chromatography

    NASA Technical Reports Server (NTRS)

    Fahey, Robert C.; Newton, Gerald L.

    1988-01-01

    Methods are described for the preparation and high-performance liquid chromatography (HPLC) analysis of monobromobimane derivatives of low molecular weight thiols in extracts of biological samples. Typical problems encountered in the development and application of these methods are discussed. Analysis of mung bean extract is used as an example.

  14. Comparison of mass spectrometric techniques for generating molecular weight information on a class of ethoxylated oligomers.

    PubMed

    Parees, D M; Hanton, S D; Clark, P A; Willcox, D A

    1998-04-01

    The results of fast atom bombardment (FAB), time-of-flight secondary ion mass spectrometry (ToF-SIMS), matrix-assisted laser desorption/ionization (MALD/I), electrospray ionization (ESI), and field desorption (FD) analyses of ethoxylated oligomers of 2,4,7,9-tetramethyl-5-decyne-4,7-diol (Surfynol(®) 104) were compared.Each of these desorption mass spectrometry (MS) techniques can produce spectra of unfragmented cationized oligomers. From the observed ion series we calculate average molecular weight information. We have compared the results of mass spectrometric analyses of a series of ethoxylated Surfynol surfactants. Our data indicate that FAB, ToF-SIMS, MALDI/I, and ESI produce similar results for the lower molecular weight species, but that as the average molecular weight increases FAB and SIMS produce slightly lower results than MALD/I and FD. This could be due to increased fragmentation. ESI produced a result similar to FAB and SIMS for the highest average molecular weight material. Further experiments compare the mass spectral results with gas chromatographic quantitative data. Although gas chromatography is not expected to accurately analyze the higher mass oligomers, we observe significant differences in intensities of the short-chain oligomers (especially the 0- and 1-mers) when compared to the desorption mass spectrometer results. These differences may reflect poor cationization efficiency for very short oligomer chains in the mass spectrometric analyses.

  15. Exploratory data analysis of the dependencies between skin permeability, molecular weight and log P.

    PubMed

    Kilian, D; Lemmer, H J R; Gerber, M; du Preez, J L; du Plessis, J

    2016-06-01

    Molecular weight and log P remain the most frequently used physicochemical properties in models that predict skin permeability. However, several reports over the past two decades have suggested that predictions made by these models may not be sufficiently accurate. In this study, exploratory data analysis of the probabilistic dependencies between molecular weight, log P and log Kp was performed on a dataset constructed from the combination of several popular datasets. The results suggest that, in general, molecular weight and log P are poorly correlated to log Kp. However, after employing several exploratory data analysis techniques, regions within the dataset of statistically significant dependence were identified. As an example of the applicability of the information extracted from the exploratory data analyses, a multiple linear regression model was constructed, bounded by the ranges of dependence. This model gave reasonable approximations to log Kp values obtained from skin permeability studies of selected non-steroidal ant-inflammatory drugs (NSAIDs) administered from a buffer solution and a lipid-based drug delivery system. A method of testing whether a given drug falls within the regions of statistical dependence was also presented. Knowing the ranges within which molecular weight and log P are statistically related to log Kp can supplement existing methods of screening, risk analysis or early drug development decision making to add confidence to predictions made regarding skin permeability.

  16. Molecular weight distribution and functional group profiles of TEMPO-oxidized lyocell fibers.

    PubMed

    Milanovic, Jovana; Schiehser, Sonja; Milanovic, Predrag; Potthast, Antje; Kostic, Mirjana

    2013-10-15

    The effects of TEMPO-mediated oxidation, performed with NaClO, a catalytic amount of NaBr, and 2,2',6,6'-tetramethylpiperidine-1-oxy radical (TEMPO), were studied on lyocell fibers by means of GPC using multiple detection and group-selective fluorescence labeling according to the CCOA and FDAM methodology. The applied method determines functional group content as a sum parameter, as well as functional group profiles in relation to the molecular weight of the cellulose fibers. Both the CHO and COOH profiles, as well as molecular weight alterations, were analyzed. A significant decrease in the average molecular weight was obtained during the first hour of TEMPO-mediated oxidation, but prolonged oxidation time resulted in no strong additional chain scission. Significant amounts of COOH groups were introduced in the high molecular weight fractions by the oxidation with higher concentrations of NaClO (2.42-9.67 mmol NaClO/g fiber) after modification times of 1h or longer.

  17. Isoleucine epimerization and amino acid composition in molecular-weight separations of Pleistocene Genyornis eggshell

    NASA Astrophysics Data System (ADS)

    Kaufman, Darrell S.; Miller, Gifford H.

    1995-07-01

    This study explores the geochronological utility and analytical reproducibility of separating the high-molecular-weight fraction (HMW) from eggshells of the extinct late Pleistocene ratite, Genyornis, using disposable, prepacked gel-filtration columns. The superior integrity of ratite eggshell for the retention of amino acids indicates that this biomineral is better suited for this type of investigation than previously studied molluscan shell. To evaluate the reproducibility of the gel-filtration technique, we analyzed triplicate subsamples of three eggshells of different ages. The reproducibility, based on the average intrashell variation (coefficient of variation; CV) in the extent of isoleucine epimerization (aIle/Ile) in the HMW (enriched in molecules ca. >10,000 MW) is 3%, well within the range appropriate for geochronological purposes. The average intrashell variation in the total amino acid concentration (Σ[aa]) of the HMW is 5%, somewhat better than for the total acid hydrolysate (TOTAL) of the same samples (7%). To evaluate the relation between molecular weight and the rate of isoleucine epimerization, three molecular-weight fractions were separated using gel filtration, plus the naturally hydrolyzed free fraction (FREE), for each of four fossil eggshells. AIle/Ile increases with decreasing molecular weight in all shells, with a ca. sixfold to ninefold difference in ratios between the HMW andFREE, and a ca. fivefold difference between the HMW andTOTAL. Although linear correlations between aIle/Ile measured in each molecular-weight fraction and in theTOTAL are all highly significant (r ⩾ 0.951), the relation between the extent of epimerization in the HMW and in the TOTAL is best expressed as an exponential function (r = 0.951). This relation is consistent with the idea that, as the epimerization reaction approaches equilibrium in theTOTAL (ca. aIle/Ile > 1.1), its rate decreases beyond that of the HMW. The amino acid composition (relative percent of

  18. Selective Monocationic Inhibitors of Neuronal Nitric Oxide Synthase. Binding Mode Insights from Molecular Dynamics Simulations

    PubMed Central

    Huang, He; Ji, Haitao; Li, Huiying; Jing, Qing; Labby, Kristin Jansen; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

    2012-01-01

    The reduction of pathophysiologic levels of nitric oxide through inhibition of neuronal nitric oxide synthase (nNOS) has the potential to be therapeutically beneficial in various neurodegenerative diseases. We have developed a series of pyrrolidine-based nNOS inhibitors that exhibit excellent potencies and isoform selectivities (J. Am. Chem. Soc. 2010, 132, 5437). However, there are still important challenges, such as how to decrease the multiple positive charges derived from basic amino groups, which contribute to poor bioavailability, without losing potency and/or selectivity. Here we present an interdisciplinary study combining molecular docking, crystallography, molecular dynamics simulations, synthesis, and enzymology to explore potential pharmacophoric features of nNOS inhibitors and to design potent and selective monocationic nNOS inhibitors. The simulation results indicate that different hydrogen bond patterns, electrostatic interactions, hydrophobic interactions, and a water molecule bridge are key factors for stabilizing ligands and controlling ligand orientation. We find that a heteroatom in the aromatic head or linker chain of the ligand provides additional stability and blocks the substrate binding pocket. Finally, the computational insights are experimentally validated with double-headed pyridine analogs. The compounds reported here are among the most potent and selective monocationic pyrrolidine-based nNOS inhibitors reported to date, and 10 shows improved membrane permeability. PMID:22731813

  19. Molecular Shape Analysis-Guided Virtual Screening Platform for Adenosine Kinase Inhibitors

    PubMed Central

    Bhutoria, Savita; Das, Ballari; Ghoshal, Nanda

    2016-01-01

    We propose a new application of molecular shape descriptors in hierarchical selection during virtual screening (VS). Here, a structure-based pharmacophore and docking-guided VS protocol have been evolved to identify inhibitors against adenosine kinase (AK). The knowledge gained on the shape requirements has been extrapolated in classifying active and inactive molecules against this target. This classification enabled us to pick the appropriate ligand conformation in the binding site. We have suggested a set of hierarchical filters for VS, from a simple molecular shape analysis (MSA) descriptor-based recursive models to docking scores. This approach permits a systematic study to understand the importance of spatial requirements and limitations for inhibitors against AK. Finally, the guidelines on how to select compounds for AK to achieve success have been highlighted. The utility of this approach has been suggested by giving an example of database screening for plausible active compounds. PMID:27478367

  20. Resveratrol Co-Treatment Attenuates the Effects of HIV Protease Inhibitors on Rat Body Weight and Enhances Cardiac Mitochondrial Respiration

    PubMed Central

    Symington, Burger; Mapanga, Rudo F.; Norton, Gavin R.

    2017-01-01

    Since the early 1990s human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) emerged as a global health pandemic, with sub-Saharan Africa the hardest hit. While the successful roll-out of antiretroviral (ARV) therapy provided significant relief to HIV-positive individuals, such treatment can also elicit damaging side-effects. Here especially HIV protease inhibitors (PIs) are implicated in the onset of cardio-metabolic complications such as type-2 diabetes and coronary heart disease. As there is a paucity of data regarding suitable co-treatments within this context, this preclinical study investigated whether resveratrol (RSV), aspirin (ASP) or vitamin C (VitC) co-treatment is able to blunt side-effects in a rat model of chronic PI exposure (Lopinavir/Ritonavir treatment for 4 months). Body weights and weight gain, blood metabolite levels (total cholesterol, HDL, LDL, triglycerides), echocardiography and cardiac mitochondrial respiration were assessed in PI-treated rats ± various co-treatments. Our data reveal that PI treatment significantly lowered body weight and cardiac respiratory function while no significant changes were found for heart function and blood metabolite levels. Moreover, all co-treatments ameliorated the PI-induced decrease in body weight after 4 months of PI treatment, while RSV co-treatment enhanced cardiac mitochondrial respiratory capacity in PI-treated rats. This pilot study therefore provides novel hypotheses regarding RSV co-treatment that should be further assessed in greater detail. PMID:28107484

  1. Depletion of high molecular weight dextran from the red cell surface measured by particle electrophoresis.

    PubMed

    Rad, Samar; Gao, Jie; Meiselman, Herbert J; Baskurt, Oguz K; Neu, Björn

    2009-02-01

    The reversible aggregation of human red blood cells (RBC) by proteins or polymers continues to be of biological and biophysical interest, yet the mechanistic details governing the process are still being explored. A depletion model has been proposed for aggregation by the neutral polyglucose dextran and its applicability at high molecular weights has been recently documented. In the present study the depletion of high molecular weight dextrans on the red cell surface was measured as a function of polymer molecular mass (40 kDa-28 MDa), ionic strength (5 and 15 mM NaCl) and polymer concentration (< or =0.9 g/dL). The experimental data clearly indicate an increasing depletion effect with increasing molecular weight: the effects of medium viscosity on RBC mobility were markedly overestimated by the Helmholtz-Smoluchowski relation, with the difference increasing with dextran molecular mass. These results agree with the concept of polymer depletion near the RBC surface and lend strong support to a "depletion model" mechanism for dextran-mediated RBC aggregation. Our findings provide important new insight into polymer-RBC interactions and suggest the usefulness of this model for fundamental studies of cell-cell affinity and for the development of new agents to stabilize or destabilize specific bio-fluids.

  2. Salicylate as a partial inhibitor of emotional fever and body weight set-point in rats: behavioral and neuroendocrine study.

    PubMed

    Michel, C; Frankham, P; Cabanac, M

    2003-03-01

    In this article, we report findings from behavioral and neuroendocrine experiments in rats under pharmacologically induced antipyretic conditions. Endpoints included emotional fever, body weight setpoint, and in situ corticotropin-releasing hormone mRNA (CRHmRNA) expression. Nine male Wistar rats were treated with acetylsalicylic acid (ASA) 0.04 g/kg ip in vehicle. On alternating days, all rats received saline (0.9% w/v) as a control. ASA was selected chiefly for its antipyretic and also for effects on metabolism. It has been demonstrated that gentle handling affects body weight and body temperature in rats. In Experiment 1, we investigated whether blocking emotional fever by ASA treatment would inhibit the lowering of the body weight setpoint induced by handling of the rats. Rats were exposed to a daily food-hoarding session under handling stress, and their body weight setpoints were calculated from the hoarding measurements. As rats received ASA and saline in an alternating manner, two setpoints were calculated. In Experiment 2, we performed neuroendocrine analyses of CRHmRNA expression in the same group of animals from Experiment 1. CRHmRNA was determined by in situ hybridization. Results indicated that ASA treatment in rats significantly decreased the body weight setpoint (P=.02) and significantly prevented increases in body temperature due to emotional fever (P=.03) when compared to their control values. Findings also revealed that hypothalamic CRH expression was increased when rats were treated with ASA. ASA did partially block fever induced by handling, but it is difficult to confirm whether emotion was also inhibited by treatment. Taken together, these results indicate that salicylates affect energy balance and might be a good inhibitor of body weight gain in rats.

  3. Design of new inhibitors for H5N1 avian influenza using a molecular dynamics simulation

    NASA Astrophysics Data System (ADS)

    Park, Jin Woo; Jo, Won Ho

    2008-03-01

    Recently, there has been a growing interest in the treatment of H5N1 avian influenza. One of the most widely used antiviral agents is oseltamivir. However, it has been reported that oseltamivir is not as effective against the neuraminidase subtype N1 as it is against subtypes N2 and N9. In our research we addressed this problem by designing new inhibitors and these altered inhibitor's binding affinities were calculated. In this study, we introduced chemical groups to the existing oseltamivir, so to fit into the newly discovered cavity in the subtype N1. When the binding strengths of the oseltamivir and the newly designed inhibitors for N1 were calculated to examine the drug efficiency through a molecular dynamics simulation, then compared with each other, it was found that one of the designed molecules exhibited a strong binding affinity, with more than twice the binding strength than that of oseltamivir. Since the aforementioned designed inhibitor appears to have the possibility for oral activity according to the criteria of human oral bioavailability, we propose that the inhibitor is a promising antiviral drug for H5N1 avian influenza.

  4. Self-assembled tetranuclear palladium catalysts that produce high molecular weight linear polyethylene.

    PubMed

    Shen, Zhongliang; Jordan, Richard F

    2010-01-13

    The phosphine-bis-arenesulfonate ligand PPh(2-SO(3)Li-4-Me-Ph)(2) (Li(2)[OPO]) coordinates as a kappa(2)-P,O chelator in Li[(Li-OPO)PdMe(Cl)] (2a) and (Li-OPO)PdMe(L) (L = pyridine (2b); MeOH (2d); 4-(5-nonyl)pyridine) (py', 3)). 2a reacts with AgPF(6) to form {(Li-OPO)PdMe}(n) (2c). Photolysis of 2d yields {(OPO)Pd}(2) (5) in which the [OPO](2-) ligand coordinates as a kappa(3)-O,P,O pincer. 3 self-assembles into a tetramer in which four (Li-OPO)PdMe(py') units are linked by Li-O bonds that form a central Li(4)S(4)O(12) cage. The Pd centers are equivalent but are spatially separated into two identical pairs. The Pd-Pd distance within each pair is 6.04 A. IR data (upsilon(ArSO(3)(-)) region) suggest that the solid state structures of 2a-c are similar to that of 3. 3 reacts with the cryptand Krypt211 to form [Li(Krypt211)][(OPO)PdMe(py')] (4). 3 is in equilibrium with a monomeric (Li-OPO)PdMe(py') species (3') in solution. 2a-c and 3 produce polyethylene (PE) with high molecular weight and a broad molecular weight distribution, characteristic of multisite catalysis. Under conditions where the tetrameric structure remains substantially intact, the PE contains a substantial high molecular weight fraction, while, under conditions where fragmentation is more extensive, the PE contains a large low molecular weight fraction. These results suggest that the tetrameric assembly gives rise to the high molecular weight polymer. In contrast, the monomeric complex 4, which contains a free pendant sulfonate group that can bind to Pd, oligomerizes ethylene to a Schultz-Flory distribution of C(4)-C(18) oligomers.

  5. Low-molecular-weight heparin prophylaxis: preoperative versus postoperative initiation in patients undergoing elective hip surgery.

    PubMed

    Hull, R D; Pineo, G F; MacIsaac, S

    2001-01-01

    Administration of low-molecular-weight heparin prophylaxis in elective hip implant patients commonly begins 12 h preoperatively in European practices to optimize effectiveness, and 12 to 24 h postoperatively in North American practices to optimize safety. A meta-analysis comparing these two treatment regimes revealed that preoperative initiation demonstrated greater efficacy and superior safety for patients (10.0% rate of total deep-vein thrombosis vs. 15.3%, P = .023). In addition to the pre/postsurgical debate, proximity of initiation of low-molecular-weight heparin in relation to surgery is an issue of critical importance. Recent studies revealed that beginning therapy immediately within 2 h preoperatively or 6 h postoperatively dramatically decreased the risk of venous thrombosis. An investigation of low-molecular-weight heparin prophylaxis initiated 2 h before elective hip surgery or approximately 6 h after surgery compared with warfarin sodium revealed that total and proximal deep-vein thrombosis rates were reduced in patients receiving low-molecular-weight heparin compared with warfarin. The frequencies of deep-vein thrombosis for patients receiving preoperative and postoperative dalteparin vs. warfarin for all deep-vein thrombosis were 36 of 337 (10.7%, P < .001) and 44 of 336 (13.1%, P < .001) vs. 81 of 338 (24.0%); and for proximal deep-vein thrombosis were 3 of 354 (0.8%, P = .035) and 3 of 358 (0.8%, P = .033) vs. 11 of 363 (3.0%). Relative risk reductions for the dalteparin groups vs. warfarin ranged from 45% to 72%. In this case, low-molecular-weight heparin administered in close proximity to surgery provided superior efficacy over warfarin. Major bleeding was significantly increased with the preoperative regimen but not the postoperative regimen.

  6. Intermolecular complexation of low-molecular-weight succinoglycans directs solubility enhancement of pindolol.

    PubMed

    Kim, Kyoungtea; Cho, Eunae; Choi, Jae Min; Kim, Hwanhee; Jang, Ahri; Choi, Youngjin; Lee, Im Soon; Yu, Jae-Hyuk; Jung, Seunho

    2014-06-15

    The low-molecular-weight succinoglycans isolated from Sinorhizobium meliloti are repeating octasaccharide units consisting of monomers, dimers, and trimers. Pindolol is a beta-blocker used to treat cardiovascular disorders. We investigated the formation of complexes between pindolol and low-molecular-weight succinoglycan monomers (SGs). Even though SGs have a linear structure, the solubility of pindolol in the presence of SGs was increased up to 7-fold compared with methyl-β-cyclodextrin reported as the best solubilizer of pindolol. Complexation of SGs with pindolol was confirmed by nuclear magnetic resonance, Fourier-transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy. Formation constants of complexes were determined from phase solubility diagrams. Conformation of complex was suggested based on a molecular docking study. The present study indicated that formation of pindolol/SGs complexes not only resulted in increased pindolol solubility but also could be useful for improving its clinical application as it did not affect cell viability.

  7. Structure–Activity Relationship Studies and Molecular Modeling of Naphthalene-Based Sphingosine Kinase 2 Inhibitors

    PubMed Central

    2016-01-01

    The two isoforms of sphingosine kinase (SphK1 and SphK2) are the only enzymes that phosphorylate sphingosine to sphingosine-1-phosphate (S1P), which is a pleiotropic lipid mediator involved in a broad range of cellular processes including migration, proliferation, and inflammation. SphKs are targets for various diseases such as cancer, fibrosis, and Alzheimer’s and sickle cell disease. Herein, we disclose the structure–activity profile of naphthalene-containing SphK inhibitors and molecular modeling studies that reveal a key molecular switch that controls SphK selectivity. PMID:26985306

  8. Identification of low-molecular-weight protein (SCP1) from shark cartilage with anti-angiogenesis activity and sequence similarity to parvalbumin.

    PubMed

    Rabbani-Chadegani, Azra; Abdossamadi, Sayeh; Bargahi, Afshar; Yousef-Masboogh, Marzeih

    2008-02-13

    Cartilage was considered as a possible natural source of anti-angiogenesis compounds due to its known avascular nature. In this study, a low-molecular-weight protein with an anti-angiogenesis activity was isolated from shark cartilage using a mild extraction procedure. The protein was purified to homogeneity by gel filtration and electroelution techniques and its N-terminal amino acid sequence was determined. The purified protein, designated as SCP1, represented a molecular weight of 13.7 kDa, pI of 6.9-7 and its N-terminal sequence revealed sequence similarity to alpha parvalbumin family. The protein inhibited angiogenesis when subjected to microvessel sprouting of collagen-embedded rat aortic ring assay. It is suggested that SCP1 could be considered as a new angiogenesis inhibitor derived from shark cartilage.

  9. Molecular characterization and biological response to respiration inhibitors of Pyricularia isolates from ctenanthe and rice plants.

    PubMed

    Paplomatas, Epaminondas J; Pappas, Athanasios C; Syranidou, Elene

    2005-07-01

    The molecular profile and the biological response of isolates of Pyricularia oryzae Cavara obtained from ctenanthe to two strobilurins (azoxystrobin, kresoxim-methyl) and the phenylpyridinamine fungicide fluazinam were characterized, and compared with isolates from rice plants. Five different isozymes (alpha-esterase, lactate, malate, isocitrate and sorbitol dehydrogenases) and five random decamer primers for RAPD-PCR were used to generate molecular markers. Using unweighted pair-group with arithmetic average analysis, ctenanthe isolates were found to form a separate group distinct from that of the rice isolates for both sets of markers. Amplified polymorphic sequences of mitochondrial cytochrome b that were digested with Fnu4HI or StyI revealed no differences among Pyricularia isolates at amino acid positions 143 or 129 which confer resistance to strobilurins in several fungi. In absence of the alternative respiration inhibitor salicylhydroxamic acid (SHAM) the three fungicides showed inferior and variable efficacy, with a trend toward the rice isolate being less sensitive. The addition of SHAM enhanced the effectiveness of all fungicides against isolates regardless of their origin. Appressorium formation was the most vulnerable target of action of the respiration inhibitors and azoxystrobin the most effective. This is the first report of a comparison between the molecular profiles and sensitivities to respiration inhibitors for Pyricularia oryzae isolates from a non-gramineous host and from rice.

  10. Memantine rescues transient cognitive impairment caused by high-molecular-weight aβ oligomers but not the persistent impairment induced by low-molecular-weight oligomers.

    PubMed

    Figueiredo, Cláudia P; Clarke, Julia R; Ledo, José Henrique; Ribeiro, Felipe C; Costa, Carine V; Melo, Helen M; Mota-Sales, Axa P; Saraiva, Leonardo M; Klein, William L; Sebollela, Adriano; De Felice, Fernanda G; Ferreira, Sergio T

    2013-06-05

    Brain accumulation of soluble amyloid-β oligomers (AβOs) has been implicated in synapse failure and cognitive impairment in Alzheimer's disease (AD). However, whether and how oligomers of different sizes induce synapse dysfunction is a matter of controversy. Here, we report that low-molecular-weight (LMW) and high-molecular-weight (HMW) Aβ oligomers differentially impact synapses and memory. A single intracerebroventricular injection of LMW AβOs (10 pmol) induced rapid and persistent cognitive impairment in mice. On the other hand, memory deficit induced by HMW AβOs (10 pmol) was found to be reversible. While memory impairment in LMW oligomer-injected mice was associated with decreased hippocampal synaptophysin and GluN2B immunoreactivities, synaptic pathology was not detected in the hippocampi of HMW oligomer-injected mice. On the other hand, HMW oligomers, but not LMW oligomers, induced oxidative stress in hippocampal neurons. Memantine rescued both neuronal oxidative stress and the transient memory impairment caused by HMW oligomers, but did not prevent the persistent cognitive deficit induced by LMW oligomers. Results establish that different Aβ oligomer assemblies act in an orchestrated manner, inducing different pathologies and leading to synapse dysfunction. Furthermore, results suggest a mechanistic explanation for the limited efficacy of memantine in preventing memory loss in AD.

  11. Flour Quality and Related Molecular Characterization of High Molecular Weight Glutenin Subunit Genes from Wild Emmer Wheat Accession TD-256.

    PubMed

    Zhang, Da-Le; He, Ting-Ting; Liang, Hui-Hui; Huang, Lu-Yu; Su, Ya-Zhong; Li, Yu-Ge; Li, Suo-Ping

    2016-06-22

    To clarify the effect of high molecular weight glutenin subunit (HMW-GS) from wild emmer wheat on flour quality, which has the same mobility as that from common wheat, the composition and molecular characterization of HMW-GS from wild emmer wheat accession TD-256, as well as its flour quality, were intensively analyzed. It is found that the mobilities of Glu-A1 and Glu-B1 subunits from TD-256 are consistent with those of bread wheat cv. 'XiaoYan 6'. Nevertheless, dough rheological properties of TD-256 reveal its poor flour quality. In the aspect of molecular structure from HMW-GS, only two conserved cysteine residues can be observed in the deduced protein sequence of 1Bx14* from TD-256, while most Glu-1Bx contain four conserved cysteine residues. In addition, as can be predicted from secondary structure, the quantity both of α-helixes and their amino acid residues of the subunits from TD-256 is fewer than those of common wheat. Though low molecular weight glutenin subunit (LMW-GS) and gliadin can also greatly influence flour quality, the protein structure of the HMW-GS revealed in this work can partly explain the poor flour quality of wild emmer accession TD-256.

  12. The potential benefits of low-molecular-weight heparins in cancer patients.

    PubMed

    Robert, Francisco

    2010-01-14

    Cancer patients are at increased risk of venous thromboembolism due to a range of factors directly related to their disease and its treatment. Given the high incidence of post-surgical venous thromboembolism in cancer patients and the poor outcomes associated with its development, thromboprophylaxis is warranted. A number of evidence-based guidelines delineate anticoagulation regimens for venous thromboembolism treatment, primary and secondary prophylaxis, and long-term anticoagulation in cancer patients. However, many give equal weight to several different drugs and do not make specific recommendations regarding duration of therapy. In terms of their efficacy and safety profiles, practicality of use, and cost-effectiveness the low-molecular-weight heparins are at least comparable to, and offer several advantages over, other available antithrombotics in cancer patients. In addition, data are emerging that the antithrombotics, and particularly low-molecular-weight heparins, may exert an antitumor effect which could contribute to improved survival in cancer patients when given for long-term prophylaxis. Such findings reinforce the importance of thromboprophylaxis with low-molecular-weight heparin in cancer patients.

  13. Effects of Molecular Weight on poly( -pentadecalactone) Mechanical and Thermal Properties

    SciTech Connect

    Cai, J.; Liu, C; Cai, M; Zhu, J; Zuo, F; Hsiao, B; Gross, R

    2010-01-01

    A series of poly({omega}-pentadecalactone) (PPDL) samples, synthesized by lipase catalysis, were prepared by systematic variation of reaction time and water content. These samples possessed weight-average molecular weights (M{sub w}), determined by multi-angle laser light scattering (MALLS), from 2.5 x 10{sup 4} to 48.1 x 10{sup 4}. Cold-drawing tensile tests at room temperature of PPDL samples with M{sub W} between 4.5 x 10{sup 4} and 8.1 x 10{sup 4} showed a brittle-to-ductile transition. For PPDL with M{sub W} of 8.1 x 10{sup 4}, inter-fibrillar slippage dominates during deformation until fracture. Increasing M{sub W} above 18.9 x 10{sup 4} resulted in enhanced entanglement network strength and strain-hardening. The high M{sub W} samples also exhibited tough properties with elongation at break about 650% and tensile strength about 60.8 MPa, comparable to linear high density polyethylene (HDPE). Relationships among molecular weight, Young's modulus, stress, strain at yield, melting and crystallization enthalpy (by differential scanning calorimetry, DSC) and crystallinity (from wide-angle X-ray diffraction, WAXD) were correlated for PPDL samples. Similarities and differences of linear HDPE and PPDL molecular weight dependence on their mechanical and thermal properties were also compared.

  14. Anticoagulant and antithrombotic activities of low-molecular-weight propylene glycol alginate sodium sulfate (PSS).

    PubMed

    Xin, Meng; Ren, Li; Sun, Yang; Li, Hai-hua; Guan, Hua-Shi; He, Xiao-Xi; Li, Chun-Xia

    2016-05-23

    Propylene glycol alginate sodium sulfate (PSS), a sulfated polysaccharide derivative, has been used as a heparinoid drug to prevent and treat hyperlipidemia and ischemic cardio-cerebrovascular diseases in China for nearly 30 years. To extend the applications of PSS, a series of low-molecular-weight PSSs (named FPs) were prepared by oxidative-reductive depolymerization, and the antithrombotic activities were investigated thoroughly in vitro and in vivo. The bioactivity evaluation demonstrated a positive correlation between the molecular weight and the anticoagulant and antithrombotic activities of FPs. FPs could prolong the APTT and clotting time and reduce platelet aggregation significantly. FPs could also effectively inhibit factor IIa in the presence of AT-III and HC-II. FPs decreased the wet weights and lengths of the thrombus and increased occlusion times in vivo. FP-6k, a PSS fragment with a molecular weight of 6 kDa, is an optimal antithrombotic candidate for further study and showed little chance for hemorrhagic action.

  15. Molecular modeling studies of phenoxypyrimidinyl imidazoles as p38 kinase inhibitors using QSAR and docking.

    PubMed

    Ravindra, G K; Achaiah, G; Sastry, G N

    2008-04-01

    p38 Kinase plays a vital role in inflammation mediated by tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) pathways and inhibitors of p38 kinase provide effective approach for the treatment of inflammatory diseases. Pyridinyl and pyrimidinyl imidazoles, selectively inhibit p38alpha MAP kinase, are useful in the treatment of inflammatory diseases like rheumatoid arthritis. Three dimensional quantitative structure-activity relationship studies (3D-QSAR) involving comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA) and molecular docking were performed on 44 phenoxypyrimidinyl imidazole p38 kinase inhibitors to find out the structural relationship with the activity. The best predictive CoMFA model with atom fit alignment resulted in cross-validated r(2) value of 0.553, noncross-validated r(2) value of 0.908 and standard error of estimate 0.187. Similarly the best predictive CoMSIA model was derived with q(2) of 0.508, noncross-validated r(2) of 0.894 and standard error of estimate of 0.197, comprising steric, electrostatic, hydrophobic and hydrogen bond donor fields. These models were able to predict the activity of test set molecules efficiently within an acceptable error range. GOLD and FlexX were employed to dock the inhibitors into the active site of the p38 kinase and these docking studies revealed the vital interactions and binding conformation of the inhibitors. The information rendered by 3D-QSAR models and the docking interactions may afford valuable clues to optimize the lead and design new potential inhibitors.

  16. Structural Biology and Molecular Modeling in the Design of Novel DPP-4 Inhibitors

    NASA Astrophysics Data System (ADS)

    Scapin, Giovanna

    Inhibition of dipeptidyl peptidase IV (DPP-4) is a promising new approach for the treatment of type 2 diabetes. DPP-4 is the enzyme responsible for inactivating the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), two hormones that play important roles in glucose homeostasis. The potent, orally bioavailable and highly selective small molecule DPP-4 inhibitor sitagliptin has been approved by the FDA as novel drug for the treatment of type 2 diabetes. The comparison between the binding mode of sitagliptin (a β-amino acid) and that of a second class of inhibitors (α-amino acid-based) initially led to the successful identification and design of structurally diverse and highly potent DPP-4 inhibitors. Further analysis of the crystal structure of sitagliptin bound to DPP-4 suggested that the central β-amino butanoyl moiety could be replaced by a rigid group. This was confirmed by molecular modeling, and the resulting cyclohexylamine analogs were synthesized and found to be potent DPP-4 inhibitors. However, the triazolopyrazine was predicted to be distorted in order to fit in the binding pocket, and the crystal structure showed that multiple conformations exist for this moiety. Additional molecular modeling studies were then used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Novel compounds were thus synthesized and found to be potent DPP-4 inhibitors. Two compounds in particular were designed to be highly selective against off-target "DPP-4 Activity- and/or Structure Homologues" (DASH) enzymes while maintaining potency against DPP-4.

  17. Wet-spinnability and crosslinked fibre properties of two collagen polypeptides with varied molecular weight.

    PubMed

    Tronci, Giuseppe; Kanuparti, Ramya Sri; Arafat, M Tarik; Yin, Jie; Wood, David J; Russell, Stephen J

    2015-11-01

    The formation of naturally derived materials with wet stable fibrous architectures is paramount in order to mimic the features of tissues at the molecular and microscopic scale. Here, we investigated the formation of wet-spun fibres based on collagen-derived polypeptides with comparable chemical composition and varied molecular weight. Gelatin and hydrolysed fish collagen (HFC) were selected as widely available linear amino-acidic chains of high and low molecular weight, respectively, and functionalised in the wet-spun fibre state in order to preserve the material geometry in physiological conditions. Wet-spun fibre diameter and morphology were dramatically affected depending on the polypeptide molecular weight, wet-spinning solvent (i.e. 2,2,2-trifluoroethanol and dimethyl sulfoxide) and coagulating medium (i.e. acetone and ethanol), resulting in either bulky or porous internal geometry. Dry-state tensile moduli were significantly enhanced in gelatin and HFC samples following covalent crosslinking with activated 1,3-phenylenediacetic acid (Ph) (E: 726±43-844±85MPa), compared to samples crosslinked via intramolecular carbodiimide-mediated condensation reaction (E: 588±38MPa). Resulting fibres displayed a dry diameter in the range of 238±18-355±28μm and proved to be mechanically stable (E: 230kPa) following equilibration with PBS, whilst a nearly complete degradation was observed after 5-day incubation in physiological conditions.

  18. Effect of thermal treatment on potato starch evidenced by EPR, XRD and molecular weight distribution.

    PubMed

    Bidzińska, Ewa; Michalec, Marek; Pawcenis, Dominika

    2015-12-01

    Effect of heating of the potato starch on damages of its structure was investigated by quantitative electron paramagnetic resonance (EPR) spectroscopy, X-ray diffraction and determination of the molecular weight distribution. The measurements were performed in the temperature range commonly used for starch modifications optimizing properties important for industrial applications. Upon thermal treatment, because of breaking of the polymer chains, diminishing of the average molecular weights occurred, which significantly influences generation of radicals, evidenced by EPR. For the relatively mild conditions, with heating parameters not exceeding temperature 230 °C and time of heating equal to 30 min a moderate changes of both the number of thermally generated radicals and the mean molecular weight of the starch were observed. After more drastic thermal treatment (e.g. 2 h at 230 °C), a rapid increase in the radical amount occurred, which was accompanied by significant reduction of the starch molecular size and crystallinity. Experimentally established threshold values of heating parameters should not be exceeded in order to avoid excessive damages of the starch structure accompanied by the formation of the redundant amount of radicals. This requirement is important for industrial applications, because significant destruction of the starch matrix might annihilate the positive influence of the previously performed intentional starch modification.

  19. Molecular-weight distributions of coal and petroleum asphaltenes from laser desorption/ionization experiments

    SciTech Connect

    Ana R. Hortal; Paola Hurtado; Bruno Martinez-Haya; Oliver C. Mullins

    2007-09-15

    Molecular-weight distributions (MWDs) of asphaltenes extracted from coal and petroleum have been measured in laser desorption/ionization (LDI) mass spectrometric experiments. The dried-droplet and solvent-free sample preparation methods are compared. The coal asphaltenes have a relatively narrow MWD (full width 150 amu) with an average molecular weight of 340 amu. The petroleum asphaltenes display a broader MWD (full width 300 amu) and are heavier on average (680 amu). The LDI spectra also provide evidence for the formation of noncovalent clusters of the two types of asphaltenes during the desorption process. Petroleum and coal asphaltenes exhibit aggregation as do large model polycyclic aromatic hydrocarbons (PAHs) with five or more fused rings also included in the study. Smaller PAHs (pyrene) exhibit less aggregation, especially when alkane-chain substituents are incorporated to the molecular structure. This indicates that asphaltenes possess large PAHs and, according to the relatively small molecular weights observed, that there is a preponderance of asphaltene molecules with only a single fused ring system. The coal asphaltenes present a significantly smaller propensity toward aggregation than their crude oil counterparts. This finding, coupled with the fact that (1) alkanes inhibit aggregation in LDI and (2) petroleum asphaltenes possess much more alkane carbon, indicates that coal asphaltenes have smaller PAHs on average than petroleum asphaltenes. This is further corroborated by the stronger ultraviolet absorbance of the coal asphaltenes at wavelengths shorter than 400 nm. 32 refs., 8 figs.

  20. Cellular Viscosity in Prokaryotes and Thermal Stability of Low Molecular Weight Biomolecules.

    PubMed

    Cuecas, Alba; Cruces, Jorge; Galisteo-López, Juan F; Peng, Xiaojun; Gonzalez, Juan M

    2016-08-23

    Some low molecular weight biomolecules, i.e., NAD(P)H, are unstable at high temperatures. The use of these biomolecules by thermophilic microorganisms has been scarcely analyzed. Herein, NADH stability has been studied at different temperatures and viscosities. NADH decay increased at increasing temperatures. At increasing viscosities, NADH decay rates decreased. Thus, maintaining relatively high cellular viscosity in cells could result in increased stability of low molecular weight biomolecules (i.e., NADH) at high temperatures, unlike what was previously deduced from studies in diluted water solutions. Cellular viscosity was determined using a fluorescent molecular rotor in various prokaryotes covering the range from 10 to 100°C. Some mesophiles showed the capability of changing cellular viscosity depending on growth temperature. Thermophiles and extreme thermophiles presented a relatively high cellular viscosity, suggesting this strategy as a reasonable mechanism to thrive under these high temperatures. Results substantiate the capability of thermophiles and extreme thermophiles (growth range 50-80°C) to stabilize and use generally considered unstable, universal low molecular weight biomolecules. In addition, this study represents a first report, to our knowledge, on cellular viscosity measurements in prokaryotes and it shows the dependency of prokaryotic cellular viscosity on species and growth temperature.

  1. Exploration of Novel Human Tyrosinase Inhibitors by Molecular Modeling, Docking and Simulation Studies.

    PubMed

    Hassan, Mubashir; Ashraf, Zaman; Abbas, Qamar; Raza, Hussain; Seo, Sung-Yum

    2016-04-21

    Research studies on human tyrosinase inhibitors and exploration for better cytotoxic agents remain an important line in drug discovery and development at the present time. Recently, multiple inhibitors are being used to cure melanogenesis by targeting human tyrosinase. A series of coumarin (C1-C9)-, thymol (T1-T8)- and vanillin (V1-V8)-based derivatives have been theoretically analyzed for their inhibitory effects against human tyrosinase. The crystal structure of human tyrosinase is not available in Protein Data Bank. Therefore, homology modeling approach was used to predict three-dimensional (3D) crystal structure of human tyrosinase. The reliability and efficacy of predicted 3D structure were validated by using Ramachandran plots which indicate that 95.01 % residues are present in favored regions. Moreover, multiple computational approaches such as molecular docking and molecular dynamic (MD) simulation along with various online tools were employed to screen the best inhibitor against melanogenesis. The results revealed that V7 and C9 compounds showed significant binding energy values (-7.79 and -7.40 kcal/mol, respectively) compared with the standard drugs such as kojic acid (-4.21 kcal/mol) and arbutin (-4.62 kcal/mol). Moreover, MD simulation results also justified that V7 showed little fluctuations throughout the simulation period as depicted by the root mean square deviation and root mean square fluctuation graphs. Thus, the present in silico study provides a deeper insight into the structural attributes of V7 compound and its overall molecular interactions against human tyrosinase and gives a hypothetical gateway to use this compound as a potential inhibitor against melanogenesis.

  2. WeGET: predicting new genes for molecular systems by weighted co-expression

    PubMed Central

    Szklarczyk, Radek; Megchelenbrink, Wout; Cizek, Pavel; Ledent, Marie; Velemans, Gonny; Szklarczyk, Damian; Huynen, Martijn A.

    2016-01-01

    We have developed the Weighted Gene Expression Tool and database (WeGET, http://weget.cmbi.umcn.nl) for the prediction of new genes of a molecular system by correlated gene expression. WeGET utilizes a compendium of 465 human and 560 murine gene expression datasets that have been collected from multiple tissues under a wide range of experimental conditions. It exploits this abundance of expression data by assigning a high weight to datasets in which the known genes of a molecular system are harmoniously up- and down-regulated. WeGET ranks new candidate genes by calculating their weighted co-expression with that system. A weighted rank is calculated for human genes and their mouse orthologs. Then, an integrated gene rank and p-value is computed using a rank-order statistic. We applied our method to predict novel genes that have a high degree of co-expression with Gene Ontology terms and pathways from KEGG and Reactome. For each query set we provide a list of predicted novel genes, computed weights for transcription datasets used and cell and tissue types that contributed to the final predictions. The performance for each query set is assessed by 10-fold cross-validation. Finally, users can use the WeGET to predict novel genes that co-express with a custom query set. PMID:26582928

  3. Down-regulation of c-myc gene expression with induction of high molecular weight DNA fragments by fluorodeoxyuridine.

    PubMed

    Li, Z R; Yin, M B; Arredondo, M A; Schöber, C; Rustum, Y M

    1994-07-19

    5-Fluoro-2'-deoxyuridine (FdUrd), a potent inhibitor of thymidylate synthase, induces extensive bulk DNA damage at drug concentrations that produce significant in vitro growth inhibition of human ileocecal carcinoma (HCT-8) cells. Constant- and pulsed-field gel electrophoresis (CFGE and PFGE), to detect size distribution of DNA double-strand breaks and repair kinetics, in parallel with northern and western blot analyses, to quantitate c-myc gene and protein expression, were utilized to analyze drug effects. At 24-hr post in vitro drug treatment, when maximum bulk DNA damage was detected, FdUrd produced a broad range of high molecular weight DNA fragments, clustering between 0.1 and 5.7 megabases in size, and resulted in a decrease in the level of c-myc transcripts and protein with no significant effect on the level of v-myc and H-ras. These effects preceded the observed cellular growth inhibition. Addition of the reduced folate leucovorin potentiated the effects induced by FdUrd, indicating that thymidylate synthase inhibition is an important initial step in drug effect followed by DNA fragmentation and suppression of c-myc expression. Changes in the integrity of the genetic materials and regulatory genes occurred prior to the observed cell growth inhibition by FdUrd, suggesting that these molecular alterations by FdUrd may be associated with subsequent FdUrd-induced cell growth inhibition.

  4. Inhibition of Helicobacter pylori adhesion to Kato III cells by intact and low molecular weight acharan sulfate.

    PubMed

    Sim, Joon-Soo; Hahn, Bum-Soo; Im, A-Rang; Park, Youmie; Shin, Ji-Eun; Bae, Eun-Ah; Kim, Dong-Hyun; Kim, Yeong Shik

    2011-08-01

    We investigated the inhibitory activity of glycosaminoglycans (GAGs) in terms of growth, adhesion, and VacA vacuolation of Helicobacter pylori. Intact acharan sulfate (AS, MW:114 kDa) potently inhibited H. pylori adhesion to Kato III cells with IC(50) value of 1.4 mg/mL, while other GAGs did not show any inhibitory activity except for heparin which is a well-known inhibitor of H. pylori adhesion. To investigate whether low molecular weight acharan sulfate (LMWAS) can inhibit H. pylori adhesion, we performed chemical depolymerization of AS by radical reactions to obtain LMWAS. Its physicochemical properties were characterized by high-performance size exclusion chromatography (HPSEC), agarose gel electrophoresis, disaccharide compositional analysis after digestion with heparinase II, and (1)H-NMR spectroscopy. The most potent molecular size of LMWAS was 3 kDa with IC(50) value of 32 μg/mL, which is 44-fold more potent than intact AS. These results suggest that AS as well as other GAGs can be chemically depolymerized by free radicals and LMWAS compared to intact AS can be applied as a pharmaceutical candidate in order to inhibit H. pylori adhesion to Kato III cells.

  5. Purification and biochemical properties of SDS-stable low molecular weight alkaline serine protease from Citrullus colocynthis.

    PubMed

    Khan, Muhammad Bashir; Khan, Hidayatullah; Shah, Muhammad Usman; Khan, Sanaullah

    2016-01-01

    A low molecular weight serine protease from seeds of Citrullus colocynthis was purified to electrophoretic homogeneity with high level of catalytic efficiency (22,945 M(-1) S(-1)). The enzyme was a monomer with molecular mass of 25 kDa estimated by SDS-PAGE. The enzyme was highly active over a pH range of 6.5-9.0 and temperature range of 20-80 °C, with maximum activity at pH 7.5 and at 50 °C. The K(m) and K(cat) were 73 μg/mL and 67/s, respectively. The enzyme was strongly inhibited by PMSF, moderately by soybean trypsin inhibitor, indicating that the enzyme was a serine protease. The enzyme retained 86 and 73% of its activity in the presence of urea and DTT, respectively, and its activity was slightly enhanced in the presence of anionic detergent (SDS). Thus, the enzyme is a novel SDS-stable protease with high catalytic efficiency over wide ranges of pH and temperature which is commercially promising for various industrial applications.

  6. Key Structures and Interactions for Binding of Mycobacterium tuberculosis Protein Kinase B Inhibitors from Molecular Dynamics Simulation.

    PubMed

    Punkvang, Auradee; Kamsri, Pharit; Saparpakorn, Patchreenart; Hannongbua, Supa; Wolschann, Peter; Irle, Stephan; Pungpo, Pornpan

    2015-07-01

    Substituted aminopyrimidine inhibitors have recently been introduced as antituberculosis agents. These inhibitors show impressive activity against protein kinase B, a Ser/Thr protein kinase that is essential for cell growth of M. tuberculosis. However, up to now, X-ray structures of the protein kinase B enzyme complexes with the substituted aminopyrimidine inhibitors are currently unavailable. Consequently, structural details of their binding modes are questionable, prohibiting the structural-based design of more potent protein kinase B inhibitors in the future. Here, molecular dynamics simulations, in conjunction with molecular mechanics/Poisson-Boltzmann surface area binding free-energy analysis, were employed to gain insight into the complex structures of the protein kinase B inhibitors and their binding energetics. The complex structures obtained by the molecular dynamics simulations show binding free energies in good agreement with experiment. The detailed analysis of molecular dynamics results shows that Glu93, Val95, and Leu17 are key residues responsible to the binding of the protein kinase B inhibitors. The aminopyrazole group and the pyrimidine core are the crucial moieties of substituted aminopyrimidine inhibitors for interaction with the key residues. Our results provide a structural concept that can be used as a guide for the future design of protein kinase B inhibitors with highly increased antagonistic activity.

  7. Synthesis of the iron-molybdenum cofactor of nitrogenase is inhibited by a low-molecular-weight metabolite of Klebsiella pneumoniae.

    PubMed

    Downs, D M; Ludden, P W; Shah, V K

    1990-10-01

    The in vitro synthesis of the iron-molybdenum cofactor nitrogenase was inhibited by a low-molecular-weight factor. This inhibitory factor was present in the membrane extracts of wild-type and nif mutant strains of Klebsiella pneumoniae that were grown under conditions that either repressed or derepressed nitrogenase expression. In vitro, the inhibition was specific for the NifB protein. Addition of this factor to K. pneumoniae cells at various times during nif derepression decreased nitrogenase activity, presumably through inhibition of iron-molybdenum cofactor synthesis. The inhibitor was purified by solvent extraction and chromatography on DEAE-cellulose, silica gel, and aluminum oxide columns.

  8. Molecular interaction of 2-mercaptobenzimidazole with catalase reveals a potentially toxic mechanism of the inhibitor.

    PubMed

    Teng, Yue; Zou, Luyi; Huang, Ming; Zong, Wansong

    2014-12-01

    2-Mercaptobenzimidazole (MBI) is widely utilized as a corrosion inhibitor, copper-plating brightener and rubber accelerator. The residue of MBI in the environment possesses a potential risk to human health. In this work, the toxic interaction of MBI with the important antioxidant enzyme catalase (CAT) was investigated using spectroscopic and molecular docking methods under physiological conditions. MBI can spontaneously bind with CAT with one binding site through hydrogen bonds and van der Waals forces to form MBI-CAT complex. The molecular docking study revealed that MBI bound into the CAT interface of chains B and C, which led to some conformational and microenvironmental changes of CAT and further resulted in the inhibition of CAT activity. This present study provides direct evidence at a molecular level to show that exposure to MBI could induce changes in the structure and function of the enzyme CAT.

  9. Isolation of high molecular weight plant nuclear DNA suitable for use in recombinant DNA technology.

    PubMed

    Kiss, T; Solymosy, F

    1987-01-01

    Nuclei isolated from leaf cells of broad bean (Vicia faba L) by a newly developed method based on the use of citric acid in the isolation medium and flotation on a Percoll cushion yielded high molecular weight plant nuclear DNA which was suitable for (i) analysis by restriction endonucleases, (ii) molecular cloning and (iii) genomic blot hybridization. Starting from nuclear preparations obtained by this method, U2 small nuclear RNA-specific DNA sequences were detected in Vicia faba L. This is the first report on the demonstration of small nuclear RNA-specific DNA sequences in plant material.

  10. Raman study of uniaxial deformation of single-crystal mats of ultrahigh molecular weight linear polyethylene

    NASA Astrophysics Data System (ADS)

    Zavgorodnev, Yu V.; Chvalun, S. N.; Nikolaeva, G. Yu; Sagitova, E. A.; Pashinin, P. P.; Gordeyev, S. A.; Prokhorov, K. A.

    2015-03-01

    We present for the first time a Raman spectroscopic study of the deformation process of solution-crystallized single-crystal mats of ultrahigh molecular weight linear polyethylene (UHMW PE). We study the deformed regions of the films, drawn only until the formation of the neck, and the films of much higher draw ratios, just before rupture starts. For comparison, we have also carried out Raman investigations of films produced by compression of UHMW PE powder. We have found that the uniaxial molecular orientation in the neck region of the single-crystal mat films develops more slowly as compared to the films, prepared by compression of the UHMW PE powder.

  11. A combinative effect of low-molecular-weight heparin and intermittent pneumatic compression device for thrombosis prevention during laparoscopic fundoplication.

    PubMed

    Kiudelis, Mindaugas; Gerbutavicius, Rolandas; Gerbutaviciene, Rima; Griniūte, Rasa; Mickevicius, Antanas; Endzinas, Zilvinas; Pundzius, Juozas

    2010-01-01

    BACKGROUND. Venous thromboembolism is known to be an important social and health care problem because of its high incidence among patients who undergo surgery. For instance, 20-30% of patients develop this problem after general surgical operations, while 5.5% of patients have this complication when laparoscopic fundoplications are performed without any prophylaxis. The aim of our study was to evaluate the hypocoagulation effect of the following treatments during and after laparoscopic fundoplication: a) intermittent pneumatic compression (IPC) and b) combination of low-molecular-weight heparin (LMWH) and IPC. MATERIAL AND METHODS. The study was performed on 20 consecutive patients who were randomized into two groups. The first group received IPC during operation, the second group received IPC during operation and LMWH before operation. Plasma prothrombin fragment F1+2 (F1+2), thrombin-antithrombin complex (TAT) - markers of thrombogenesis - and plasma free tissue factor pathway inhibitor (fTFPI) - a marker of hypocoagulation effect - were measured 1 h before, during, and after the laparoscopic operation. RESULTS. In the IPC group, plasma F1+2 and TAT levels increased significantly during and after laparoscopic gastrofundoplication. In the IPC+LMWH group, F1+2 and plasma TAT levels did not change during or after the operation. fTFPI levels significantly increased during and after the operation in the IPC+LMWH group; however, fTFPI levels did not change during or after the laparoscopic operation in the IPC group. CONCLUSIONS. A combination of low-molecular-weight heparin and intermittent pneumatic compression during laparoscopic fundoplication caused hypocoagulation effect in the patients, which was not observed in the patients who were treated with intermittent pneumatic compression alone.

  12. Temperature, Molecular Weight, and Concentration Dependences of Thermal Diffusion for Ethylene Glycol Oligomers and Crown Ethers

    NASA Astrophysics Data System (ADS)

    Maeda, Kousaku; Kita, Rio; Shinyashiki, Naoki; Yagihara, Shin

    The Soret coefficient ST of ethylene glycol oligomers (EGOs) and crown ethers (CEs) in water were obtained by thermal diffusion forced Rayleigh scattering by changing the temperature, molecular weight, and concentration. The effect of a hydroxyl group on the EGOs and the effect of the cyclic structure of CEs on the thermal diffusion were determined systematically by changing the molecular weights of the EGOs and CEs. For dilute aqueous solutions, EGOs and CEs, except EG, show positive ST values that decrease with increasing temperature, which is similar to the results of previous studies on mixtures of water and organic solvents. The temperature dependence of ST changes its behavior from negative to positive with decreasing number of repeating units of EGOs. This behavior is related to the increase in the number density of the hydroxyl group. The ST values of EG show two different concentration regions, namely, the low concentration (0-2 wt %) and high concentration (2-100 wt %) regions.

  13. Evaluating nephrotoxicity of high-molecular-weight organic compounds in drinking water from lignite aquifers

    USGS Publications Warehouse

    Bunnell, J.E.; Tatu, C.A.; Lerch, H.E.; Orem, W.H.; Pavlovic, N.

    2007-01-01

    High-molecular-weight organic compounds such as humic acids and/or fulvic acids that are naturally mobilized from lignite beds into untreated drinking-water supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN) and cancer of the renal pelvis. A lab investigation was undertaken in order to assess the nephrotoxic potential of such organic compounds using an in vitro tissue culture model. Because of the infeasibility of exposing kidney tissue to low concentrations of organics for years in the lab, tangential flow ultrafiltration was employed to hyperconcentrate samples suitable for discerning effects in the short time frames necessitated by tissue culture systems. Effects on HK-2 kidney cells were measured using two different cell proliferation assays (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high-molecular-weight organics produced excess cell death or proliferation depending on concentration and duration of exposure. Copyright ?? Taylor & Francis Group, LLC.

  14. Role of laccase and low molecular weight metabolites from Trametes versicolor in dye decolorization.

    PubMed

    Moldes, Diego; Fernández-Fernández, María; Sanromán, M Ángeles

    2012-01-01

    The studies regarding decolorization of dyes by laccase may not only inform about the possible application of this enzyme for environmental purposes, but also may provide important information about its reaction mechanism and the influence of several factors that could be involved. In this paper, decolorization of crystal violet and phenol red was carried out with different fractions of extracellular liquids from Trametes versicolor cultures, in order to describe the role of laccase in this reaction. Moreover, the possible role of the low molecular weight metabolites (LMWMs) also produced by the fungus was evaluated. The results confirm the existence of a nonenzymatic decolorization factor, since the nonprotein fraction of the extracellular liquids from cultures of T. versicolor has shown decolorization capability. Several experiments were performed in order to identify the main compounds related to this ability, which are probably low molecular weight peroxide compounds.

  15. [Sequencing of low-molecular-weight DNA in blood plasma of irradiated rats].

    PubMed

    Vasilieva, I N; Bespalov, V G; Zinkin, V N; Podgornaya, O I

    2015-01-01

    Extracellular low-molecular-weight DNA in blood of irradiated rats was sequenced for the first time. The screening of sequences in the DDBJ database displayed homology of various parts of the rodent genome. Sequences of low-molecular-weight DNA in rat's plasma are enriched with G/C pairs and long interspersed elements relative to rat genome. DNA sequences in blood of rats irradiated at the doses of 8 and 100 Gy have marked distinctions. Data of sequencing of extracellular DNA from normal humans and with pathology were analyzed. DNA sequences of irradiated rats differ from the human ones by a wealth of long interspersed elements. This new knowledge lays the foundation for development of minimally invasive technologies of diagnosing the probability of pathology and controlling the adaptive resources of people in extreme environments.

  16. Friction and wear of polyethylene oxide polymer having a range of molecular weights

    NASA Technical Reports Server (NTRS)

    Buckley, D. H.

    1978-01-01

    Sliding friction and wear experiments were conducted at light loads (25 to 250 g) with various molecular weights of the polyethylene oxide polymer sliding on itself and iron. Results of the experimental investigation indicate that: (1) the coefficient of friction for the polymer decreases with increasing molecular weight; (2) friction coefficient is higher for the polymer sliding on itself than it is for the polymer sliding on iron; (3) at sufficiently high loads localized surface melting occurs and the friction coefficient is the same for the polymer sliding on itself and iron; (4) fracture cracks develop in the sliding wear track at higher but not lower sliding velocities, reflecting a strain rate sensitivity to crack initiation, and (5) the friction coefficient for the polymer sliding on iron increases with the formation of a polymer film on the iron surface.

  17. High molecular weight bioemulsifiers, main properties and potential environmental and biomedical applications.

    PubMed

    Mnif, Inès; Ghribi, Dhouha

    2015-05-01

    High molecular weight bioemulsifiers are amphipathic polysaccharides, proteins, lipopolysaccharides, lipoproteins, or complex mixtures of these biopolymers, produced by a wide variety of microorganisms. They are characterized by highly structural diversity and have the ability to decrease the surface and interfacial tension at the surface and interface respectively and/or emulsify hydrophobic compounds. Emulsan, fatty acids, phospholipids, neutral lipids, exopolysaccharides, vesicles and fimbriae are among the most popular high molecular weight bioemulsifiers. They have great physic-chemical properties like tolerance to extreme conditions of pH, temperature and salinity, low toxicity and biodegradability. Owing their emulsion forming and breaking capacities, solubilization, mobilization and dispersion activities and their viscosity reduction activity; they possess great environmental application as enhancer of hydrocarbon biodegradation and for microbial enhanced oil recovery. Besides, they are applied in biomedical fields for their antimicrobial and anti-adhesive activities and involvement in immune responses.

  18. HPMA-oligolysine copolymers for gene delivery: optimization of peptide length and polymer molecular weight.

    PubMed

    Johnson, Russell N; Chu, David S H; Shi, Julie; Schellinger, Joan G; Carlson, Peter M; Pun, Suzie H

    2011-10-30

    Polycations are one of the most frequently used classes of materials for non-viral gene transfer in vivo. Several studies have demonstrated a sensitive relationship between polymer structure and delivery activity. In this work, we used reverse addition-fragmentation chain transfer (RAFT) polymerization to build a panel of N-(2-hydroxypropyl)methacrylamide (HPMA)-oligolysine copolymers with varying peptide length and polymer molecular weight. The panel was screened for optimal DNA-binding, colloidal stability in salt, high transfection efficiency, and low cytotoxicity. Increasing polyplex stability in PBS correlated with increasing polymer molecular weight and decreasing peptide length. Copolymers containing K(5) and K(10) oligocations transfected cultured cells with significantly higher efficiencies than copolymers of K(15). Four HPMA-oligolysine copolymers were identified that met the desired criteria. Polyplexes formed with these copolymers demonstrated both salt stability and transfection efficiencies on-par with poly(ethylenimine) PEI in cultured cells.

  19. Extraction of high-molecular-weight genomic DNA for long-read sequencing of single molecules.

    PubMed

    Mayjonade, Baptiste; Gouzy, Jérôme; Donnadieu, Cécile; Pouilly, Nicolas; Marande, William; Callot, Caroline; Langlade, Nicolas; Muños, Stéphane

    2016-10-01

    De novo sequencing of complex genomes is one of the main challenges for researchers seeking high-quality reference sequences. Many de novo assemblies are based on short reads, producing fragmented genome sequences. Third-generation sequencing, with read lengths >10 kb, will improve the assembly of complex genomes, but these techniques require high-molecular-weight genomic DNA (gDNA), and gDNA extraction protocols used for obtaining smaller fragments for short-read sequencing are not suitable for this purpose. Methods of preparing gDNA for bacterial artificial chromosome (BAC) libraries could be adapted, but these approaches are time-consuming, and commercial kits for these methods are expensive. Here, we present a protocol for rapid, inexpensive extraction of high-molecular-weight gDNA from bacteria, plants, and animals. Our technique was validated using sunflower leaf samples, producing a mean read length of 12.6 kb and a maximum read length of 80 kb.

  20. Influence of molecular weight on the resistance of polylactide fibers by radiation sterilization

    SciTech Connect

    Horacek, I.; Kudlacek, L. . Dept. of Fibres and Textile Chemistry)

    1993-10-05

    The mechanical properties and in vitro degradability of poly(L-lactide) fibers with different average molecular weights, prepared by a dry spinning-hot drawing process from CHCl[sub 3] solutions, were studied in relation to the [gamma]-irradiation dose. In the range of molecular weight of 1.6--3.6 [times] 10[sup 5], no differences were found in the relative decrease of tensile strength after irradiation of 25 kGy. Changes of the elongation at break are discussed in terms of a network solution theory. In vitro degradation of the fibers is also discussed in network solution theory terms. Regardless of the courses of degradation curves, it may be stated that all prepared fibers could be sterilized by [gamma]-rays and the rate of degradation was not affected by the irradiation dose.

  1. Characteristics of Precipitation-formed Polyethylene Glycol Microgels Are Controlled by Molecular Weight of Reactants

    PubMed Central

    Thompson, Susan; Stukel, Jessica; AlNiemi, Abrar; Willits, Rebecca Kuntz

    2013-01-01

    This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer several advantages over traditional microsphere fabrication techniques. Contrary to emulsion, suspension, and dispersion techniques, microgels formed by precipitation are of uniform shape and size, i.e. low polydispersity index, without the use of organic solvents or stabilizers. The mild conditions of the precipitation reaction, customizable properties of the microgels, and low viscosity for injections make them applicable for in vivo purposes. Unlike other fabrication techniques, microgel characteristics can be modified by changing the starting polymer molecular weight. Increasing the starting PEG molecular weight increased microgel diameter and swelling ratio. Further modifications are suggested such as encapsulating molecules during microgel crosslinking. Simple adaptations to the PEG microgel building blocks are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds. PMID:24378988

  2. Characterization and Immunological Evaluation of Low-Molecular- Weight Alginate Derivatives.

    PubMed

    Xu, Xu; Bi, Decheng; Wan, Min

    2016-01-01

    Alginate is a naturally occurring acidic linear polysaccharide obtained from marine brown seaweed. Low molecular weight structurally diverse derivatives and oligosaccharides derived from alginate have shown various tremendous biological and pharmacological activities. It has been demonstrated that immuno-inflammation is involved in many prevalent human diseases, such as cancer, severe infection and neurodegeneration. Given the activities of marine natural products in the regulation of immune responses, increasing efforts are being made toward the development of lowmolecular- weight natural compounds that aid in the prevention and treatment of immune- and inflammatory-related diseases. In this review, we describe the development of chemical modification and molecular depolymerization methods that modify the physicochemical and biological characteristics of alginate. Additionally, current progress in research on immuno-inflammatory, anti-neurodegenerative and anti-tumor activities of alginate derivatives is highlighted.

  3. Binding of pyrene to aquatic and commercial humic substances: The role of molecular weight and aromaticity

    USGS Publications Warehouse

    Chin, Y.-P.; Aiken, G.R.; Danielsen, K.M.

    1997-01-01

    The binding of pyrene to a number of humic substances isolated from various aquatic sources and a commercial humic acid was measured using the solubility enhancement method. The humic materials used in this study were characterized by various spectroscopic and liquid chromatography methods. A strong correlation was observed between the pyrene binding coefficient, K(doc), and the molecular weights, molar absorptivities at 280 nm, and aromaticity of the aquatic humic substances. Binding of pyrene to the commercial humic acid, however, was significantly stronger and did not obey the relationships observed between K(doc) and the chemical properties of the aquatic humic substrates. These results suggest that the molecular weight and the aromatic content of the humic substrates exert influences on the binding of nonpolar and planar aromatic molecules and that the physicochemical properties of both humic materials and organic solutes are important in controlling the speciation of nonpolar organic contaminants in natural waters.

  4. High molecular weight DNA assembly in vivo for synthetic biology applications.

    PubMed

    Juhas, Mario; Ajioka, James W

    2017-05-01

    DNA assembly is the key technology of the emerging interdisciplinary field of synthetic biology. While the assembly of smaller DNA fragments is usually performed in vitro, high molecular weight DNA molecules are assembled in vivo via homologous recombination in the host cell. Escherichia coli, Bacillus subtilis and Saccharomyces cerevisiae are the main hosts used for DNA assembly in vivo. Progress in DNA assembly over the last few years has paved the way for the construction of whole genomes. This review provides an update on recent synthetic biology advances with particular emphasis on high molecular weight DNA assembly in vivo in E. coli, B. subtilis and S. cerevisiae. Special attention is paid to the assembly of whole genomes, such as those of the first synthetic cell, synthetic yeast and minimal genomes.

  5. Analysis of heterogeneity in molecular weight and shape by analytical ultracentrifugation using parallel distributed computing.

    PubMed

    Demeler, Borries; Brookes, Emre; Nagel-Steger, Luitgard

    2009-01-01

    A computational approach for fitting sedimentation velocity experiments from an analytical ultracentrifuge in a model-independent fashion is presented. This chapter offers a recipe for obtaining high-resolution information for both the shape and the molecular weight distributions of complex mixtures that are heterogeneous in shape and molecular weight and provides suggestions for experimental design to optimize information content. A combination of three methods is used to find the solution most parsimonious in parameters and to verify the statistical confidence intervals of the determined parameters. A supercomputer implementation with a MySQL database back end is integrated into the UltraScan analysis software. The UltraScan LIMS Web portal is used to perform the calculations through a Web interface. The performance and limitations of the method when employed for the analysis of complex mixtures are demonstrated using both simulated data and experimental data characterizing amyloid aggregation.

  6. Characteristics of precipitation-formed polyethylene glycol microgels are controlled by molecular weight of reactants.

    PubMed

    Thompson, Susan; Stukel, Jessica; AlNiemi, Abrar; Willits, Rebecca Kuntz

    2013-12-23

    This work describes the formation of poly(ethylene glycol) (PEG) microgels via a photopolymerized precipitation reaction. Precipitation reactions offer several advantages over traditional microsphere fabrication techniques. Contrary to emulsion, suspension, and dispersion techniques, microgels formed by precipitation are of uniform shape and size, i.e. low polydispersity index, without the use of organic solvents or stabilizers. The mild conditions of the precipitation reaction, customizable properties of the microgels, and low viscosity for injections make them applicable for in vivo purposes. Unlike other fabrication techniques, microgel characteristics can be modified by changing the starting polymer molecular weight. Increasing the starting PEG molecular weight increased microgel diameter and swelling ratio. Further modifications are suggested such as encapsulating molecules during microgel crosslinking. Simple adaptations to the PEG microgel building blocks are explored for future applications of microgels as drug delivery vehicles and tissue engineering scaffolds.

  7. Simulated dynamic response of a multi-stage compressor with variable molecular weight flow medium

    NASA Technical Reports Server (NTRS)

    Babcock, Dale A.

    1995-01-01

    A mathematical model of a multi-stage compressor with variable molecular weight flow medium is derived. The modeled system consists of a five stage, six cylinder, double acting, piston type compressor. Each stage is followed by a water cooled heat exchanger which serves to transfer the heat of compression from the gas. A high molecular weight gas (CFC-12) mixed with air in varying proportions is introduced to the suction of the compressor. Condensation of the heavy gas may occur in the upper stage heat exchangers. The state equations for the system are integrated using the Advanced Continuous Simulation Language (ACSL) for determining the system's dynamic and steady state characteristics under varying operating conditions.

  8. Molecular weight of polydisperse icodextrin effects its oncotic contribution to water transport.

    PubMed

    Nishimura, Kohei; Kamiya, Yohei; Miyamoto, Keiichi; Nomura, Shinsuke; Horiuchi, Takashi

    2008-01-01

    Icodextrin, a mixture of polysaccharides of alpha-(1 --> 4) polyglucopyranose having 10% branched chains, is clinically available as a D-glucose substitute for peritoneal dialysis (PD). Due to the high intraperitoneal retention time of this glucose polymer (GP), water transport from the vessels to the peritoneal cavity is prolonged even in PD patients with high peritoneal permeability. The purpose of this study was to elucidate why 7.5% icodextrin solution has such a broad distribution of molecular weights. A gel permeation chromatography study indicated that the average molecular weight was about 18.0 kDa in terms of number average (Mn) and 31.3 kDa in terms of weight average (Mw), respectively, resulting in a polydispersity index (Mn/Mw) of 1.74. Five fractions of GP having Mn values of 41.3, 19.3, 8.3, 3.8, and 2.1 kDa, respectively, produced 0.24, 0.49, 0.50, 0.08, and 0.03 mOsmol/kg H2O of colloid osmotic pressure. Water transport through a membrane having a molecular cutoff of 15 kDa was simulated using the mass transfer coefficient and reflection coefficient for each fraction. Fractions with Mn values of 19.3 and 8.3 kDa contributed to water transport dominantly (approximately 76%), while only 18%, 5%, and 3% of total water removal was contributed by fractions with Mn values of 41.3, 3.8 and 2.1 kDa, respectively. As a result of enzymatic degradation for 10 h by 2, 10, or 20 U/l alpha-amylase, a decrease in the high molecular weight zone (40-60 kDa) and a rise in the low molecular weight zone (1-2 kDa) were seen with few change in the distribution profile between 4 and 30 kDa. These results suggested that fractions in the molecular range between 8.3 and 19.3 kDa, where the distribution profile was less influenced by enzymatic degradation, preferably contributed to water transport.

  9. Low molecular weight PEIs modified by hydrazone-based crosslinker and betaine as improved gene carriers.

    PubMed

    Fang, Gang; Zeng, Fang; Yu, Changmin; Wu, Shuizhu

    2014-10-01

    Low-molecular-weight polyethyleneimine (LMW PEI) exhibits poorer transfection efficiency but lower cytotoxicity compared to high-molecular-weight polyethyleneimine (such as PEI 25kDa). To enhance the gene transfection performance of LMW PEI, we herein demonstrate a new strategy for modifying LMW PEI. A crosslinker containing an acid-labile hydrazone bond (hydrazone-based crosslinker) was synthesized and used to crosslink PEI 1.8kDa and convert it into higher-molecular-weight polycations. And the crosslinked polycations were further modified by incorporating a betaine monomer [N,N-dimethyl(acrylamidopropyl)ammonium propane sulfonate, DMAAPS] onto their surfaces. The molar percentages of the incorporated betaine molecules to amino groups on the polycations were determined as 21.2%, 36.0% and 77.2%, respectively. Molecular weights of the modified polycations were measured using capillary viscometry at pH 7.4 and 5.0, respectively, and the degradation of the polymers in acidic solution was confirmed. The PEIs modified with hydrazone and betaine (PEI-Hdz-DMAAPS) exhibit much lower cytotoxicity than PEI 25K, and they also show no or little hemolytic effect with their hemolysis rates around 5%. PEI-Hdz-DMAAPS21.2%/DNA and PEI-Hdz-DMAAPS36.0%/DNA complexes exhibit high transfection efficiencies, which are comparable to or higher than that of PEI 25K/DNA complex in the absence or presence of 10% serum. With these improved gene delivery properties, the PEI-Hdz-DMAAPS samples have great potential for serving as efficient gene carriers. This strategy may provide some insights for constructing some other biocompatible materials.

  10. Studies on the murine Ss protein. I. Purification, molecular weight, and subunit structure

    PubMed Central

    1975-01-01

    The murine Ss protein has been isolated and purified. Using specific antisera, the radiolabeled protein has a mol wt of 120,000 in sodium dodecyl sulfate polyacrylamide gels. It is composed of two basic subunits of 23,000 and 14,000 daltons. The smaller molecular weight subunit contains a single disulfide bridge, is devoid of carbohydrate, and may represent the murine equivalent of beta2-microglobulin. PMID:809530

  11. Development of an extremely wear-resistant ultra high molecular weight polyethylene for total hip replacements.

    PubMed

    McKellop, H; Shen, F W; Lu, B; Campbell, P; Salovey, R

    1999-03-01

    Osteolysis induced by ultra high molecular weight polyethylene wear debris is one of the primary factors limiting the lifespan of total hip replacements. Crosslinking polyethylene is known to improve its wear resistance in certain industrial applications, and crosslinked polyethylene acetabular cups have shown improved wear resistance in two clinical studies. In the present study, crosslinked polyethylene cups were produced by two methods. Chemically crosslinked cups were produced by mixing a peroxide with ultra high molecular weight polyethylene powder and then molding the cups directly to shape. Radiation-crosslinked cups were produced by exposing conventional extruded ultra high molecular weight polyethylene bar stock to gamma radiation at various doses from 3.3 to 100 Mrad (1 Mrad = 10 kGy), remelting the bars to extinguish residual free radicals (i.e., to minimize long-term oxidation), and then machining the cups by conventional techniques. In hip-joint simulator tests lasting as long as 5 million cycles, both types of cross-linked cups exhibited dramatically improved resistance to wear. Artificial aging of the cups by heating for 30 days in air at 80 degrees C induced oxidation of the chemically crosslinked cups. However, a chemically crosslinked cup that was aged 2.7 years at room temperature had very little oxidation. Thus, whether substantial oxidation of chemically crosslinked polyethylene would occur at body temperature remains unclear. The radiation-crosslinked remelted cups exhibited excellent resistance to oxidation. Because crosslinking can reduce the ultimate tensile strength, fatigue strength, and elongation to failure of ultra high molecular weight polyethylene, the optimal crosslinking dose provides a balance between these physical properties and the wear resistance of the implant and might substantially reduce the incidence of wear-induced osteolysis with total hip replacements.

  12. Crosslinker-Induced Effects on the Gelation Pathway of a Low Molecular Weight Hydrogel.

    PubMed

    Noteborn, Willem E M; Zwagerman, Damy N H; Talens, Victorio Saez; Maity, Chandan; van der Mee, Lars; Poolman, Jos M; Mytnyk, Serhii; van Esch, Jan H; Kros, Alexander; Eelkema, Rienk; Kieltyka, Roxanne E

    2017-03-01

    The use of polymeric crosslinkers is an attractive method to modify the mechanical properties of supramolecular materials, but their effects on the self-assembly of the underlying supramolecular polymer networks are poorly understood. Modulation of the gelation pathway of a reaction-coupled low molecular weight hydrogelator is demonstrated using (bio)polymeric crosslinkers of disparate physicochemical identities, providing a handle for control over materials properties.

  13. Effects of low molecular weight chitosan (LMC-1) on shrimp preservation

    NASA Astrophysics Data System (ADS)

    Yu, Guang-Li; Wang, Yuan-Hong; Liu, Shu-Qing; Tian, Xue-Lin

    1996-06-01

    This study on the effects of low molecular weight chitosan (LMC-1) and shrimp preserving agents such as phytic acid (PA), sodium bisulfite (SB), and crustacean preservative (CP) on the preservation of shrimp ( Trachypenaeus curvirostris) and the bacteriostasis of LMC-1 showed that: (1) Different LMC-1 concentration has different bacteriostasis on E. coli, B. subtilis and S. aureau; (2) LMC-1 and CP are better than PA and SB for preserving the freshness of shrimp stored at 4 °C.

  14. Low molecular weight Neutral Boron Dipyrromethene (Bodipy) dyads for fluorescence-based neural imaging

    NASA Astrophysics Data System (ADS)

    Bai, Dan; Benniston, Andrew C.; Clift, Sophie; Baisch, Ulrich; Steyn, Jannetta; Everitt, Nicola; Andras, Peter

    2014-05-01

    The neutral low molecular weight julolidine-based borondipyrromethene (Bodipy) dyads JULBD and MJULBD were used for fast voltage-sensitive dye imaging of neurons in the crab stomatogastric ganglion. The fluorescence modulation of the dyads mirrors alterations in the membrane potential of the imaged neurons. The toxicity of the dyes towards the neurons is related to their structure in that methyl groups at the 3,5 positions results in reduced toxic effects.

  15. Inhibitors

    MedlinePlus

    ... Mutation Project (CHAMP) mutation list: a new online resource. Human Mutation. 2012; E2382-E2392. Li T, Miller CH, Payne AB, Hooper CW. The CDC Hemophilia B mutation project mutation list: a new online resource. Molecular Genetics and Genomic Medicine. 2013; 1(4): ...

  16. Molecular dynamic and docking interaction study of Heterodera glycines serine proteinase with Vigna mungo proteinase inhibitor.

    PubMed

    Prasad, C V S Siva; Gupta, Saurabh; Gaponenko, Alex; Tiwari, Murlidhar

    2013-08-01

    Many plants do produce various defense proteins like proteinase inhibitors (PIs) to protect them against various pests. PIs function as pseudosubstrates of digestive proteinase, which inhibits proteolysis in pests and leads to amino acid deficiency-based mortality. This work reports the structural interaction studies of serine proteinase of Heterodera glycines (SPHG) with Vigna mungo proteinase inhibitor (VMPI). 3D protein structure modeling, validation of SPHG and VMPI, and their putative protein-protein binding sites were predicted. Protein-protein docking followed by molecular dynamic simulation was performed to find the reliable confirmation of SPHG-VMPI complex. Trajectory analysis of each successive conformation concludes better interaction of first loop in comparison with second loop. Lysine residues of first loop were actively participating in complex formation. Overall, this study discloses the structural aspects and interaction mechanisms of VMPI with SPHG, and it would be helpful in the development of pest-resistant genetically modified crops.

  17. Molecular mutagenesis of ppGpp: turning a RelA activator into an inhibitor

    PubMed Central

    Beljantseva, Jelena; Kudrin, Pavel; Jimmy, Steffi; Ehn, Marcel; Pohl, Radek; Varik, Vallo; Tozawa, Yuzuru; Shingler, Victoria; Tenson, Tanel; Rejman, Dominik; Hauryliuk, Vasili

    2017-01-01

    The alarmone nucleotide (p)ppGpp is a key regulator of bacterial metabolism, growth, stress tolerance and virulence, making (p)ppGpp-mediated signaling a promising target for development of antibacterials. Although ppGpp itself is an activator of the ribosome-associated ppGpp synthetase RelA, several ppGpp mimics have been developed as RelA inhibitors. However promising, the currently available ppGpp mimics are relatively inefficient, with IC50 in the sub-mM range. In an attempt to identify a potent and specific inhibitor of RelA capable of abrogating (p)ppGpp production in live bacterial cells, we have tested a targeted nucleotide library using a biochemical test system comprised of purified Escherichia coli components. While none of the compounds fulfilled this aim, the screen has yielded several potentially useful molecular tools for biochemical and structural work. PMID:28157202

  18. Comparative molecular field analysis (CoMFA) of phthalazine derivatives as phosphodiesterase IV inhibitors.

    PubMed

    Chakraborti, Asit K; Gopalakrishnan, B; Sobhia, M Elizabeth; Malde, Alpeshkumar

    2003-08-04

    A comparative molecular field analysis (CoMFA) of phthalazine class of phosphodiesterase IV (PDE IV) inhibitors has been performed to correlate their chemical structures with their observed biological activity. A statistically valid model with good correlative and predictive power is reported. The leave one out cross-validation study gave cross-validation r(2)(cv) of value 0.507 at six optimum components and conventional r(2) of value 0.98. The predictive ability of the model was tested by predicting the seven molecules belonging to the test set giving predictive correlation coefficient of 0.59. This model is potentially helpful in the design of novel and more potent PDE IV inhibitors.

  19. Synthesis, biological evaluation and molecular modeling studies on novel quinonoid inhibitors of CDC25 phosphatases.

    PubMed

    Evain-Bana, Emilie; Schiavo, Lucie; Bour, Christophe; Lanfranchi, Don Antoine; Berardozzi, Simone; Ghirga, Francesca; Bagrel, Denyse; Botta, Bruno; Hanquet, Gilles; Mori, Mattia

    2017-12-01

    The cell division cycle 25 phosphatases (CDC25A, B, and C; E.C. 3.1.3.48) are key regulator of the cell cycle in human cells. Their aberrant expression has been associated with the insurgence and development of various types of cancer, and with a poor clinical prognosis. Therefore, CDC25 phosphatases are a valuable target for the development of small molecule inhibitors of therapeutic relevance. Here, we used an integrated strategy mixing organic chemistry with biological investigation and molecular modeling to study novel quinonoid derivatives as CDC25 inhibitors. The most promising molecules proved to inhibit CDC25 isoforms at single digit micromolar concentration, becoming valuable tools in chemical biology investigations and profitable leads for further optimization. [Formula: see text].

  20. The Effect of Molecular Weight on the Composite Properties of Cured Phenylethynyl Terminated Imide Oligomers

    NASA Technical Reports Server (NTRS)

    Smith, J. G., Jr.; Connell, J. W.; Hergenrother, P. M.

    1997-01-01

    As part of a program to develop high temperature/high performance structural resins for aeronautical applications, imide oligomers containing terminal phenylethynyl groups with calculated number average molecular weights of 1250, 2500 and 5000 g/mol were prepared, characterized, and evaluated as adhesives and composite matrix resins. The goal of this work was to develop resin systems that are processable using conventional processing equipment into void free composites that exhibit high mechanical properties with long term high temperature durability, and are not affected by exposure to common aircraft fluids. The imide oligomers containing terminal phenylethynyl groups were fabricated into titanium adhesive specimens and IM-7 carbon fiber laminates under 0.1 - 1.4 MPa for 1 hr at 350-371 C. The lower molecular weight oligomers exhibited higher cured Tg, better processability, and better retention of mechanical properties at elevated temperature without significantly sacrificing toughness or damage tolerance than the higher molecular weight oligomer. The neat resin, adhesive and composite properties of the cured polymers will be presented.

  1. Methanol-induced chain termination in poly(3-hydroxybutyrate) biopolymers: molecular weight control.

    PubMed

    Ashby, Richard D; Solaiman, Daniel K Y; Strahan, Gary D; Levine, Alex C; Nomura, Christopher T

    2015-03-01

    A systematic study was performed to demonstrate the impact of methanol (MeOH) on poly(3-hydroxybutyrate) (PHB) synthesis and molecular weight (MW). Glycerine was used as the primary carbon source with varying concentrations of MeOH. Methanol retarded but did not completely inhibit growth and PHB production in Pseudomonas oleovorans. Proton NMR analysis revealed that the PHB polymers were end-capped with methoxy chemical groups causing MW reductions. The MW decreases were contingent upon the initial MeOH media concentration and the duration of the fermentations. The largest impact occurred at an initial MeOH concentration of 0.10% (w/v) where the number average molecular weights (Mn) decreased by 39%, 55%, and 72% in the 48, 72 and 96 h cultures, respectively. Diffusion ordered NMR spectroscopy revealed a diffusivity (D) increase in the smaller molecular weight polymers with the PHB synthesized in the presence of 0.85% MeOH (72 h post-inoculation) having a D value of 0.66×10(-10) m2/s. Diffusivity increases indicate a reduction in hydrodynamic radii (Rhz) consistent with shorter chain-lengths. Crude glycerine from the biodiesel production process has been used as an inexpensive fermentation feedstock for polyhydroxyalkanoate (PHA) synthesis but its composition is facility-dependent. This information will be vital to tailor PHA properties to specific applications.

  2. Phosphorylation of low-molecular-weight proteins in preparations of rat heart sarcolemma and sarcoplasmic reticulum.

    PubMed

    Lamers, J M; Stinis, J T

    1982-01-01

    Two substrate proteins for cAMP-dependent protein kinase detected in a rat heart sarcolemma preparation displayed molecular weights of 24,000 and 9000 in sodium dodecyl sulfate gels and were shown to be interconvertible. The 9000-dalton protein could readily be separated from other low molecular weight phosphoproteins (mol. wt. 14,000 and 7000) by the use of 15% polyacrylamide gels. In addition to an endogenous cAMP-dependent protein kinase the membrane preparation also contained a protein-phosphorylation system that required Ca2+ and calmodulin. It appeared that both 24,000- and 55,000-dalton proteins were substrates for the endogenous Ca2+- and calmodulin-dependent protein kinase. Contaminating sarcoplasmic reticulum vesicles, first loaded with calcium oxalate, could be separated from the enriched sarcolemma preparation by sucrose gradient centrifugation. The separation was confirmed by comparative analysis of 5'-nucleotidase, Na+ -Ca2+ antiporter, and (Ca2+ + Mg2+)-dependent ATPase activities and by determination of gel electrophoretic (phospho)protein composition, sialic acid, cholesterol, and phospholipid contents. The 24,000-dalton phosphoprotein complex was equally distributed between sarcolemmal and sarcoplasmic reticulum fractions, whereas the 55,000- and 7000-dalton proteins were predominantly found in the sarcolemmal fraction. The 24,000-dalton protein was most likely phospholamban, because no other phosphoprotein was found in the 20,000 molecular weight range.

  3. Determination of dextrose equivalent value and number average molecular weight of maltodextrin by osmometry.

    PubMed

    Rong, Y; Sillick, M; Gregson, C M

    2009-01-01

    Dextrose equivalent (DE) value is the most common parameter used to characterize the molecular weight of maltodextrins. Its theoretical value is inversely proportional to number average molecular weight (M(n)), providing a theoretical basis for correlations with physical properties important to food manufacturing, such as: hygroscopicity, the glass transition temperature, and colligative properties. The use of freezing point osmometry to measure DE and M(n) was assessed. Measurements were made on a homologous series of malto-oligomers as well as a variety of commercially available maltodextrin products with DE values ranging from 5 to 18. Results on malto-oligomer samples confirmed that freezing point osmometry provided a linear response with number average molecular weight. However, noncarbohydrate species in some commercial maltodextrin products were found to be in high enough concentration to interfere appreciably with DE measurement. Energy dispersive spectroscopy showed that sodium and chloride were the major ions present in most commercial samples. Osmolality was successfully corrected using conductivity measurements to estimate ion concentrations. The conductivity correction factor appeared to be dependent on the concentration of maltodextrin. Equations were developed to calculate corrected values of DE and M(n) based on measurements of osmolality, conductivity, and maltodextrin concentration. This study builds upon previously reported results through the identification of the major interfering ions and provides an osmolality correction factor that successfully accounts for the influence of maltodextrin concentration on the conductivity measurement. The resulting technique was found to be rapid, robust, and required no reagents.

  4. Efficient bulk heterojunction photovoltaic cells using small-molecular-weight organic thin films.

    PubMed

    Peumans, Peter; Uchida, Soichi; Forrest, Stephen R

    2003-09-11

    The power conversion efficiency of small-molecular-weight and polymer organic photovoltaic cells has increased steadily over the past decade. This progress is chiefly attributable to the introduction of the donor-acceptor heterojunction that functions as a dissociation site for the strongly bound photogenerated excitons. Further progress was realized in polymer devices through use of blends of the donor and acceptor materials: phase separation during spin-coating leads to a bulk heterojunction that removes the exciton diffusion bottleneck by creating an interpenetrating network of the donor and acceptor materials. The realization of bulk heterojunctions using mixtures of vacuum-deposited small-molecular-weight materials has, on the other hand, posed elusive: phase separation induced by elevating the substrate temperature inevitably leads to a significant roughening of the film surface and to short-circuited devices. Here, we demonstrate that the use of a metal cap to confine the organic materials during annealing prevents the formation of a rough surface morphology while allowing for the formation of an interpenetrating donor-acceptor network. This method results in a power conversion efficiency 50 per cent higher than the best values reported for comparable bilayer devices, suggesting that this strained annealing process could allow for the formation of low-cost and high-efficiency thin film organic solar cells based on vacuum-deposited small-molecular-weight organic materials.

  5. Synthesis of High-Molecular-Weight Polyhydroxyalkanoates by Marine Photosynthetic Purple Bacteria

    PubMed Central

    Higuchi-Takeuchi, Mieko; Morisaki, Kumiko; Toyooka, Kiminori; Numata, Keiji

    2016-01-01

    Polyhydroxyalkanoate (PHA) is a biopolyester/bioplastic that is produced by a variety of microorganisms to store carbon and increase reducing redox potential. Photosynthetic bacteria convert carbon dioxide into organic compounds using light energy and are known to accumulate PHA. We analyzed PHAs synthesized by 3 purple sulfur bacteria and 9 purple non-sulfur bacteria strains. These 12 purple bacteria were cultured in nitrogen-limited medium containing acetate and/or sodium bicarbonate as carbon sources. PHA production in the purple sulfur bacteria was induced by nitrogen-limited conditions. Purple non-sulfur bacteria accumulated PHA even under normal growth conditions, and PHA production in 3 strains was enhanced by nitrogen-limited conditions. Gel permeation chromatography analysis revealed that 5 photosynthetic purple bacteria synthesized high-molecular-weight PHAs, which are useful for industrial applications. Quantitative reverse transcription polymerase chain reaction analysis revealed that mRNA levels of phaC and PhaZ genes were low under nitrogen-limited conditions, resulting in production of high-molecular-weight PHAs. We conclude that all 12 tested strains are able to synthesize PHA to some degree, and we identify 5 photosynthetic purple bacteria that accumulate high-molecular-weight PHA molecules. Furthermore, the photosynthetic purple bacteria synthesized PHA when they were cultured in seawater supplemented with acetate. The photosynthetic purple bacteria strains characterized in this study should be useful as host microorganisms for large-scale PHA production utilizing abundant marine resources and carbon dioxide. PMID:27513570

  6. Isolation and characterization of low molecular weight glycosaminoglycans from marine mollusc Amussium pleuronectus (linne) using chromatography.

    PubMed

    Saravanan, R; Shanmugam, A

    2010-03-01

    The glycosaminoglycan (GAG) heparin is a polyanionic sulfated polysaccharide most recognized for its anticoagulant activity. In the present study, the GAGs were extracted from bivalve mollusc Amussium pleuronectus. The crude GAGs were fractionated by ion-exchange (DEAE-cellulose and Amberlite IRA-900 & 120) chromatography. The recovered active fractions (as determined by metachromatic assay) were confirmed by agarose gel electrophoresis and the active fractions were purified in Sephadex G-100 column. Fractionated and purified GAG molecular weight was determined through gradient polyacrylamide gel electrophoresis. The structural characterization of low molecular weight GAG was analyzed by Fourier transform infrared spectroscopy. The activated partial thromboplastin time of purified GAG is 95 IU/mg and has molecular weight 6,500-7,500 Da. The disaccharide compositional analysis on the GAG sample was sulfated like porcine intestinal mucosal heparan sulfate, and it contains equivalent amount of uronic acid and hexosamine. The results of this study suggest that the GAG from A. pleuronectus could be an alternative source of heparin.

  7. Systematic Analysis of Polymer Molecular Weight Influence on the Organic Photovoltaic Performance.

    PubMed

    Katsouras, Athanasios; Gasparini, Nicola; Koulogiannis, Chrysanthos; Spanos, Michael; Ameri, Tayebeh; Brabec, Christoph J; Chochos, Christos L; Avgeropoulos, Apostolos

    2015-10-01

    The molecular weight of an electron donor-conjugated polymer is as essential as other well-known parameters in the chemical structure of the polymer, such as length and the nature of any side groups (alkyl chains) positioned on the polymeric backbone, as well as their placement, relative strength, the ratio of the donor and acceptor moieties in the backbone of donor-acceptor (D-A)-conjugated polymers, and the arrangement of their energy levels for organic photovoltaic performance. Finding the "optimal" molecular weight for a specific conjugated polymer is an important aspect for the development of novel photovoltaic polymers. Therefore, it is evident that the chemistry of functional conjugated polymers faces major challenges and materials have to adopt a broad range of specifications in order to be established for high photovoltaic performance. In this review, the approaches followed for enhancing the molecular weight of electron-donor polymers are presented in detail, as well as how this influences the optoelectronic properties, charge transport properties, structural conformation, morphology, and the photovoltaic performance of the active layer.

  8. Synthesis of High-Molecular-Weight Polyhydroxyalkanoates by Marine Photosynthetic Purple Bacteria.

    PubMed

    Higuchi-Takeuchi, Mieko; Morisaki, Kumiko; Toyooka, Kiminori; Numata, Keiji

    2016-01-01

    Polyhydroxyalkanoate (PHA) is a biopolyester/bioplastic that is produced by a variety of microorganisms to store carbon and increase reducing redox potential. Photosynthetic bacteria convert carbon dioxide into organic compounds using light energy and are known to accumulate PHA. We analyzed PHAs synthesized by 3 purple sulfur bacteria and 9 purple non-sulfur bacteria strains. These 12 purple bacteria were cultured in nitrogen-limited medium containing acetate and/or sodium bicarbonate as carbon sources. PHA production in the purple sulfur bacteria was induced by nitrogen-limited conditions. Purple non-sulfur bacteria accumulated PHA even under normal growth conditions, and PHA production in 3 strains was enhanced by nitrogen-limited conditions. Gel permeation chromatography analysis revealed that 5 photosynthetic purple bacteria synthesized high-molecular-weight PHAs, which are useful for industrial applications. Quantitative reverse transcription polymerase chain reaction analysis revealed that mRNA levels of phaC and PhaZ genes were low under nitrogen-limited conditions, resulting in production of high-molecular-weight PHAs. We conclude that all 12 tested strains are able to synthesize PHA to some degree, and we identify 5 photosynthetic purple bacteria that accumulate high-molecular-weight PHA molecules. Furthermore, the photosynthetic purple bacteria synthesized PHA when they were cultured in seawater supplemented with acetate. The photosynthetic purple bacteria strains characterized in this study should be useful as host microorganisms for large-scale PHA production utilizing abundant marine resources and carbon dioxide.

  9. Molecular weight-dependent genetic information transfer with disulfide-linked polyethylenimine-based nonviral vectors.

    PubMed

    Parhiz, Hamideh; Hashemi, Maryam; Hatefi, Arash; Shier, Wayne Thomas; Farzad, Sara Amel; Ramezani, Mohammad

    2013-07-01

    One strategy for improving gene vector properties of polyethylenimine is to facilitate individual transfection mechanism steps. This study investigates (i) improving transfection efficiency by attaching peptide nuclear localization signals (nuclear localization signals: SV40 large T antigen nuclear localization signal or C-terminus of histone H1) to polyethylenimine (10 kDa) and (ii) using disulfide linkages, which are expected to be stable during polyplex formation, but cleaved inside cells giving improved gene release. Nuclear localization signal-containing polyplexes exhibited low cytotoxicity, whereas transfection efficiency with high molecular weight plasmid DNA increased up to 3.6 times that of underivatized polyethylenimine in Neuro2A cells at higher molar ratio of polyethylenimine-nitrogen to DNA-phosphate (N/P) ratios. However, with luciferase-specific low molecular weight small interfering RNA in Neuro2A/EGFPLuc cells, nuclear localization signal-containing polyplexes with disulfide linkages caused substantial cytotoxicity at N/P ratios >15 and no consistent significant reduction in luciferase expression. Possible explanations for molecular weight-dependent differences in genetic information transfer by polyplexes containing disulfide-linked nuclear localization signals are discussed.

  10. Melt rheology and molecular weight degradation of amylopectin during multiple pass extrusion of starch

    SciTech Connect

    Willett, J.L.; Millard, M.M.; Jasberg, B.K.

    1996-12-31

    The degradation of starch during extrusion and the role of specific mechanical energy (SME) in this process have been widely studied for single pass extrusion, Multiple extrusion histories are not uncommon in the plastics industry, but little if any has been reported on their effects on starch. Native waxy maize starch (app. 98% amylopectin) was initially converted to a thermoplastic by twin screw extrusion. This extrudate was equilibrated to either 18% or 23% moisture content, and subsequently re-extruded in a single screw extruder (3:1 compression screw) at 110{degrees}C or 130{degrees}C. Melt viscosity data were calculated using the output-pressure data from the second pass. The melts exhibited shear thinning behavior; the power law index increased with temperature, and slightly with moisture content. Molecular weights of selected second-pass extrudates, as well as the native starch and the first-pass extrudate, were measured by light scattering in dimethyl sulfoxide/water. The initial extrusion pass reduced the molecular weight from 300 million to 50 million. Molecular weight reductions in the second pass increased with increasing SME. A first order expression was shown to fit the MW-SME data with a correlation coefficient of 0.91. Implications of the degradation on extrusion processing of starch and the use of single screw extruders for rheological characterization will be discussed.

  11. Influence of molecular weight on in vitro immunostimulatory properties of instant coffee.

    PubMed

    Passos, Cláudia P; Cepeda, Márcio R; Ferreira, Sónia S; Nunes, Fernando M; Evtuguin, Dmitry V; Madureira, Pedro; Vilanova, Manuel; Coimbra, Manuel A

    2014-10-15

    Instant coffee was prepared and fractionated into higher (>100kDa), medium (5-10, 10-30, 30-100kDa) and lower (1-5, <1kDa) molecular weight fractions. Sugars and linkage composition characteristics of arabinogalactans and galactomannans were recovered in all fractions. Also, amino acid analysis performed after hydrolysis showed similar compositions in all fractions. On the contrary, free chlorogenic acids and caffeine were only detected in the lowest molecular weight fraction (<1kDa). A direct relationship between the melanoidins browning index and the molecular weight was observed. The fractions obtained were incubated in vitro with murine spleen lymphocytes in order to evaluate their possible immunostimulatory abilities. The surface expression of CD69 (early activation marker) on different lymphocyte sub-populations showed that the fraction with 1-5kDa was able to induce activation of B-lymphocytes. This was the only fraction to induce B-lymphocyte activation, since all the other fractions failed, even when higher concentrations were used.

  12. Molecular weight distribution of phosphorus fraction of aquatic dissolved organic matter.

    PubMed

    Ged, Evan C; Boyer, Treavor H

    2013-05-01

    This study characterized dissolved organic phosphorus (DOP) that is discharged from the Everglades Agricultural Area as part of the larger pool of aquatic dissolved organic matter (DOM). Whole water samples collected at the Everglades stormwater treat area 1 West (STA-1 W) were fractionated using a batch ultrafiltration method to separate organic compounds based on apparent molecular weight (AMW). Each AMW fraction of DOM was characterized for phosphorus, carbon, nitrogen, UV absorbance, and fluorescence. The DOP content of the Everglades water matrix was characteristically variable constituting 4-56% of total phosphorus (TP) and demonstrated no correlation with dissolved organic carbon (DOC). Measured values for DOP exceeded 14μgL(-1) in four out of five sampling dates making phosphorus load reductions problematic for the stormwater treatment areas (STAs), which target inorganic phosphorus and have a goal of 10μgL(-1) as TP. The molecular weight distributions revealed 40% of DOP is high molecular weight, aromatic-rich DOM. The results of this research are expected to be of interest to environmental chemists, environmental engineers, and water resources managers because DOP presents a major obstacle to achieving TP levels <10μgL(-1).

  13. Ferrous iron chelating property of low-molecular weight succinoglycans isolated from Sinorhizobium meliloti.

    PubMed

    Cho, Eunae; Choi, Jae Min; Kim, Hwanhee; Tahir, Muhammad Nazir; Choi, Youngjin; Jung, Seunho

    2013-04-01

    Iron is an essential nutrient for nitrogen-fixing legume root nodules, and the chelation of ferrous iron plays an important role in the mobility and availability of iron to the legume. In the present study, we investigated the iron-binding properties of low-molecular weight succinoglycans isolated from the nitrogen-fixing bacterium, Sinorhizobium meliloti. The low-molecular weight succinoglycans comprising three monomers (M1-M3), four dimers (D1-D4), and six trimers (T1-T6) of the succinoglycan repeating unit were purified by various chromatographic techniques. Interestingly, the colorimetric ferrozine method showed that the succinoglycans T6, M3, and D3 demonstrated a ferrous iron chelating ability of 83, 63, and 38 % per mg, respectively. The individual binding constants were determined as 43703, 2313, and 760 M(-1) for succinoglycans T6, M3, and D3 using ultraviolet-visible spectroscopy. The complexation of succinoglycan and ferrous iron can cause structural changes, which were analyzed by circular dichroism spectroscopy. Furthermore, the complex could provide antioxidant activity through an anti-Fenton reaction. These results demonstrate that the low-molecular weight succinoglycans can effectively modulate iron biochemistry as a novel ferrous iron-acquisition system of S. meliloti.

  14. Analysis of low molecular weight compounds by MALDI-FTICR-MS.

    PubMed

    Wang, Hao-Yang; Chu, Xu; Zhao, Zhi-Xiong; He, Xiao-Shuang; Guo, Yin-Long

    2011-05-15

    This review focuses on recent applications of matrix-assisted laser desorption ionization-Fourier-transform ion cyclotron resonance mass spectrometry (MALDI-FTICR-MS) in qualitative and quantitative analysis of low molecular weight compounds. The scope of the work includes amino acids, small peptides, mono and oligosaccharides, lipids, metabolic compounds, small molecule phytochemicals from medicinal herbs and even the volatile organic compounds from tobacco. We discuss both direct analysis and analysis following derivatization. In addition we review sample preparation strategies to reduce interferences in the low m/z range and to improve sensitivities by derivatization with charge tags. We also present coupling of head space techniques with MALDI-FTICR-MS. Furthermore, omics analyses based on MALDI-FTICR-MS were also discussed, including proteomics, metabolomics and lipidomics, as well as the relative MS imaging for bio-active low molecular weight compounds. Finally, we discussed the investigations on dissociation/rearrangement processes of low molecular weight compounds by MALDI-FTICR-MS.

  15. Megalin Knockout Mice as an Animal Model of Low Molecular Weight Proteinuria

    PubMed Central

    Leheste, Jörg-Robert; Rolinski, Boris; Vorum, Henrik; Hilpert, Jan; Nykjaer, Anders; Jacobsen, Christian; Aucouturier, Pierre; Moskaug, Jan Øivind; Otto, Albrecht; Christensen, Erik Ilsø; Willnow, Thomas E.

    1999-01-01

    Megalin is an endocytic receptor expressed on the luminal surface of the renal proximal tubules. The receptor is believed to play an important role in the tubular uptake of macromolecules filtered through the glomerulus. To elucidate the role of megalin in vivo and to identify its endogenous ligands, we analyzed the proximal tubular function in mice genetically deficient for the receptor. We demonstrate that megalin-deficient mice exhibit a tubular resorption deficiency and excrete low molecular weight plasma proteins in the urine (low molecular weight proteinuria). Proteins excreted include small plasma proteins that carry lipophilic compounds including vitamin D-binding protein, retinol-binding protein, α1-microglobulin and odorant-binding protein. Megalin binds these proteins and mediates their cellular uptake. Urinary loss of carrier proteins in megalin-deficient mice results in concomitant loss of lipophilic vitamins bound to the carriers. Similar to megalin knockout mice, patients with low molecular weight proteinuria as in Fanconi syndrome are also shown to excrete vitamin/carrier complexes. Thus, these results identify a crucial role of the proximal tubule in retrieval of filtered vitamin/carrier complexes and the central role played by megalin in this process. PMID:10514418

  16. Graphene Nanocomposites with High Molecular Weight Poly(ε-caprolactone) Grafts: Controlled Synthesis and Accelerated Crystallization

    DOE PAGES

    Mondal, Titash; Ashkar, Rana; Butler, Paul; ...

    2016-02-08

    Grafting of high molecular weight polymers to graphitic nanoplatelets is a critical step toward the development of high performance graphene nanocomposites. However, designing such a grafting route has remained a major impediment. Herein, we report a "grafting to" synthetic pathway by which high molecular weight polymer, poly(e-caprolactone) (PCL), is tethered, at high grafting density, to highly anisotropic graphitic nanoplatelets. The efficacy of this tethering route and the resultant structural arrangements within the composite are confirmed by neutron and X-ray scattering measurements in the melt and solution phase. In the semicrystalline state, Xray analysis indicates that chain tethering onto the graphiticmore » nanoplatelets results in conformational changes of the polymer chains, which enhance the nucleation process and aid formation of PCL crystallites. This is corroborated by the superior thermal properties of the composite, manifested in accelerated crystallization kinetics and a significant increase in the thermal degradation temperature. Lastly, in principle, this synthesis route can be extended to a variety of high molecular weight polymers, which can open new avenues to solution-based processing of graphitic nanomaterials and the fabrication of complex 3D patterned graphitic nanocomposites.« less

  17. Graphene Nanocomposites with High Molecular Weight Poly(ε-caprolactone) Grafts: Controlled Synthesis and Accelerated Crystallization

    SciTech Connect

    Mondal, Titash; Ashkar, Rana; Butler, Paul; Bhowmick, Anil K.; Krishnamoorti, Ramanan

    2016-02-08

    Grafting of high molecular weight polymers to graphitic nanoplatelets is a critical step toward the development of high performance graphene nanocomposites. However, designing such a grafting route has remained a major impediment. Herein, we report a "grafting to" synthetic pathway by which high molecular weight polymer, poly(e-caprolactone) (PCL), is tethered, at high grafting density, to highly anisotropic graphitic nanoplatelets. The efficacy of this tethering route and the resultant structural arrangements within the composite are confirmed by neutron and X-ray scattering measurements in the melt and solution phase. In the semicrystalline state, Xray analysis indicates that chain tethering onto the graphitic nanoplatelets results in conformational changes of the polymer chains, which enhance the nucleation process and aid formation of PCL crystallites. This is corroborated by the superior thermal properties of the composite, manifested in accelerated crystallization kinetics and a significant increase in the thermal degradation temperature. Lastly, in principle, this synthesis route can be extended to a variety of high molecular weight polymers, which can open new avenues to solution-based processing of graphitic nanomaterials and the fabrication of complex 3D patterned graphitic nanocomposites.

  18. Study of Low Molecular Weight Impurities in Pluronic Triblock Copolymers using MALDI, Interaction Chromatography, and NMR

    NASA Astrophysics Data System (ADS)

    Helming, Z.; Zagorevski, D.; Ryu, C. Y.

    2014-03-01

    Poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers are a group of commercial macromolecular amphiphilic surfactants that have been widely studied for their applications in polymer-based nanotechnology and drug-delivery. It has been well-established that the synthesis of commercial Pluronic triblocks results in low molecular weight ``impurities,'' which are generally disregarded in the applications and study of these polymers. These species have been shown to have significant effects on the rheological properties of the material, as well as altering the supramolecular ``micellar'' structures for which the polymers are most often used. We have isolated the impurities from the bulk Pluronic triblock using Interaction Chromatography (IC) techniques, and subjected them to analysis by H1 NMR and MALDI (Matrix-Assisted Laser Desorption Ionization) Mass Spectrometry to identify relative block composition and molecular weight information. We report significant evidence of at least two polymeric components: a low-molecular-weight homopolymer of poly(ethylene oxide) and a ``blocky'' copolymer of both poly(ethylene oxide) and poly(propylene oxide). This has significant implications, not only for the applied usage of Pluronic triblock copolymers, but for the general scientific acceptance of the impurities and their effects on Pluronic micelle and hydrogel formation.

  19. Low molecular weight DNA replication intermediates in Escherichia coli: mechanism of formation and strand specificity

    PubMed Central

    Amado, Luciana; Kuzminov, Andrei

    2013-01-01

    Chromosomal DNA replication intermediates, revealed in ligase-deficient conditions in vivo, are of low molecular weight independently of the organism, suggesting discontinuous replication of both the leading and the lagging DNA strands. Yet, in vitro experiments with purified enzymes replicating sigma-structured substrates show continuous synthesis of the leading DNA strand in complete absence of ligase, supporting the textbook model of semi-discontinuous DNA replication. The discrepancy between the in vivo and in vitro results is rationalized by proposing that various excision repair events nick continuously-synthesized leading strands after synthesis, producing the observed low molecular weight intermediates. Here we show that, in an E. coli ligase-deficient strain with all known excision repair pathways inactivated, new DNA is still synthesized discontinuously. Furthermore, hybridization to strand-specific targets demonstrates that the low molecular weight replication intermediates come from both the lagging and the leading strands. These results support the model of discontinuous leading strand synthesis in E. coli. PMID:23876705

  20. Detonation-Synthesis Nanodiamonds in Compositions of Ultrahigh-Molecular-Weight Polyethylene

    NASA Astrophysics Data System (ADS)

    Dubkova, V. I.; Korzhenevskii, A. P.; Krut‧ko, N. P.; Komarevich, V. G.; Kul‧bistkaya, L. V.

    2016-07-01

    A study has been made of the influence of an ultradisperse carbonaceous product, i.e., detonation-synthesis nanodiamonds, on the structure and properties of nanocomposites based on ultrahigh-molecular-weight polyethylene using electron microscopy and acoustic, electrophysical, thermomechanical, and x-ray phase analysis methods It has been shown that a diamond blend is a structurally active filler of ultrahigh-molecular-weight polyethylene, which changes the crystalline and supermolecular structure of the polymer during its melt crystallization under the conditions of uniaxial plastic deformation. The developed polymer nanocomposites based on ultrahigh-molecular-weight polyethylene, which contain 0.5-0.25 wt.% of the diamond blend, possess higher than average indices of hardness, modulus of elasticity, and electrical conductivity manifested to a larger extent in the frequency range 1-10 kHz, a low friction factor (0.15-0.18), and high resistance to wear under dry-friction conditions (the wear rate is 10-4-10-5 mg/m).

  1. Properties and Microstructural Characteristic of Kaolin Geopolymer Ceramics with Addition of Ultra High Molecular Weight Polyethylene

    NASA Astrophysics Data System (ADS)

    Ahmad, Romisuhani; Bakri Abdullah, Mohd Mustafa Al; Hussin, Kamarudin; Sandu, Andrei Victor; Binhussain, Mohammed; Ain Jaya, Nur

    2016-06-01

    In this paper, the mechanical properties and microstructure of kaolin geopolymer ceramics with addition of Ultra High Molecular Weight Polyethylene were studied. Inorganic polymers based on alumina and silica polysialate units were synthesized at room temperature from kaolin and sodium silicate in a highly alkaline medium, followed by curing and drying at 80 °C. Alkaline activator was formed by mixing the 12 M NaOH solution with sodium silicate at a ratio of 0.24. Addition of Ultra High Molecular Weight Polyethylene to the kaolin geopolymer are fabricated with Ultra High Molecular Weight Polyethylene content of 2, 4, 6 and 8 (wt. %) by using powder metallurgy method. The samples were heated at 1200 °C and the strength and morphological were tested. It was found that the flexural strength for the kaolin geopolymer ceramics with addition of UHMWPE were improved and generally increased with the increasing of UHMWPE loading. The result revealed that the optimum flexural strength was obtained at UHMWPE loading of 4 wt. % (92.1 MPa) and the flexural strength started to decrease. Microstructural analysis showed the samples appeared to have more number of pores and connected of pores increased with the increasing of UHMWPE content.

  2. Molecular weight recognition in the multiple-stranded helix of a synthetic polymer without specific monomer-monomer interaction.

    PubMed

    Kumaki, Jiro; Kawauchi, Takehiro; Ute, Koichi; Kitayama, Tatsuki; Yashima, Eiji

    2008-05-21

    Stereoregular isotactic and syndiotactic poly(methyl methacrylate)s (it- and st-PMMAs) are known to form a multiple-stranded complementary helix, so-called stereocomplex (SC) through van der Waals interactions, which is a rare example of helical supramolecular structures formed by a commodity polymer. In this study, we prepared SCs by using uniform it- and st-PMMAs and those with a narrow molecular weight distribution having different molecular weights and investigated their structures in detail using high-resolution atomic force microscopy as a function of the molecular weight and molecular weight distribution of the component PMMAs. We found that complementary it- and st-PMMAs with the longer molecular length determine the total length of the SC, and molecules of the shorter component associate until they fill up or cover the longer component. These observations support a supramolecular triple-stranded helical structure of the SCs composed of a double-stranded helix of two intertwined it-PMMA chains included in a single helix of st-PMMA, and this triple-stranded helix model of the SCs appears to be applicable to the it- and st-PMMAs having a wide range of molecular weights we employed in this study. In homogeneous double-stranded helices of it-PMMA, it has been found that, in mixtures of two it-PMMAs with different molecular weights, chains of the same molecular weight selectively form a double-stranded it-PMMA helix, or recognize the molecular weights of each other ("molecular sorting"). We thus demonstrate that molecular weight recognition is possible, without any specific interaction between monomer units, through the formation of a topological multiple-stranded helical structure based upon van der Waals interaction.

  3. Screening the low molecular weight fraction of human serum using ATR-IR spectroscopy.

    PubMed

    Bonnier, Franck; Brachet, Guillaume; Duong, Romain; Sojinrin, Tobiloba; Respaud, Renaud; Aubrey, Nicolas; Baker, Matthew J; Byrne, Hugh J; Chourpa, Igor

    2016-10-01

    Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. Spectroscopic detection of potential serum biomarkers present at relatively low concentrations can be improved using pre-analytical depletion of the HMWF. In the present study, human serum fractionation by centrifugal filtration was used prior to analysis by Attenuated Total Reflection infrared spectroscopy. Using a model sample based on glycine spiked serum, it is demonstrated that the screening of the LMWF can be applied to quantify blinded concentrations up to 50 times lower. Moreover, the approach is easily transferable to different bodily fluids which would support the development of more efficient and suitable clinical protocols exploring vibrational spectroscopy based ex-vivo diagnostic tools. Revealing serum LMWF for spectral serological diagnostic applications.

  4. The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering.

    PubMed

    Yang, Cuixia; Cao, Manlin; Liu, Hua; He, Yiqing; Xu, Jing; Du, Yan; Liu, Yiwen; Wang, Wenjuan; Cui, Lian; Hu, Jiajie; Gao, Feng

    2012-12-14

    CD44 is a major cell surface receptor for the glycosaminoglycan hyaluronan (HA). Native high molecular weight hyaluronan (nHA) and oligosaccharides of hyaluronan (oHA) provoke distinct biological effects upon binding to CD44. Despite the importance of such interactions, however, the feature of binding with CD44 at the cell surface and the molecular basis for functional distinction between different sizes of HA is still unclear. In this study we investigated the effects of high and low molecular weight hyaluronan on CD44 clustering. For the first time, we provided direct evidence for a strong relationship between HA size and CD44 clustering in vivo. In CD44-transfected COS-7 cells, we showed that exogenous nHA stimulated CD44 clustering, which was disrupted by oHA. Moreover, naturally expressed CD44 was distributed into clusters due to abundantly expressed nHA in HK-2 cells (human renal proximal tubule cells) and BT549 cells (human breast cancer cell line) without exogenous stimulation. Our results suggest that native HA binding to CD44 selectively induces CD44 clustering, which could be inhibited by oHA. Finally, we demonstrated that HA regulates cell adhesion in a manner specifically dependent on its size. oHA promoted cell adhesion while nHA showed no effects. Our results might elucidate a molecular- and/or cellular-based mechanism for the diverse biological activities of nHA and oHA.

  5. Mass spectrometric techniques for characterizing low-molecular-weight resins used as paint varnishes.

    PubMed

    Bonaduce, I; Colombini, M P; Degano, I; Di Girolamo, F; La Nasa, J; Modugno, F; Orsini, S

    2013-01-01

    The molecular structure of three low-molecular-weight resins used as paint varnishes has been characterized by use of an approach based on three different mass spectrometric techniques. We investigated the ketone resin MS2A, the aldehyde resin Laropal A81, and the hydrocarbon resin Regalrez 1094, now commonly used in restoration. To date, the molecular structures of these resins have not been completely elucidated. To improve current knowledge of the chemical composition of these materials, information obtained by gas chromatography-mass spectrometry (GC/MS), pyrolysis-gas chromatography-mass spectrometry (Py/GC/MS), and electrospray ionization mass spectrometry (ESI-Q-ToF) was combined. Analysis, in solution, of the whole polymeric fraction of the resins by flow-injection ESI-Q-ToF, and of the non-polymeric fraction by GC-MS, enabled us to identify previously unreported features of the polymer structures. In addition, the Py-GC/MS profiles that we obtained will help to enhance the databases currently available in the literature. The proposed approach can be extended to other low-molecular-weight resins used as varnishes in conservation.

  6. Azobenzene Containing Low-Molecular Weight Organic Glasses for Optical Recording

    NASA Astrophysics Data System (ADS)

    Aleksejeva, J.; Teteris, J.; Tokmakovs, A.

    In this work photoinduced processes and holographic surface relief formation in azobenzene containing low- molecular weight organic glasses were studied. The molecular glasses due to trans-cis isomerisation and photo- orientation of molecules possess high sensitivity to the light irradiation and therefore they are promising media for holographic recording. Electric field of linearly polarized light causes an alignment of molecule dipoles perpendicularly to the electric field vector and this process is accompanied by an appearance of photoinduced optical anisotropy in organic glasses. The photoinduced birefringence and dichroism induced by 532 nm light was studied. Holographic recording in organic molecular glasses was performed with 532 nm solid-state diode-pumped laser Verdi-6. Very rapid holographic grating recording and surface relief formation at small recording beam intensities was observed. The dependence of recorded grating diffraction efficiency and surface relief depth on recording beams polarization state and intensities was studied. The surface relief was studied with AFM.

  7. Characterization of high-molecular-weight glutenin subunits from Eremopyrum bonaepartis and identification of a novel variant with unusual high molecular weight and altered cysteine residues.

    PubMed

    Jiang, Qian-Tao; Zhang, Xiao-Wei; Ma, Jian; Wei, Long; Zhao, Shan; Zhao, Quan-Zhi; Qi, Peng-Fei; Lu, Zhen-Xiang; Zheng, You-Liang; Wei, Yu-Ming

    2014-04-01

    We characterized two high-molecular-weight glutenin subunit (HMW-GS) variants from Eremopyrum bonaepartis, determined their complete open reading frames, and further expressed them in a bacterial system. The variants have many novel structural features compared with typical subunits encoded by Glu-1 loci: 1Fx3.7 and 1Fy1.5 exhibit hybrid properties of x- and y-type subunits. In addition, unusual molecular mass and altered number and distribution of cysteine residues were unique features of HMW-GSs encoded by Glu-F1 from E. bonaepartis. The mature 1Fx3.7 subunit has a full length of 1,223 amino acid residues, making it the largest subunit found thus far, while 1Fy1.5 is just 496 residues. In addition, the mutated PGQQ repeat motif was found in the repetitive region of 1Fx3.7. Although it has a similar molecular mass to that previously reported for 1Dx2.2, 1Dx2.2* and 1S(sh)x2.9 subunits, 1Fx3.7 appears to have had a different evolutionary history. The N-terminal and repetitive regions have a total of four additional cysteine residues, giving 1Fx3.7 a total of eight cysteines, while 1Fy1.5 has only six cysteines because the GHCPTSPQQ nonapeptide at the end of the repetitive region is deleted. With its extra cysteine residues and the longest repetitive region, features that are relevant to good wheat quality, the 1Fx3.7 subunit gene could be an excellent candidate for applications in wheat quality improvement.

  8. A molecular modeling study of inhibitors of nuclear factor kappa-B (p50) DNA binding

    NASA Astrophysics Data System (ADS)

    Pande, Vineet; Sharma, Rakesh K.; Inoue, Jun-Ichiro; Otsuka, Masami; Ramos, Maria J.

    2003-12-01

    Nuclear Factor-kappa B (NF-κB) is an inducible transcription factor of the Rel family, and is sequestered in the cytoplasm by the IκB family of proteins. NF-κB can exist in several dimeric forms, but the p50/p65 heterodimer is the predominant one. Activation of NF-κB by a range of stimuli including viral products, and oxidative stress, leads to phosphorylation and proteasome dependent degradation of IκB, leading to the release of free NF-κB. This free NF-κB then binds to its target sites (κB sites in the DNA) to initiate transcription. These κB sites are also present in the Long Terminal Repeat (LTR) of HIV-1, and hence NF-κB (p50 subunit) binding to LTR-DNA is critical in viral replication. Targeting direct p50-DNA binding, in this regard, is a novel approach to design anti-HIV gene expression inhibitors, which do not have the problem of resistance unlike in other anti-HIV strategies. The present study is a part of our search for leads for the specific inhibition of p50-DNA binding. We have been experimentally studying different types of these inhibitors, and in this work, we attempted to get a common definition of their structural mechanism onto p50-DNA binding. Using three different classes of inhibitors, we modelled their association with the DNA-Binding Region (DBR) of the p50 subunit of NF-κB. Docking studies were carried out using a genetic algorithm based program (GOLD). Further, to compare electrostatic complementarity in the association of the inhibitors with the DBR, Molecular Electrostatic Potentials (MEPs) were generated for the DBR and each inhibitor. The results of docking revealed a strong network of hydrogen bonding interactions for every active inhibitor, and the contrary for the less active ones. Further, the MEPs revealed that the DBR of p50 represents a surface of electropositive potential, and the active inhibitors represent a complementary electronegative surface. With the present modelling study we conclude that the principal

  9. A molecular modeling study of inhibitors of nuclear factor kappa-B (p50)--DNA binding.

    PubMed

    Pande, Vineet; Sharma, Rakesh K; Inoue, Jun-Ichiro; Otsuka, Masami; Ramos, Maria J

    2003-12-01

    Nuclear Factor-kappa B (NF-kappaB) is an inducible transcription factor of the Rel family, and is sequestered in the cytoplasm by the IkappaB family of proteins. NF-kappaB can exist in several dimeric forms, but the p50/p65 heterodimer is the predominant one. Activation of NF-kappaB by a range of stimuli including viral products, and oxidative stress, leads to phosphorylation and proteasome dependent degradation of IkappaB, leading to the release of free NF-kappaB. This free NF-kappaB then binds to its target sites (KB sites in the DNA) to initiate transcription. These kappaB sites are also present in the Long Terminal Repeat (LTR) of HIV-1, and hence NF-kappaB (p50 subunit) binding to LTR-DNA is critical in viral replication. Targeting direct p50-DNA binding, in this regard, is a novel approach to design anti-HIV gene expression inhibitors, which do not have the problem of resistance unlike in other anti-HIV strategies. The present study is a part of our search for leads for the specific inhibition of p50-DNA binding. We have been experimentally studying different types of these inhibitors, and in this work, we attempted to get a common definition of their structural mechanism onto p50-DNA binding. Using three different classes of inhibitors, we modelled their association with the DNA-Binding Region (DBR) of the p50 subunit of NF-kappaB. Docking studies were carried out using a genetic algorithm based program (GOLD). Further, to compare electrostatic complementarity in the association of the inhibitors with the DBR, Molecular Electrostatic Potentials (MEPs) were generated for the DBR and each inhibitor. The results of docking revealed a strong network of hydrogen bonding interactions for every active inhibitor, and the contrary for the less active ones. Further, the MEPs revealed that the DBR of p50 represents a surface of electropositive potential, and the active inhibitors represent a complementary electronegative surface. With the present modelling study we

  10. Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns.

    PubMed

    Sommers, Cynthia D; Ye, Hongping; Kolinski, Richard E; Nasr, Moheb; Buhse, Lucinda F; Al-Hakim, Ali; Keire, David A

    2011-11-01

    We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M(w)) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A(2)) for each sample prior to molecular weight assessment. For UFH, a mean ± standard deviation value for M(w) of 16,773 ± 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M(w) values for dalteparin, tinzaparin, and enoxaparin of 6,717 ± 71 (n = 4), 6,670 ± 417 (n = 3), and 3,959 ± 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 ± 643 (n = 20), 5,845 ± 45 (n = 4), 6,049 ± 95 (n = 3), and 4,772 ± 69 (n = 3), respectively. These orthogonal measurements are the first M(w) results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity.

  11. The influence of FGF2 high molecular weight (HMW) isoforms in the development of cardiac ischemia-reperfusion injury

    PubMed Central

    Liao, Siyun; Bodmer, Janet R.; Azhar, Mohamad; Newman, Gilbert; Coffin, J. Douglas; Doetschman, Thomas; Schultz, Jo El J.

    2010-01-01

    Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low [LMW] and high molecular weight [HMW]), which are localized to different cellular compartments, indicating unique biological activity. We previously showed that the LMW isoform is important in protecting the heart from myocardial dysfunction associated with ischemia-reperfusion (I/R) injury, but the roles of the HMW isoforms remain unknown. To elucidate the role of HMW isoforms in I/R and cardioprotection, hearts from novel mouse models,in which the murine FGF2 HMWs are knocked out (HMWKO) or the human FGF2 24 kDa HMW isoform is overexpressed (HMW Tg) and their wildtype (Wt) or non-transgenic (NTg) cohorts were subjected to an ex vivo work-performing heart model of I/R. There was a significant improvement in post-ischemic recovery of cardiac function in HMWKO hearts (76±5%, p<0.05) compared to Wt hearts (55±5%), with a corresponding decrease in HMW Tg function (line 20: 38±6% and line 28: 33±4%, p<0.05) compared to non-transgenic hearts (68±9%). FGF2 LMW isoform was secreted from Wt and HMWKO hearts during I/R, and a FGF receptor (FGFR) inhibitor, PD173074 caused a decrease in cardiac function when administered in I/R in Wt and FGF2 HMWKO hearts (p<0.05), indicating that FGFR is involved in FGF2 LMW isoform's biological effect in ischemia-reperfusion injury. Moreover, overexpression of HMW isoform reduced FGFR1 phosphorylation/activation with no further decrease in the phosphorylation state in the presence of the FGFR inhibitor. Overall, our data indicate that HMW isoforms have a detrimental role in the development of post-ischemic myocardial dysfunction. PMID:20116383

  12. Size and shape of soil humic acids estimated by viscosity and molecular weight.

    PubMed

    Kawahigashi, Masayuki; Sumida, Hiroaki; Yamamoto, Kazuhiko

    2005-04-15

    Ultrafiltration fractions of three soil humic acids were characterized by viscometry and high performance size-exclusion chromatography (HPSEC) in order to estimate shapes and hydrodynamic sizes. Intrinsic viscosities under given solute/solvent/temperature conditions were obtained by extrapolating the concentration dependence of reduced viscosities to zero concentration. Molecular mass (weight average molecular weight (M (w)) and number average molecular weight (M (n))) and hydrodynamic radius (R(H)) were determined by HPSEC using pullulan as calibrant. Values of M (w) and M (n) ranged from 15 to 118 x 10(3) and from 9 to 50 x 10(3) (g mol(-1)), respectively. Polydispersity, as indicated by M (w)/M (n), increased with increasing filter size from 1.5 to 2.4. The hydrodynamic radii (R(H)) ranged between 2.2 and 6.4 nm. For each humic acid, M (w) and [eta] were related. Mark-Houwink coefficients calculated on the basis of the M (w)-[eta] relationships suggested restricted flexible chains for two of the humic acids and a branched structure for the third humic acid. Those structures probably behave as hydrated sphere colloids in a good solvent. Hydrodynamic radii of fractions calculated from [eta] using Einstein's equation, which is applicable to hydrated sphere colloids, ranged from 2.2 to 7.1 nm. These dimensions are fit to the size of nanospaces on and between clay minerals and micropores in soil particle aggregates. On the other hand, the good agreement of R(H) values obtained by applying Einstein's equation with those directly determined by HPSEC suggests that pullulan is a suitable calibrant for estimation of molecular mass and size of humic acids by HPSEC.

  13. Effect of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme.

    PubMed

    Morgenstern, Josefine; Baumann, Pascal; Brunner, Carina; Hubbuch, Jürgen

    2017-03-15

    During production, purification, formulation, and storage proteins for pharmaceutical or biotechnological applications face solution conditions that are unfavorable for their stability. Such harmful conditions include extreme pH changes, high ionic strengths or elevated temperatures. The characterization of the main influencing factors promoting undesired changes of protein conformation and aggregation, as well as the manipulation and selective control of protein stabilities are crucially important to biopharmaceutical research and process development. In this context PEGylation, i.e. the covalent attachment of polyethylene glycol (PEG) to proteins, represents a valuable strategy to improve the physico-chemical properties of proteins. In this work, the influence of PEG molecular weight and PEGylation degree on the physical stability of PEGylated lysozyme is investigated. Specifically, conformational and colloidal properties were studied by means of high-throughput melting point determination and automated generation of protein phase diagrams, respectively. Lysozyme from chicken egg-white as a model protein was randomly conjugated to 2kDa, 5kDa and 10kDa mPEG-aldehyde and resulting PEGamer species were purified by chromatographic separation. Besides protein stability assessment, residual enzyme activities were evaluated employing a Micrococcus lysodeikticus based activity assay. PEG molecules with lower molecular weights and lower PEGylation degrees resulted in higher residual activities. Changes in enzyme activities upon PEGylation have shown to result from a combination of steric hindrance and molecular flexibility. In contrast, higher PEG molecular weights and PEGylation degrees enhanced conformational and colloidal stability. By PEGylating lysozyme an increase of the protein solubility by more than 11-fold was achieved.

  14. Content and molecular-weight distribution of dietary fiber components in whole-grain rye flour and bread.

    PubMed

    Andersson, Roger; Fransson, Gunnel; Tietjen, Markus; Aman, Per

    2009-03-11

    Content of dietary fiber and dietary fiber components in whole-grain rye (n = 18) were analyzed. The average total content, when fructan was included, was for dietary fiber 19.9% (range of 18.7-22.2%) and for extractable dietary fiber 7.4% (range of 6.9-7.9%). Arabinoxylan was the main dietary fiber component, with an average total content of 8.6%, followed by fructan (4.1%). During baking of whole-grain rye bread, only small changes in total content of arabinoxylan, arabinogalactan, and beta-glucan occurred, while the content of resistant starch increased and the content of fructan decreased in a baking-method-dependent manner. The molecular-weight distribution of extractable arabinoxylan in the flour was analyzed with a new method and ranged from 4 x 10(4) to 9 x 10(6) g/mol, with a weight average molecular weight of about 2 x 10(6) g/mol. During crisp bread making, only a limited degradation of arabinoxylan molecular weight was detected, while a notable degradation was observed in sour-dough bread. The molecular weight of extractable beta-glucan in the whole-grain rye flour ranged from 10(4) to 5 x 10(6) g/mol, with a weight average molecular weight of 0.97 x 10(6) g/mol. During bread making, the molecular weight of the beta-glucan was substantially degraded.

  15. Furoquinoline Alkaloids from the Leaves of Evodia lepta as Potential Cholinesterase Inhibitors and their Molecular Docking.

    PubMed

    Sichaem, Jirapast; Rojpitikul, Thanawan; Sawasdee, Pattara; Lugsannangarm, Kiattisak; Santi, Tip-pyang

    2015-08-01

    Nine furoquinoline alkaloids (1-9) were isolated from the leaves of Evodia lepta based on bioassay-guided fractionation and chromatographic techniques. All isolates were evaluated for their cholinesterase (ChEs) inhibitory activities, in which kokusaginine (7) and melineurine (5) exhibited the highest activity toward AChE and BChE, respectively. Lineweaver-Burk plots indicated that 5 and 7 were mixed mode inhibitors of both ChE enzymes. Molecular docking studies on the binding sites of AChE and BChE were performed in order to afford a molecular insight into the mode of action of these active compounds. From this study these compounds have emerged as promising molecules for Alzheimer's disease therapy.

  16. Indazoles as potential c-Met inhibitors: design, synthesis and molecular docking studies.

    PubMed

    Ye, Lianbao; Ou, Xiaomin; Tian, Yuanxin; Yu, Bangwei; Luo, Yan; Feng, Binghong; Lin, Hansen; Zhang, Jiajie; Wu, Shuguang

    2013-07-01

    Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of indazoles were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibition on c-Met and compound 4d showed highest activity against c-Met with IC50 value of 0.17 μM in TR-FRET-based assay and IC50 value of 5.45 μM in cell-based assay as compared to other tested compounds. Molecular docking experiments verified the results and explained the molecular mechanism of pretty activities to c-Met.

  17. Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

    PubMed

    Islam, Md Ataul; Pillay, Tahir S

    2017-01-21

    In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB.

  18. A Critique of Asphaltene Fluorescence Decay and Depolarization-Based Claims about Molecular Weight and Molecular Architecture

    SciTech Connect

    Strausz,O.; Safarik, I.; Lown, E.; Morales-Izquierdo, A.

    2008-01-01

    Relying on experimental and theoretical data available from the literature, it is shown that the conclusions derived from measurements of fluorescence decay and depolarization kinetic times as reported in a series of papers over the past decade are egregiously wrong. To start with, the decay time measurements were done with inappropriate instrumentation which resulted in misleading results. Misinterpretation of the results led to the mistaken conclusion that bichromophoric type molecules are absent from petroleum asphaltene and therefore the architecture of the asphaltene molecule features a single condensed cyclic core spiked with some alkyl chains, in spite of irrefutable chemical evidence to the contrary. It was further concluded that if the asphaltene core is a single condensed ring, then the fluorescence depolarization with rotational correlation time method is applicable for the molecular weight determination of asphaltene. This is definitely not so, since, regardless of any other considerations, asphaltene is a mixture of a plethora of different, unknown components, with unknown concentrations along with innumerable different, unknown and some known chromophores portraying widely different absorption coefficients, fluorescence quantum yields, and kinetic decay times. Consequently, asphaltene fluorescence is a highly complex function of the above attributes and as such it is a totally unsuitable property for its molecular weight determination. The injection of an incorrect, single condensed ring core architecture for asphaltene has caused some confusion in asphaltene chemistry that has now hopefully been settled.

  19. Effect of gamma irradiation on the friction and wear of ultrahigh molecular weight polyethylene

    NASA Technical Reports Server (NTRS)

    Jones, W. R.; Hady, W. F.; Crugnola, A.

    1981-01-01

    The effect of sterilization gamma irradiation on the friction and wear properties of ultrahigh molecular weight polyethylene (UHMWPE) sliding against stainless steel 316L in dry air at 23 C is investigated, the results to be used in the development of artificial joints which are to surgically replace diseased human joints. A pin-on-disk sliding friction apparatus is used, a constant sliding speed in the range 0.061-0.27 m/s is maintained, a normal load of 1 kgf is applied with dead weight, and the irradiation dose levels are: 0, 2.5, and 5.0 Mrad. Wear and friction data and conditions for each of the ten tests are summarized, and include: (1) wear volume as a function of the sliding distance for the irradiation levels, (2) incremental wear rate, and (3) coefficient of friction as a function of the sliding distance. It is shown that (1) the friction and wear properties of UHMWPE are not significantly changed by the irradiation doses of 2.5 and 5.0 Mrad, (2) the irradiation increases the amount of insoluble gel as well as the amount of low molecular weight material, and (3) after run-in the wear rate is either steady or gradually decreases as a function of the sliding distance.

  20. Dextran: Influence of Molecular Weight in Antioxidant Properties and Immunomodulatory Potential

    PubMed Central

    Soeiro, Vinicius C.; Melo, Karoline R. T.; Alves, Monique G. C. F.; Medeiros, Mayara J. C.; Grilo, Maria L. P. M.; Almeida-Lima, Jailma; Pontes, Daniel L.; Costa, Leandro S.; Rocha, Hugo A. O.

    2016-01-01

    Dextrans (α-d-glucans) extracted from Leuconostoc mesenteroides, with molecular weights (MW) of 10 (D10), 40 (D40) and 147 (D147) kDa, were evaluated as antioxidant, anticoagulant and immunomodulatory drugs for the first time. None presented anticoagulant activity. As for the antioxidant and immunomodulatory tests, a specific test showed an increase in the dextran activity that was proportional to the increase in molecular weight. In a different assay, however, activity decreased or showed no correlation to the MW. As an example, the reducing power assay showed that D147 was twice as potent as other dextrans. On the other hand, all three samples showed similar activity (50%) when it came to scavenging the OH radical, whereas only the D10 sample showed sharp activity (50%) when it came to scavenging the superoxide ion. D40 was the single dextran that presented with immunomodulatory features since it stimulated the proliferation (~50%) of murine macrophages (RAW 264.7) and decreased the release of nitric oxide (~40%) by the cells, both in the absence and presence of lipopolysaccharides (LPS). In addition, D40 showed a greater scavenging activity (50%) for the hydrogen peroxide, which caused it to also be the more potent dextran when it came to inhibiting lipid peroxidation (70%). These points toward dextrans with a 40 kDa weight as being ideal for antioxidant and immunomodulatory use. However, future studies with the D40 and other similarly 40 kDa dextrans are underway to confirm this hypothesis. PMID:27548151

  1. Molecular weight determination of block copolymers by pulsed gradient spin echo NMR.

    PubMed

    Barrère, Caroline; Mazarin, Michaël; Giordanengo, Rémi; Phan, Trang N T; Thévand, André; Viel, Stéphane; Charles, Laurence

    2009-10-01

    Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) is the technique of choice to achieve molecular weight data for synthetic polymers. Because the success of a MALDI-MS analysis critically depends on a proper matrix and cation selection, which in turn relates closely to the polymer chemical nature and size, prior estimation of the polymer size range strongly helps in rationalizing MALDI sample preparation. We recently showed how pulsed gradient spin echo (PGSE) nuclear magnetic resonance could be used as an advantageous alternative to size exclusion chromatography, to rationalize MALDI sample preparation and confidently interpret MALDI mass spectra for homopolymers. Our aim here is to extend this methodology to the demanding case of amphiphilic block copolymers, for which obtaining prior estimates on the Mw values appears as an even more stringent prerequisite. Specifically, by studying poly(ethylene oxide) polystyrene block copolymers of distinct molecular weights and relative block weight fractions, we show how PGSE data can be used to derive the block Mw values. In contrast to homopolymers, such determination requires not only properly recorded calibration curves for each of the polymers constituting the block copolymers but also an appropriate hydrodynamic model to correctly interpret the diffusion data.

  2. Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1.

    PubMed

    Salah, R; Michaud, P; Mati, F; Harrat, Z; Lounici, H; Abdi, N; Drouiche, N; Mameri, N

    2013-01-01

    In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight-activity relationship and an electrostatic interaction-activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

  3. Combinations of reverse transcriptase, protease, and integrase inhibitors can be synergistic in vitro against drug-sensitive and RT inhibitor-resistant molecular clones of HIV-1.

    PubMed

    Beale, K K; Robinson, W E

    2000-06-01

    Combinations of anti-HIV agents including one or two reverse transcriptase inhibitors with a protease inhibitor are potent and effective. However, toxicities, costs and the emergence of drug-resistant organisms have compromised their long-term efficacy in people. A next, likely, target for anti-HIV therapy is HIV-1 integrase. Viral integration, catalyzed by integrase, is absolutely required for HIV replication. L-chicoric acid is a potent and selective inhibitor of HIV-1 integrase that also inhibits HIV-1 replication in cell culture. As a first step in understanding the potential role for integrase inhibitors in clinical medicine, the activities of L-chicoric acid alone and in combination with 2', 3'-dideoxycytidine, zidovudine, and a protease inhibitor, nelfinavir, were tested in vitro against molecular clones of HIV-1 resistant to reverse transcriptase inhibitors. L-chicoric acid was equally effective against a wild-type clone of HIV-1, HIV(NL4-3), or against HIV-1 resistant to either zidovudine or dideoxycytidine. L-chicoric acid was largely synergistic with zidovudine and synergistic with both dideoxycytidine and nelfinavir.

  4. Molecular Size and Weight of Asphaltene and Asphaltene Solubility Fractions from Coals, Crude Oils and Bitumen

    SciTech Connect

    Badre,S.; Goncalves, C.; Norinaga, K.; Gustavson, G.; Mullins, O.

    2005-01-01

    The molecular weight of asphaltenes has been a controversy for several decades. In recent years, several techniques have converged on the size of the fused ring system; indicating that chromophores in virgin crude oil asphaltenes typically have 4-10 fused rings. Consequently, the molecular weight debate is equivalent to determining whether asphaltenes are monomeric (one fused-ring system per molecule) or whether they are polymeric. Time-resolved fluorescence depolarization (FD) is employed here to interrogate the absolute size of asphaltene molecules and to determine the relation of the size of the fused ring system to that of the corresponding molecule. Coal, petroleum and bitumen asphaltenes are compared. Molecular size of coal asphaltenes obtained here by FD-determined rotational diffusion match closely with Taylor-dispersion-derived translational diffusion measurements with UV absorption. Coal asphaltenes are smaller than petroleum asphaltenes. N-methyl pyrrolidinone (NMP) soluble and insoluble fractions are examined. NMP soluble and insoluble fractions of asphaltenes are monomeric. It is suggested that the 'giant' asphaltene molecules reported from SEC studies using NMP as the eluting solvent may actually be the expected flocs of asphaltene which are not soluble in NMP. Data is presented that intramolecular electronic relaxation in asphaltenes does not perturb FD results.

  5. Purification and properties of molecular-weight variants of human placental alkaline phosphatase

    PubMed Central

    Ghosh, Nimai K.; Fishman, William H.

    1968-01-01

    1. Alkaline phosphatase of human placenta was purified by a procedure involving homogenization with tris buffer, pH8·6, extraction with butanol, ammonium sulphate fractionation, exposure to heat, ethanol fractionation, gel filtration, triethylaminoethylcellulose anion-exchange chromatography, continuous curtain electrophoresis on paper and equilibrium dialysis. Methods for both laboratory-scale and large-scale preparation were devised. 2. Two major molecular-weight variants designated A and B were separated by molecular sieving with Sephadex G-200 and variant A was purified 4000-fold. 3. Variant B, which comes off the Sephadex G-200 column before variant A, is the electrophoretically slower-moving species on starch gel and is quite heterogeneous. 4. Purified variant A was fairly homogeneous on the basis of electrophoretic studies on starch gel and Sephadex gel, ultracentrifugation and immunodiffusion. 5. The respective molecular weights for variants A and B were 70000 and over 200000 on the basis of sucrose-density-gradient ultracentrifugation. Variant A exhibited a sedimentation coefficient of 4·2s. 6. Crystalline variant B could be converted into fast-moving variant A and vice versa. 7. Kinetic studies indicated no difference between the two variants. These include linear rates of hydrolysis, pH optimum, Michaelis constants and uncompetitive stereospecific l-phenylalanine inhibition. 8. The amino acid compositions of variants A and B and of placental albumin were determined. ImagesFig. 3.Fig. 5.Fig. 7.Fig. 8.Fig. 9. PMID:4970595

  6. A low molecular weight polysaccharide isolated from Agaricus blazei suppresses tumor growth and angiogenesis in vivo.

    PubMed

    Niu, Y C; Liu, J C; Zhao, X M; Wu, X X

    2009-01-01

    Previous studies indicated that the low molecular weight polysaccharide extracts from Agaricus blazei are potential antitumor agents or adjuvant in tumor treatment. In this study, we investigated the antitumor activity of LMPAB, a low molecular weight polysaccharide isolated from Agaricus blazei, and the molecular mechanisms of its antitumor activity. The antitumor effect of LMPAB was examined using mouse sarcoma 180 (S180) xenograft models. Antiangiogenic effect of LMPAB was determined by chicken embryo chorioallantoic membrane (CAM) angiogenesis and Matrigel-induced neovascularization in vivo models. The mRNA and protein levels of vascular endothelial growth factor (VEGF) were assessed using real-time reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assays. Tumor inhibitory rates in the S180 xenograft models were 9.7, 23.9, and 33.0%, respectively, after administration of LMPAB at dose of 50, 100, and 200 mg/kg/day for 2 weeks. LMPAB also inhibited angiogenesis in the CAM model and Matrigel-induced neovascularization in C57BL/6 mice. The mRNA and protein levels of VEGF in tumor tissues were significantly down-regulated in the BALB/c mice received LMPAB treatment. Furthermore, significant down-regulation of serum VEGF levels was also observed in the mice. Our data suggest that LMPAB might be a promising agent for tumor therapy, and the antitumor and antiangiogenic effects of LMPAB may be related with down-regulation of VEGF.

  7. Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis.

    PubMed

    Kay, Richard; Barton, Chris; Ratcliffe, Lucy; Matharoo-Ball, Balwir; Brown, Pamela; Roberts, Jane; Teale, Phil; Creaser, Colin

    2008-10-01

    A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses.

  8. Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study.

    PubMed

    Antony, Priya; Vijayan, Ranjit

    2016-01-01

    Apoptosis is a highly regulated process crucial for maintaining cellular homeostasis and development. The B-cell lymphoma 2 (Bcl-2) family of proteins play a crucial role in regulating apoptosis. Overexpressed Bcl-2 proteins are associated with the development and progression of several human cancers. Annona muricata is a tropical plant that belongs to the Annonaceae family and is well known for its anticancer properties. In this study, molecular docking and simulations were performed to investigate the inhibitory potential of phytochemicals present in A. muricata against antiapoptotic proteins of the Bcl-2 family including Bcl-2, B-cell lymphoma extra-large (Bcl-Xl), and Mcl-1. Docking results revealed that the acetogenins, such as annomuricin A, annohexocin, muricatocin A, annomuricin-D-one, and muricatetrocin A/B, exhibited strong binding interactions with Bcl-Xl when compared to Bcl-2 and Mcl-1. Binding score and interactions of these acetogenins were notably better than those of currently available synthetic and natural inhibitors. Molecular dynamics simulations of the top-scoring lead molecules established that these molecules could bind strongly and consistently in the active site of Bcl-Xl. These results suggest that acetogenins could be explored as selective natural inhibitors of Bcl-Xl that could assist in promoting the intrinsic pathway of apoptosis.

  9. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study

    PubMed Central

    Antony, Priya; Vijayan, Ranjit

    2015-01-01

    Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors. PMID:26384019

  10. [Low-molecular cytolysins and trypsin inhibitors from sea anemone Radianthus macrodactylus. Isolation and partial characterization].

    PubMed

    Zykova, T A; Monastyrnaia, M M; Apalikova, O V; Shvets, T V; Kozlovskaia, E P

    1998-07-01

    Two low-molecular cytolytic toxins (RmI and RmII) and four trypsin inhibitors were isolated from the aqueous extract of sea anemone Radianthus macrodactylus. The method of isolation involved precipitation with acetone, gel filtration on acrylex P-4, ion-exchange chromatography on CM-32 cellulose, affinity chromatography on trypsin-binding sepharose 4B, ion exchange chromatography on an Ultrapore TSK CM-3SW column, and reversed phase HPLC on a Silasorb C18 column. RmI, RmII, and JnI inhibitor displayed molecular masses 5100, 6100, and 7100 Da, respectively, when subjected to SDS-PAGE. The isoelectric points were 9.2 and 9.3 for RmI and RmII, respectively. The amino acid composition and N-terminal amino acid residue (glycine) were determined for RmI, RmII, and JnI. Both proteins were nontoxic to mice and crabs. Hemolytic activity was determined to be 25 and 20 HU/mg for RmI and RmII, respectively, and their action on erythrocyte membrane was not inhibited by exogenous sphingomyelin. RmI and RmII exhibited antihistamine activity.

  11. Molecular insights on TNKS1/TNKS2 and inhibitor-IWR1 interactions.

    PubMed

    Kirubakaran, Palani; Kothandan, Gugan; Cho, Seung J; Muthusamy, Karthikeyan

    2014-02-01

    Tankyrases (TNKS) belong to the poly(ADP-ribose)polymerase (PARP) protein super family and play a vital role in the Wnt/β-catenin signaling pathway. TNKS is a potential target for therapeutic intervention against various cancers, heritable diseases (e.g. cherubism) and implications in the replication of herpes simplex virus (HSV). The recent discovery of the structure of TNKS with an IWR1 inhibitor has provided insight into the binding modes which are specific for the TNKS protein which will aid in the development of drugs that are specific for the TNKS protein. The current study investigates molecular interactions between the induced pocket of TNKS1 and TNKS2 with an IWR1 compound using computational approaches. Molecular docking analysis of IWR1 at the induced pocket of TNKS1 and TNKS2 was performed. The resulting protein-ligand complexes were simulated for a timescale of 100 ns. Results revealed the stable binding of IWR1 at the induced pocket of TNKS1 and TNKS2 proteins. Apart from active site amino acids, π-π stack paring interactions were also crucial for the protein-ligand binding and stability of the complex. Further, energy-optimized pharmacophore mapping was performed and the resulting pharmacophore model contained a four (TNKS1-IWR1) and five (TNKS2-IWR1) featured sites. Based on the pharmacophore models, the best inhibitors were screened from the ZINC natural product compound database and these could be used as potential drugs against TNKS1 and TNKS2.

  12. Acetogenins from Annona muricata as potential inhibitors of antiapoptotic proteins: a molecular modeling study

    PubMed Central

    Antony, Priya; Vijayan, Ranjit

    2016-01-01

    Apoptosis is a highly regulated process crucial for maintaining cellular homeostasis and development. The B-cell lymphoma 2 (Bcl-2) family of proteins play a crucial role in regulating apoptosis. Overexpressed Bcl-2 proteins are associated with the development and progression of several human cancers. Annona muricata is a tropical plant that belongs to the Annonaceae family and is well known for its anticancer properties. In this study, molecular docking and simulations were performed to investigate the inhibitory potential of phytochemicals present in A. muricata against antiapoptotic proteins of the Bcl-2 family including Bcl-2, B-cell lymphoma extra-large (Bcl-Xl), and Mcl-1. Docking results revealed that the acetogenins, such as annomuricin A, annohexocin, muricatocin A, annomuricin-D-one, and muricatetrocin A/B, exhibited strong binding interactions with Bcl-Xl when compared to Bcl-2 and Mcl-1. Binding score and interactions of these acetogenins were notably better than those of currently available synthetic and natural inhibitors. Molecular dynamics simulations of the top-scoring lead molecules established that these molecules could bind strongly and consistently in the active site of Bcl-Xl. These results suggest that acetogenins could be explored as selective natural inhibitors of Bcl-Xl that could assist in promoting the intrinsic pathway of apoptosis. PMID:27110097

  13. Molecular dynamics and Monte Carlo simulations for protein–ligand binding and inhibitor design☆

    PubMed Central

    Cole, Daniel J.; Tirado-Rives, Julian; Jorgensen, William L.

    2014-01-01

    Background Non-nucleoside inhibitors of HIV reverse transcriptase are an important component of treatment against HIV infection. Novel inhibitors are sought that increase potency against variants that contain the Tyr181Cys mutation. Methods Molecular dynamics based free energy perturbation simulations have been run to study factors that contribute to protein–ligand binding, and the results are compared with those from previous Monte Carlo based simulations and activity data. Results Predictions of protein–ligand binding modes are very consistent for the two simulation methods, which are attributed to the use of an enhanced sampling protocol. The Tyr181Cys binding pocket supports large, hydrophobic substituents, which is in good agreement with experiment. Conclusions Although some discrepancies exist between the results of the two simulation methods and experiment, free energy perturbation simulations can be used to rapidly test small molecules for gains in binding affinity. General significance Free energy perturbation methods show promise in providing fast, reliable and accurate data that can be used to complement experiment in lead optimization projects. This article is part of a Special Issue entitled “Recent developments of molecular dynamics”. PMID:25196360

  14. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.

    PubMed

    Antony, Priya; Vijayan, Ranjit

    2015-01-01

    Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR), the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger), Curcuma longa (turmeric) Allium sativum (garlic) and Trigonella foenum graecum (fenugreek). Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.

  15. Condensed Tannins from Ficus virens as Tyrosinase Inhibitors: Structure, Inhibitory Activity and Molecular Mechanism

    PubMed Central

    Chai, Wei-Ming; Feng, Hui-Ling; Zhuang, Jiang-Xing; Chen, Qing-Xi

    2014-01-01

    Condensed tannins from Ficus virens leaves, fruit, and stem bark were isolated and their structures characterized by 13C nuclear magnetic resonance spectrometry, high performance liquid chromatography electrospray ionization mass spectrometry, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The results showed that the leaves, fruit, and stem bark condensed tannins were complex mixtures of homo- and heteropolymers of B-type procyanidins and prodelphinidins with degrees of polymerization up to hexamer, dodecamer, and pentadecamer, respectively. Antityrosinase activities of the condensed tannins were studied. The results indicated that the condensed tannins were potent tyrosinase inhibitors. The concentrations for the leaves, fruit, and stem bark condensed tannins leading to 50% enzyme activity were determined to be 131.67, 99.89, and 106.22 μg/ml on monophenolase activity, and 128.42, 43.07, and 74.27 μg/ml on diphenolase activity. The inhibition mechanism, type, and constants of the condensed tannins on the diphenolase activity were further investigated. The results indicated that the condensed tannins were reversible and mixed type inhibitors. Fluorescence quenching, copper interacting, and molecular docking techniques were utilized to unravel the molecular mechanisms of the inhibition. The results showed that the hydroxyl group on the B ring of the condensed tannins could chelate the dicopper irons of the enzyme. Moreover, the condensed tannins could reduce the enzyme product o-quinones into colourless compounds. These results would contribute to the development and design of antityrosinase agents. PMID:24637701

  16. Role of receptor for hyaluronic acid-mediated motility (RHAMM) in low molecular weight hyaluronan (LMWHA)-mediated fibrosarcoma cell adhesion.

    PubMed

    Kouvidi, Katerina; Berdiaki, Aikaterini; Nikitovic, Dragana; Katonis, Pavlos; Afratis, Nikos; Hascall, Vincent C; Karamanos, Nikos K; Tzanakakis, George N

    2011-11-04

    Hyaluronan (HA) modulates key cancer cell functions through interaction with its CD44 and receptor for hyaluronic acid-mediated motility (RHAMM) receptors. HA was recently found to regulate the migration of fibrosarcoma cells in a manner specifically dependent on its size. Here, we investigated the effect of HA/RHAMM signaling on the ability of HT1080 fibrosarcoma cells to adhere onto fibronectin. Low molecular weight HA (LMWHA) significantly increased (p ≤ 0.01) the adhesion capacity of HT1080 cells, which high molecular weight HA inhibited. The ability of HT1080 RHAMM-deficient cells, but not of CD44-deficient ones, to adhere was significantly decreased (p ≤ 0.001) as compared with control cells. Importantly, the effect of LMWHA on HT1080 cell adhesion was completely attenuated in RHAMM-deficient cells. In contrast, adhesion of RHAMM-deficient cells was not sensitive to high molecular weight HA treatment, which identifies RHAMM as a specific conduit of the LMWHA effect. Western blot and real time-PCR analyses indicated that LMWHA significantly increased RHAMM transcript (p ≤ 0.05) and protein isoform levels (53%, 95 kDa; 37%, 73 kDa) in fibrosarcoma cells. Moreover, Western blot analyses showed that LMWHA in a RHAMM-dependent manner enhanced basal and adhesion-dependent ERK1/2 and focal adhesion kinase (FAK) phosphorylation in HT1080 cells. Utilization of a specific ERK1/2 inhibitor completely inhibited (p ≤ 0.001) LMWHA-dependent adhesion, suggesting that ERK1/2 is a downstream effector of LMWHA/RHAMM signaling. Likewise, the utilization of the specific ERK1 inhibitor resulted in a strong down-regulation of FAK activation in HT1080 cells, which identifies ERK1/2 as a FAK upstream activator. In conclusion, our results suggest that RHAMM/HA interaction regulates fibrosarcoma cell adhesion via the activation of FAK and ERK1/2 signaling pathways.

  17. Rates of thrombin acylation and deacylation upon reaction with low molecular weight acylating agents, carbamylating agents and carbonylating agents.

    PubMed

    Brown, A D; Powers, J C

    1995-08-01

    Acylated derivatives of thrombin have been made using low molecular weight acylating agents, carbamylating agents and carbonylating agents. The compounds used to acylate the active site serine include isatoic anhydrides, benzoxazinones, benzylisocyanate, N-(benzylcarbonyloxy)succinimide and p-(dimethylamino)benzoylimidazolide. The rates of acylation and deacylation were determined. The best overall inhibitors of thrombin are 2-ethoxy-4H-3,1-benzoxazin-4-one, isatoic anhydride and tert-butyl-2,4-dioxo-2H-3,1-benzoxazine-1(4H)-acetate, which have k2/Ki values of 52,700 M-1s-1, 48,900 M-1s-1 and 5400 M-1s-1, respectively. The carbamyl derivative of thrombin formed with benzylisocyanate had the slowest rate of deacylation (2.3 x 10(-7) s-1), while the ester derivative formed with 2-(N,N-dimethylamino)methylimino-4H-3,1-benzoxazin-4-one had the fastest rate of deacylation (1.9 x 10(-4) s-1).

  18. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin.

    PubMed

    Cheng, Wenming; Dahmani, Fatima Zohra; Zhang, Juan; Xiong, Hui; Wu, Yuanyuan; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-02-17

    Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH. The resulting LMWH-UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200-250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH-UA. Meanwhile, the in vivo antitumor effect of LMWH-UA was also evaluated using a B16F10 mouse melanoma model. LMWH-UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH-UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH-UA as a new therapeutic remedy for cancer therapy.

  19. Anti-angiogenic activity and antitumor efficacy of amphiphilic twin drug from ursolic acid and low molecular weight heparin

    NASA Astrophysics Data System (ADS)

    Cheng, Wenming; Zohra Dahmani, Fatima; Zhang, Juan; Xiong, Hui; Wu, Yuanyuan; Yin, Lifang; Zhou, Jianping; Yao, Jing

    2017-02-01

    Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH. The resulting LMWH-UA conjugate as an amphiphilic twin drug showed reduced anticoagulant activity and could also self-assemble into nanomicelles with a mean particle size ranging from 200-250 nm. An in vitro endothelial tubular formation assay and an in vivo Matrigel plug assay were performed to verify the anti-angiogenic potential of LMWH-UA. Meanwhile, the in vivo antitumor effect of LMWH-UA was also evaluated using a B16F10 mouse melanoma model. LMWH-UA nanomicelles were shown to inhibit angiogenesis both in vitro and in vivo. In addition, the i.v. administration of LMWH-UA to the B16F10 tumor-bearing mice resulted in a significant inhibition of tumor growth as compared to the free drug solutions. These findings demonstrate the therapeutic potential of LMWH-UA as a new therapeutic remedy for cancer therapy.

  20. A benchmark for platelet count monitoring with low-molecular-weight heparin: expanding implementation of National Patient Safety Goals.

    PubMed

    Spinler, Sarah A

    2009-09-01

    Practitioners in US hospitals are implementing anticoagulation dosing and monitoring protocols to improve the safety of anticoagulation, consistent with National Patient Safety Goal 03.05.01. An audit of the Utrecht Patient Oriented Database of patients treated with low-molecular-weight heparin (LMWH) at the University Medical Center Utrecht revealed low compliance with platelet count monitoring as well as initial management of suspected heparin-induced thrombocytopenia (HIT). Limitations to this work included the inability to exclude other drug-induced causes of thrombocytopenia and their definition of the frequency of platelet count monitoring for compliance in patients given venous thromboembolism prophylaxis. Despite these limitations, the authors' work represents the first published report on extending the quality of heparin anticoagulation management to platelet count monitoring and evaluation for HIT in a large patient population. Clinicians should include evaluations of compliance with platelet count monitoring with unfractionated heparin and LMWH, as well as appropriateness of the initial management strategies for HIT, and direct thrombin inhibitor protocols in their patient safety practice assessments.

  1. Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps.

    PubMed

    Manfredi, Angelo A; Rovere-Querini, Patrizia; D'Angelo, Armando; Maugeri, Norma

    2017-02-01

    The protection exerted by neutrophils against invading microbes is partially mediated via the generation of neutrophil extracellular traps (NETs). In sterile conditions NETs are damaging species, enriched in autoantigens and endowed with the ability to damage the vessel wall and bystander tissues, to promote thrombogenesis, and to impair wound healing. To identify and reposition agents that can be used to modulate the formation of NETs is a priority in the research agenda. Low molecular weight heparins (LMWH) are currently used, mostly on an empirical basis, in conditions in which NETs play a critical role, such as pregnancy complications associated to autoimmune disease. Here we report that LMWHs induce a profound change in the ability of human neutrophils to generate NETs and to mobilize the content of the primary granules in response to unrelated inflammatory stimuli, such as IL-8, PMA and HMGB1. Autophagy consistently accompanies NET generation in our system and autophagy inhibitors, 3-MA and wortmannin, prevent NET generation. Pretreatment with LMWH in vitro critically jeopardizes neutrophil ability to activate autophagy, a mechanism that might contribute to neutrophil unresponsiveness. Finally, we verified that treatment of healthy volunteers with a single prophylactic dose of parnaparin abrogated the ability of neutrophils to activate autophagy and to generate NETs. Together, these results support the contention that neutrophils, and NET generation in particular, might represent a preferential target of the anti-inflammatory action of LMWH.

  2. Insights into molecular interactions between CaM and its inhibitors from molecular dynamics simulations and experimental data.

    PubMed

    González-Andrade, Martin; Rodríguez-Sotres, Rogelio; Madariaga-Mazón, Abraham; Rivera-Chávez, José; Mata, Rachel; Sosa-Peinado, Alejandro; Del Pozo-Yauner, Luis; Arias-Olguín, Imilla I

    2016-01-01

    In order to contribute to the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed the interaction of CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking and molecular dynamics (MD) simulations, and the data were compared to available experimental data. The Ca(2+)-CaM-Ligands complexes were simulated 20 ns, with CaM starting in the "open" and "closed" conformations. The analysis of the MD simulations provided insight into the conformational changes undergone by CaM during its interaction with these ligands. These simulations were used to predict the binding free energies (ΔG) from contributions ΔH and ΔS, giving useful information about CaM ligand binding thermodynamics. The ΔG predicted for the CaM's inhibitors correlated well with available experimental data as the r(2) obtained was 0.76 and 0.82 for the group of xanthones. Additionally, valuable information is presented here: I) CaM has two preferred ligand binding sites in the open conformation known as site 1 and 4, II) CaM can bind ligands of diverse structural nature, III) the flexibility of CaM is reduced by the union of its ligands, leading to a reduction in the Ca(2+)-CaM entropy, IV) enthalpy dominates the molecular recognition process in the system Ca(2+)-CaM-Ligand, and V) the ligands making more extensive contact with the protein have higher affinity for Ca(2+)-CaM. Despite their limitations, docking and MD simulations in combination with experimental data continue to be excellent tools for research in pharmacology, toward a rational design of new drugs.

  3. Computational study of Gleevec and G6G reveals molecular determinants of kinase inhibitor selectivity

    SciTech Connect

    Lin, Yen -Lin; Meng, Yilin; Huang, Lei; Roux, Benoît

    2014-10-22

    Gleevec is a potent inhibitor of Abl tyrosine kinase but not of the highly homologous c-Src kinase. Because the ligand binds to an inactive form of the protein in which an Asp-Phe-Gly structural motif along the activation loop adopts a so-called DFG-out conformation, it was suggested that binding specificity was controlled by a “conformational selection” mechanism. In this context, the binding affinity displayed by the kinase inhibitor G6G poses an intriguing challenge. Although it possesses a chemical core very similar to that of Gleevec, G6G is a potent inhibitor of both Abl and c-Src kinases. Both inhibitors bind to the DFG-out conformation of the kinases, which seems to be in contradiction with the conformational selection mechanism. To address this issue and display the hidden thermodynamic contributions affecting the binding selectivity, molecular dynamics free energy simulations with explicit solvent molecules were carried out. Relative to Gleevec, G6G forms highly favorable van der Waals dispersive interactions upon binding to the kinases via its triazine functional group, which is considerably larger than the corresponding pyridine moiety in Gleevec. Upon binding of G6G to c-Src, these interactions offset the unfavorable free energy cost of the DFG-out conformation. When binding to Abl, however, G6G experiences an unfavorable free energy penalty due to steric clashes with the phosphate-binding loop, yielding an overall binding affinity that is similar to that of Gleevec. Such steric clashes are absent when G6G binds to c-Src, due to the extended conformation of the phosphate-binding loop.

  4. Computational study of Gleevec and G6G reveals molecular determinants of kinase inhibitor selectivity

    DOE PAGES

    Lin, Yen -Lin; Meng, Yilin; Huang, Lei; ...

    2014-10-22

    Gleevec is a potent inhibitor of Abl tyrosine kinase but not of the highly homologous c-Src kinase. Because the ligand binds to an inactive form of the protein in which an Asp-Phe-Gly structural motif along the activation loop adopts a so-called DFG-out conformation, it was suggested that binding specificity was controlled by a “conformational selection” mechanism. In this context, the binding affinity displayed by the kinase inhibitor G6G poses an intriguing challenge. Although it possesses a chemical core very similar to that of Gleevec, G6G is a potent inhibitor of both Abl and c-Src kinases. Both inhibitors bind to themore » DFG-out conformation of the kinases, which seems to be in contradiction with the conformational selection mechanism. To address this issue and display the hidden thermodynamic contributions affecting the binding selectivity, molecular dynamics free energy simulations with explicit solvent molecules were carried out. Relative to Gleevec, G6G forms highly favorable van der Waals dispersive interactions upon binding to the kinases via its triazine functional group, which is considerably larger than the corresponding pyridine moiety in Gleevec. Upon binding of G6G to c-Src, these interactions offset the unfavorable free energy cost of the DFG-out conformation. When binding to Abl, however, G6G experiences an unfavorable free energy penalty due to steric clashes with the phosphate-binding loop, yielding an overall binding affinity that is similar to that of Gleevec. Such steric clashes are absent when G6G binds to c-Src, due to the extended conformation of the phosphate-binding loop.« less

  5. Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer's Disorders Using Molecular Docking and Molecular Dynamics Simulation

    PubMed Central

    Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

    2014-01-01

    Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential. PMID:25054066

  6. Identification of potential herbal inhibitor of acetylcholinesterase associated Alzheimer's disorders using molecular docking and molecular dynamics simulation.

    PubMed

    Seniya, Chandrabhan; Khan, Ghulam Jilani; Uchadia, Kuldeep

    2014-01-01

    Cholinesterase inhibitors (ChE-Is) are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA). Additionally, acetylcholinesterase (AChE) is the target for many Alzheimer's dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6) to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

  7. Low molecular weight PEI-based biodegradable lipopolymers as gene delivery vectors.

    PubMed

    Xun, Miao-Miao; Zhang, Xue-Chao; Zhang, Ji; Jiang, Qian-Qian; Yi, Wen-Jing; Zhu, Wen; Yu, Xiao-Qi

    2013-02-21

    Non-viral gene vectors play an important role in the development of gene therapy. In this report, different hydrophobic chains were introduced into low molecular weight (LMW) PEI-based biodegradable oligomers to form a series of lipopolymers (LPs), and their structure-activity relationships were studied. Results revealed that the nine polymers can condense plasmid DNA well to form nanoparticles with appropriate sizes (120-250 nm) and positive zeta-potentials (+25-40 V). In vitro experiments were carried out and it was found that LP2 showed much higher transfection efficiency both in the presence and in the absence of serum under the polymer/DNA weight ratio of 0.8 in A549 cells.

  8. Correlation between human maternal-fetal placental transfer and molecular weight of PCB and dioxin congeners/isomers.

    PubMed

    Mori, Chisato; Nakamura, Noriko; Todaka, Emiko; Fujisaki, Takeyoshi; Matsuno, Yoshiharu; Nakaoka, Hiroko; Hanazato, Masamichi

    2014-11-01

    Establishing methods for the assessment of fetal exposure to chemicals is important for the prevention or prediction of the child's future disease risk. In the present study, we aimed to determine the influence of molecular weight on the likelihood of chemical transfer from mother to fetus via the placenta. The correlation between molecular weight and placental transfer rates of congeners/isomers of polychlorinated biphenyls (PCBs) and dioxins was examined. Twenty-nine sample sets of maternal blood, umbilical cord, and umbilical cord blood were used to measure PCB concentration, and 41 sample sets were used to analyze dioxins. Placental transfer rates were calculated using the concentrations of PCBs, dioxins, and their congeners/isomers within these sample sets. Transfer rate correlated negatively with molecular weight for PCB congeners, normalized using wet and lipid weights. The transfer rates of PCB or dioxin congeners differed from those of total PCBs or dioxins. The transfer rate for dioxin congeners did not always correlate significantly with molecular weight, perhaps because of the small sample size or other factors. Further improvement of the analytical methods for dioxin congeners is required. The findings of the present study suggested that PCBs, dioxins, or their congeners with lower molecular weights are more likely to be transferred from mother to fetus via the placenta. Consideration of chemical molecular weight and transfer rate could therefore contribute to the assessment of fetal exposure.

  9. Low molecular weight quaternised chitosan (11): in vitro assessment of absorption enhancing properties.

    PubMed

    Jonker-Venter, C; Snyman, D; Janse van Rensburg, C; Jordaan, E; Schultz, C; Steenekamp, J H; Hamman, J H; Kotzé, A F

    2006-04-01

    N-Trimethyl chitosan chloride (TMC; high molecular weight) and N-trimethyl chitosan oligosaccharide (TMO; low molecular weight) with different degrees of quaternisation were synthesised and evaluated for their absorption enhancing properties across mucosal epithelia. These quaternised chitosan derivatives (0.0625% w/v-0.5% w/v) showed a significant decrease in the transepithelial electrical resistance (TEER) of cultured rabbit tracheal epithelial cell monolayers as compared to the control. The degree of quaternisation and concentration of the compounds influenced the extent of the reduction in TEER. Higher degrees of quaternisation and an increase in the concentration of the compound were associated with a more pronounced reduction in the TEER. The TMO derivatives seemed to be more effective in lowering the TEER of tracheal cell monolayers as compared to the TMC polymers. Ciliary beat frequency (CBF) is the main defence mechanism of the respiratory tract and is therefore a useful parameter in evaluating the toxicity of nasally administered drugs and additives. The effect of the synthesised chitosan derivatives on the CBF of human nasal epithelial cells at pH 7.4 was determined by a method based on an analogue contrast enhancement technique. The TMO oligomers exhibited lower inhibition of the CBF of human nasal epithelial cells compared to that of the TMC polymers. It was proposed that this reduced effect on the CBF is due to the lower viscosity and molecular weight of TMO. However, no acute toxicity was found with any of the synthesised chitosan derivatives by means of the CBF tests conducted in this study.

  10. Preparation, characterization and applications of low-molecular-weight alginate-oligochitosan nanocapsules

    NASA Astrophysics Data System (ADS)

    Wang, Ting; He, Nongyue

    2010-02-01

    The development of drug-delivering nanoparticles from natural materials for various biomedical applications is an area of great promise. However, the contradictory data on their uncontrollable diameter, unstable structure and toxic effects, highlight the need to study their preparation, characterization and cytotoxic effects in cells. In this work, nanocapsules are made from a type of W/O microemulsion system with low-molecular-weight alginate (LMWALG) and oligochitosan (OCS). The particles possess excellent biocompatibility and good biodegradability. The size of capsules is controlled and optimized by carefully adjusting the molecular weight and concentration of LMWALG and OCS. We found, from orthogonal experiments, the encapsulation time leading to a uniform size distribution with an average diameter of 136 nm. Furthermore, we found that molecular weights of LMWALG and OCS significantly influence the stability and size of capsules. The optimized nanocapsules are further used to study the drug release of BSA. Results show that the efficiency of encapsulation approximately reaches 88.4% and the concentration of BSA in phosphate-buffered solution (PBS, pH = 7.4) is well maintained at a level of 35 to 40% from 12 h to 48 h, due to the stable and slow degradation of the nanocapusules. The biocompatibility of LMWALG/OCS nanocapsules is cross-examined by cytotoxicity experiments and acute systemic toxicological tests, and they were found to enhance the survival rate of the cells from 80.30 to 95.39% in 7 days. The synthesized nanocapsules exhibit high biocompatibility, non-toxicity, biodegradation, and uniform size, providing a new potential candidate for drug releases in clinic experiments.

  11. Chitosan nanocapsules: Effect of chitosan molecular weight and acetylation degree on electrokinetic behaviour and colloidal stability.

    PubMed

    Santander-Ortega, M J; Peula-García, J M; Goycoolea, F M; Ortega-Vinuesa, J L

    2011-02-01

    In recent years, chitosan nanocapsules have shown promising results as carriers for oral drug or peptide delivery. The success in their applicability strongly depends on the stability of these colloidal systems passing through the digestive tract. In gastric fluids, clear stability comes from the high surface charge density of the chitosan shell, which is completely charged at acidic pH values. However, in the intestinal fluid (where the pH is almost neutral) the effective charge of these nanocapsules approaches zero, and the electrostatic forces cannot provide any stabilization. Despite the lack of surface charge, chitosan nanocapsules remain stable in simulated intestinal fluids. Recently, we have demonstrated that this anomalous stability (at zero charge) is owed to short-range repulsive forces that appear between hydrophilic particles when immersed in saline media. The present work examines the influence of the chitosan hydrophobicity, as well as molecular weight, in the stability of different chitosan nanocapsules. A study has been made of the size, polydispersity, electrophoretic mobility, and colloidal stability of eight core-shell nanocapsule systems, in which the chitosan-shell properties have been modified using low-molecular-weight (LMW) and high-molecular-weight (HMW) chitosan chains having different degrees of acetylation (DA). With regard to the stability mediated by repulsive hydration forces, the LMW chitosan provided the best results. In addition, contrary to initial expectations, greater stability (also mediated by hydration forces) was found in the samples formed with chitosan chains of high DA values (i.e. with less hydrophilic chitosan). Finally, a theoretical treatment was also tested to quantify the hydrophilicity of the chitosan shells.

  12. Capture, enrichment, and mass spectrometric detection of low-molecular-weight biomarkers with nanoporous silicon microparticles.

    PubMed

    Tan, Jie; Zhao, Wei-Jie; Yu, Jie-Kai; Ma, Sai; Sailor, Michael J; Wu, Jian-Min

    2012-11-01

    Mining the disease information contained in the low-molecular-weight range of a proteomic profile is becoming of increasing interest in cancer research. This work evaluates the ability of nanoporous silicon microparticles (NPSMPs) to capture, enrich, protect, and detect low-molecular-weight peptides (LMWPs) sieved from a pool of highly abundant plasma proteins. The average pore size and porosity of NPSMPs are controlled by the electrochemical preparation conditions, and the critical parameters for admission or exclusion of protein with a definite molecular weight are determined by reflectometric-interference Fourier transform spectroscopy (RIFTS). Sodium dodecyl sulfate polyacrylamide-gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis of the proteins captured by the NPSMPs show that the chemical nature of the NPSMPs surface and the solution pH also play vital roles in determining the affinity of NPSMPs for target analytes. It is found that carboxyl-terminated porous microparticles with a porosity of 26% (pore diameter around 9.0 nm) specifically fractionate, enrich and protect LMWPs sieved from either simulated samples or human serum samples. Moreover, NPSMPs containing captured peptides can be directly spotted onto a MALDI plate. When placed in a conventional MALDI matrix, laser irradiation of the particles results in the release of the target peptides confined in the nanopores, which are then ionized and detected in the MALDI experiment. As a proof-of-principle test case, mass spectra of NPSMPs prepared using serum from colorectal cancer patients and from control patients can be clearly distinguished by statistical analysis. The work demonstrates the utility of the method for discovery of biomarkers in the untapped LMWP fraction of human serum, which can be of significant value in the early diagnosis and management of diseases.

  13. Controlling Internal Organization of Multilayer Poly(methacrylic acid) Hydrogels with Polymer Molecular Weight

    DOE PAGES

    Kozlovskaya, Veronika; Zavgorodnya, Oleksandra; Ankner, John F.; ...

    2015-11-16

    Here, we report on tailoring the internal architecture of multilayer-derived poly(methacrylic acid) (PMAA) hydrogels by controlling the molecular weight of poly(N-vinylpyrrolidone) (PVPON) in hydrogen-bonded (PMAA/PVPON) layer-by-layer precursor films. The hydrogels are produced by cross-linking PMAA in the spin-assisted multilayers followed by PVPON release. We found that the thickness, morphology, and architecture of hydrogen-bonded films and the corresponding hydrogels are significantly affected by PVPON chain length. For all systems, an increase in PVPON molecular weight from Mw = 2.5 to 1300 kDa resulted in increased total film thickness. We also show that increasing polymer Mw smooths the hydrogen-bonded film surfaces butmore » roughens those of the hydrogels. Using deuterated dPMAA marker layers in neutron reflectometry measurements, we found that hydrogen-bonded films reveal a high degree of stratification which is preserved in the cross-linked films. We observed dPMAA to be distributed more widely in the hydrogen-bonded films prepared with small Mw PVPON due to the greater mobility of short-chain PVPON. Furthermore, these variations in the distribution of PMAA are erased after cross-linking, resulting in a distribution of dPMAA over about two bilayers for all Mw but being somewhat more widely distributed in the films templated with higher Mw PVPON. Finally, our results yield new insights into controlling the organization of nanostructured polymer networks using polymer molecular weight and open opportunities for fabrication of thin films with well-organized architecture and controllable function.« less

  14. Controlling Internal Organization of Multilayer Poly(methacrylic acid) Hydrogels with Polymer Molecular Weight

    SciTech Connect

    Kozlovskaya, Veronika; Zavgorodnya, Oleksandra; Ankner, John F.; Kharlampieva, Eugenia

    2015-11-16

    Here, we report on tailoring the internal architecture of multilayer-derived poly(methacrylic acid) (PMAA) hydrogels by controlling the molecular weight of poly(N-vinylpyrrolidone) (PVPON) in hydrogen-bonded (PMAA/PVPON) layer-by-layer precursor films. The hydrogels are produced by cross-linking PMAA in the spin-assisted multilayers followed by PVPON release. We found that the thickness, morphology, and architecture of hydrogen-bonded films and the corresponding hydrogels are significantly affected by PVPON chain length. For all systems, an increase in PVPON molecular weight from Mw = 2.5 to 1300 kDa resulted in increased total film thickness. We also show that increasing polymer Mw smooths the hydrogen-bonded film surfaces but roughens those of the hydrogels. Using deuterated dPMAA marker layers in neutron reflectometry measurements, we found that hydrogen-bonded films reveal a high degree of stratification which is preserved in the cross-linked films. We observed dPMAA to be distributed more widely in the hydrogen-bonded films prepared with small Mw PVPON due to the greater mobility of short-chain PVPON. Furthermore, these variations in the distribution of PMAA are erased after cross-linking, resulting in a distribution of dPMAA over about two bilayers for all Mw but being somewhat more widely distributed in the films templated with higher Mw PVPON. Finally, our results yield new insights into controlling the organization of nanostructured polymer networks using polymer molecular weight and open opportunities for fabrication of thin films with well-organized architecture and controllable function.

  15. Alkyl cross-linked low molecular weight polypropyleneimine dendrimers as efficient gene delivery vectors

    PubMed Central

    Ariaee, Faezeh Moghadam; Hashemi, Maryam; Farzad, Sara Amel; Abnous, Khalil; Ramezani, Mohammad

    2016-01-01

    Objective(s): In recent years, polypropyleneimine (PPI) dendrimers have attracted great interest as non-viral gene delivery systems because of their attractive features including highly branched architecture with number of reactive end groups. However, without being structurally modified, they are not efficient gene carriers. In the present study, generation 2 and 3 (G2 and G3) of PPI dendrimers were conjugated with alkylcarboxylate groups as linker to enhance the transfection efficiency while maintaining their low cell toxicity. Materials and Methods: First, 10-bromodecanoic acid was covalently attached to all available surface primary amines of PPI G2 and G3 to increase their lipophilicity. In the subsequent step, PPIs were conjugated to the alkylcarboxylate groups of alkylcarboxylate-PPI derivatives to increase the number of surface primary amines. Physicochemical properties of modified PPIs were determined. Transfection experiments (using both luciferase and green fluorescent protein (GFP)- expressing plasmids) and cytotoxicity assay were performed to evaluate the efficiency of the final derivatives. Results: Fabricated vectors condensed DNA effectively so that polyplexes with appropriate size (below 155 nm) and positive surface charge were constructed. Cross-linked low molecular weight PPIs (G2 or G3) with decanoate linkage increased transfection efficiency significantly while maintaining the low cytotoxicity. PPI G2 derivative exhibited increased buffering capacity which is believed to be responsible for better proton sponge mechanism leading to higher transfection efficiency. Conclusion: Our results indicated that oligomerization of low molecular weight PPI (PPI G2-alkyl-PPI G2 conjugate) could be an approach to increase the transfection efficiency and to lower the cytotoxicity of low molecular weight polycations. PMID:27872706

  16. Isolation of a very high molecular weight polylactosamine from an ovarian cyst mucin of blood group

    SciTech Connect

    Wu, A.S.S.; Bush, C.A.

    1986-05-01

    Treatment of a blood group A active ovarian cyst mucin glycoprotein with alkaline borohydride under conditions expected to cleave-O-glycosidically linked carbohydrate chains releases a polysaccharide of average molecular weight 25,000 daltons. It contains no peptide or mannose at the 1% level and carbohydrate analysis gives fuc:galNAc:gal:glcNAc in the ratio of 1:1:2.5:2.5. The /sup 13/C and /sup 1/H NMR spectra show that the polysaccharide has non-reducing terminal side chains of the structure galNAc(..cap alpha..-1 ..-->.. 3)(fuc(..cap alpha..-1 ..-->.. 2)) gal(..beta..-1 ..-->.. 3) glcNAc (i.e. a type 1 chain). Periodate oxidation removes all the fucose and galNAc from the non-reducing terminal but leaves intact the backbone composed of ..beta..-linked gal and glcNAc as would be expected for a polylactosamine. They conclude that this is a high molecular weight polylactosamine which is related to the asparagine linked polylactosamine chains of cell surface glycoproteins which have been implicated in cell differentiation. However, the blood group A polysaccharide from the ovarian cyst mucin is unique in several respects. It has a much larger molecular weight than even the erythroglycan of the red cell membrane protein, band 3, and is linked to the protein by an -O-glycosidic bond rather than the -N-asparagine linkage of the previously known polylactosamines which have a trimannosyl core. Its blood group A side chains are on a type one core rather than type 2 which is found on other polylactosamines.

  17. Low-molecular-weight heparin biosimilars: potential implications for clinical practice. Australian Low-Molecular-Weight Heparin Biosimilar Working Group (ALBW).

    PubMed

    Nandurkar, H; Chong, B; Salem, H; Gallus, A; Ferro, V; McKinnon, R

    2014-05-01

    A working group of clinicians and scientists was formed to review the clinical considerations for use of low-molecular-weight heparin (LMWH) biosimilars. LMWH are biological molecules of significant complexity; the full complexity of chemical structure is still to be elucidated. LMWH biosimilars are products that are biologically similar to their reference product and rely on clinical data from a reference product to establish safety and efficacy. The complex nature of LMWH molecules means that it is uncertain whether a LMWH biosimilar is chemically identical to its reference product; this introduces the possibility of differences in activity and immunogenicity. The challenge for regulators and clinicians is to evaluate the level of evidence required to demonstrate that a LMWH is sufficiently similar to the reference product. The consensus opinion of the working group is that prior to clinical use a LMWH biosimilar should have proven efficacy and safety, similar to the reference product with prospective studies, which should be confirmed with a proactive post-marketing pharmacovigilance programme.

  18. [High molecular weight chitosan and sodium alginate effect on secretory acid proteinase of Candida albicans].

    PubMed

    Calamari, Silvia; Bojanich, Alejandra; Barembaum, Silvina; Azcurra, Ana; Virga, Carolina; Dorronsoro, Susana

    2004-12-01

    The effect of high molecular weight chitosan (HMWCh) and sodium alginate (NaAL) on acid proteinase secretion of Candida albicans (one of culture collection and five isolates) was evaluated. The secretion of acid proteinase was induced in the presence and the absence of these polymers in different concentrations and their enzymatic activity was determined. HMWCh and NaAL significantly diminished the enzymatic activity (>76% for the collection strains and > 89% for the isolates, p < 0.05). HMWCh did not modify protein concentrations, but NaAL did. It can be concluded that both polymers can inhibit the proteinase activity of Candida albicans.

  19. An investigation of the preparation of high molecular weight perfluorocarbon polyethers

    NASA Technical Reports Server (NTRS)

    Watts, R. O.; Tarrant, P.

    1972-01-01

    High molecular weight perfluorocarbon polyether gums were obtained by photolysis of perfluorodienes and discyl fluorides containing a perfluorocarbon polyether backbond. The materials obtained are represented by chemical formulas. A method was developed whereby reactive acyl fluoride and trifluorovinyl end groups are converted into inert structures. In order to investigate the possible preparation of difunctional molecules which may be useful in polymer synthesis, the reactions of hexafluoropropene oxide (HFPO) with Grignard and organolithium reagents have been studied. Reactions of various nucleophilic reagents with HFPO were also investigated.

  20. Resolution of high molecular weight proteins in dependence on electric field strength in polyacrylamide gel electrophoresis.

    PubMed

    Starita-Geribaldi, M; Houri, A

    1997-01-01

    Resolution of high molecular weight proteins, in the upper region of polyacrylamide gels, was studied in relation to the type of electric field. Separations by constant field gel electrophoresis (CFGE) were compared to those in pulsed oscillatory high-performance electrophoresis (POPE), a novel technique which allows electrophoresis at high field strengths owing to a novel local field distribution. This distribution contributes to structural and mechanical stability of the gel with resultant well-reproducible separation, enhanced resolution, and higher absolute mobility of proteins in POPE.

  1. [Evaluation of molecular weights of hyaluronate preparations by multi-angle laser light scattering].

    PubMed

    Yomota, Chikako

    2003-01-01

    Hyaluronate (HA), a glycosaminoglycan polysaccharide, has been used for osteoarthritis, periartritis of the shoulder and rheumatoid arthritis by intraarticular administration, and in ophthalmic surgery such as anterior segment surgery, and eye lotion. In this study, the molecular weight (Mw) of HA preparations were estimated by size-exclusion chromatography (SEC) system consisted of a refractometer (RI) and a multi-angle laser light scattering (MALS). From the results, it has been clarified that a successful characterization of HA samples with Mw up to 2 - 3 x 10(6) g/mol was possible by multidetector system.

  2. O-acetylation of low-molecular-weight polysaccharide from Enteromorpha linza with antioxidant activity.

    PubMed

    Zhang, Zhongshan; Wang, Xiaomei; Zhao, Mingxing; Qi, Huimin

    2014-08-01

    Polysaccharide extracted from green algae Enteromorpha linza (EP) is a sulfated polysaccharide, which possesses excellent antioxidant activities. In present study, the acetylated derivatives of low-molecular-weight polysaccharide (LEP) was prepared with the method of response surface quadratic model. And then the antioxidant activities of the derivatives were investigated including scavenging effects of superoxide and hydroxyl radicals. The results of chemical analysis and FT-IR spectrum showed the acetylation was successful. And in addition, certain derivative with different degree of substitution (DS) exhibited different antioxidant activity.

  3. Low Molecular Weight Heparin Induced Skin Necrosis without Platelet Fall Revealing Immunoallergic Heparin Induced Thrombocytopenia

    PubMed Central

    Godet, Thomas; Perbet, Sébastien; Lebreton, Aurélien; Gayraud, Guillaume; Cayot, Sophie; Tremblay, Aymeric; Ravinet, Aurélie; Christophe, Sébastien; Guérin, Renaud; Pascal, Julien; Jabaudon, Matthieu; Hassan, Amr; Sapin, Anne-Françoise; Bazin, Jean-Etienne; Constantin, Jean-Michel

    2013-01-01

    Low molecular weight heparins (LMWH) are commonly used in the ICU setting for thromboprophylaxis as well as curative decoagulation as required during renal replacement therapy (RRT). A rare adverse event revealing immunoallergic LMWH induced thrombopenia (HIT) is skin necrosis at injection sites. We report the case of a patient presenting with skin necrosis witnessing an HIT after RRT, without thrombocytopenia. The mechanism remains unclear. Anti-PF4/heparin antibodies, functional tests (HIPA and/or SRA), and skin biopsy are of great help to evaluate differential diagnosis with a low pretest probability 4T's score. PMID:24307958

  4. Synthesis and kinetic studies of a low-molecular weight organocatalyst for phosphate hydrolysis in water.

    PubMed

    Merschky, Michael; Schmuck, Carsten

    2009-12-07

    Kinetic studies of a low-molecular weight organocatalyst 1 are presented. Compound 1 contains two histidines and one cationic side chain attached to a central aromatic core. In aqueous solution 1 accelerates the hydrolysis of a prototypal phosphodiester with rate enhancements of up to two orders of magnitude. A detailed HPLC analysis of hydrolysis experiments in Bis-Tris-buffer showed that the buffer itself can act as a nucleophile at least with the cyclic phosphate 16. Compound 1 is also an efficient host for the binding of bis-(para-nitrophenyl)-phosphate 14 with extraordinary high affinity of K(ass) = 24,400 M(-1) in buffered water.

  5. Surfactant-enhanced biodegradation of high molecular weight polycyclic aromatic hydrocarbons by stenotrophomonas maltophilia

    PubMed

    Boonchan; Britz; Stanley

    1998-08-20

    The objectives of this study were to isolate and evaluate microorganisms with the ability to degrade high molecular weight polycyclic aromatic hydrocarbons (PAHs) in the presence of synthetic surfactants. Stenotrophomonas maltophilia VUN 10,010, isolated from PAH-contaminated soil, utilized pyrene as a sole carbon and energy source and also degraded other high molecular weight PAHs containing up to seven benzene rings. Various synthetic surfactants were tested for their ability to improve the PAH degradation rate of strain VUN 10,010. Anionic and cationic surfactants were highly toxic to this strain, and the Tween series was used as a growth substrate. Five nonionic surfactants (Brij 35, Igepal CA-630, Triton X-100, Tergitol NP-10, and Tyloxapol) were not utilized by, and were less toxic to, strain VUN 10,010. MSR and log Km values were determined for fluoranthene, pyrene, and benzo[a]pyrene in the presence of these nonionic surfactants and their apparent solubility was increased by a minimum of 250-fold in the presence of 10 g L-1 of all surfactants. The rate of pyrene degradation by strain VUN 10,010 was enhanced by the addition of four of the nonionic surfactants (5-10 g L-1); however, 5 g L-1 Igepal CA-630 inhibited pyrene degradation and microbial growth. The specific growth rate of VUN 10,010 on pyrene was increased by 67% in the presence of 10 g L-1 Brij 35 or Tergitol NP-10. The addition of Brij 35 and Tergitol NP-10 to media containing a single high molecular weight PAH (four and five benzene rings) as the sole carbon source increased the maximum specific PAH degradation rate and decreased the lag period normally seen for PAH degradation. The addition of Tergitol NP-10 to VUN 10,010 cultures which contained a PAH mixture (three to seven benzene rings) substantially improved the overall degradation rate of each PAH and increased the specific growth rate of VUN 10,010 by 30%. Evaluation of the use of VUN 10,010 for degrading high molecular weight PAHs in

  6. Total internal reflection ellipsometry and SPR detection of low molecular weight environmental toxins

    NASA Astrophysics Data System (ADS)

    Nabok, A. V.; Tsargorodskaya, A.; Hassan, A. K.; Starodub, N. F.

    2005-06-01

    The environmental toxins, such as herbicides simazine and atrazine, and T2 mycotoxin were registered with the optical methods of surface plasmon resonance (SPR) and recently developed total internal reflection ellipsometry (TIRE). The immune assay approach was exploited for in situ registration of the above low molecular weight toxins with specific antibodies immobilised onto the gold surface via (poly)allylamine hydrochloride layer using electrostatic self-assembly (ESA) technique. The comparison of two methods of SPR and TIRE shows a higher sensitivity of the latter.

  7. Molecular weight control in organochromium olefin polymerization catalysis by hemilabile ligand–metal interactions

    PubMed Central

    Mark, Stefan; Wadepohl, Hubert

    2016-01-01

    Summary A series of Cr(III) complexes based on quinoline-cyclopentadienyl ligands with additional hemilabile side arms were prepared and used as single-site catalyst precursors for ethylene polymerization. The additional donor functions interact with the metal centers only after activation with the co-catalyst. Evidence for this comes from DFT-calculations and from the differing behavior of the complexes in ethylene polymerization. All complexes investigated show very high catalytic activity and the additional side arm minimizes chain-transfer reactions, leading to increase of molecular weights of the resulting polymers. PMID:27559387

  8. Effect of irradiation on crystallinity and mechanical properties of ultrahigh molecular weight polyethylene

    SciTech Connect

    Zhao, Yong; Luo, Yunxia; Jiang, Bingzheng . Changchun Inst. of Applied Chemistry)

    1993-12-10

    Ultrahigh molecular weight polyethylene (UHMWPE) has been irradiated (0--40 Mrad) with a Co[sup 60] source at room temperature under vacuum. The crystallinity has been investigated by differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS). The mechanical properties have been determined at room temperature. A significant increase of heat of fusion can be seen at low irradiation doses, which is attributed to crystallization, caused by chain scission during the process of irradiation. It is also observed that the thickness of the lamellae changes with irradiation dose. The Young's modulus has been improved significantly after irradiation at low doses.

  9. [Venous thrombo-embolic disease in cancer. Low molecular weight heparin indications].

    PubMed

    Nou, M; Laroche, J-P

    2016-05-01

    Cancer and venous thrombo-embolic disease (VTE) are closely related. Indeed, cancer can reveal VTE and VTE can be the first sign of cancer. Low molecular weight heparin (LWMH) is now the first line treatment in cancer patients. Compliance with marketing authorizations and guidelines are crucial for patient-centered decision-making. This work deals with the prescription of LWMH in patients who develop VTE during cancer in order to better recognize what should or should not be done. The patient's wishes must be taken into consideration when making the final therapeutic decision. The other treatments are discussed: vitamin K antagonists and direct oral anticoagulants (DOACs) may be useful.

  10. Low molecular weight phenols from the bioactive aqueous fraction of Cestrum parqui.

    PubMed

    D'Abrosca, Brigida; DellaGreca, Marina; Fiorentino, Antonio; Monaco, Pietro; Zarrelli, Armando

    2004-06-30

    The aqueous fraction of fresh leaves of Cestrum parqui and its organic fractions have been assayed for their phytotoxicity on Lactuca sativa, Lycopersicon esculentum, and Allium cepa. The tests showed that the bioactivity was retained in the organic fractions. Chromatographic processes led to isolation and characterization of the N-(p-carboxymethylphenyl)-p-hydroxybenzamide together with 17 low molecular weight phenols and 2 flavones. The phytotoxicity tests showed a good activity of these compounds on the target species. Comparison of some metabolites with commercial herbicides revealed a major activity of the natural compounds at lower concentrations.

  11. Determination of molecular weight of heparin by size exclusion chromatography with universal calibration.

    PubMed

    Guo, X; Condra, M; Kimura, K; Berth, G; Dautzenberg, H; Dubin, P L

    2003-01-01

    The molecular weight (MW) of heparin can be accurately determined by size exclusion chromatography using "universal calibration." A universal calibration curve was constructed for Superose 12 with standard pullulan samples and verified using characterized ficoll fractions. This calibration yielded the correct MW of heparin as determined by light scattering, when the ionic strength of the mobile phase was maintained over 1.0M. Sodium poly(styrenesulfonate) samples were not suitable standards because of adsorption at high salt concentration and repulsion from the packing material at low ionic strength. The extraordinarily high charge density of heparin leads to the need for high salt concentration to screen such repulsions.

  12. Preparation of high molecular weight gDNA and bacterial artificial chromosome (BAC) libraries in plants.

    PubMed

    Biradar, Siddanagouda S; Nie, Xiaojun; Feng, Kewei; Weining, Song

    2014-01-01

    Bacterial artificial chromosome (BAC) libraries are extremely valuable large-insert DNA libraries for physical mapping, positional cloning, comparative genomic analysis, complete genome sequencing, and evolutionary studies. Due to their stability and relative simplicity BAC libraries are most preferred over other approaches for cloning large genomic DNA fragments for large-insert libraries. Isolation of intact high molecular weight (HMW) DNA is a critical step underlying the success of large-insert genomic DNA library construction. It requires the isolation of purified nuclei, embedding them into LMP agarose plugs, restriction digestion of the plugs, and quite often size selection using PFGE and electro-elution of insert DNA. The construction of BAC libraries is complex and challenging for most molecular laboratories. To facilitate the construction of BAC libraries, we present a step-by-step protocol for isolation of HMW DNA and construction of plant BAC libraries.

  13. Detection of high molecular weight proteins by MALDI imaging mass spectrometry.

    PubMed

    Mainini, Veronica; Bovo, Giorgio; Chinello, Clizia; Gianazza, Erica; Grasso, Marco; Cattoretti, Giorgio; Magni, Fulvio

    2013-06-01

    MALDI imaging mass spectrometry (IMS) is a unique technology to explore the spatial distribution of biomolecules directly on tissues. It allows the in situ investigation of a large number of small proteins and peptides. Detection of high molecular weight proteins through MALDI IMS still represents an important challenge, as it would allow the direct investigation of the distribution of more proteins involved in biological processes, such as cytokines, enzymes, neuropeptide precursors and receptors. In this work we compare the traditional method performed with sinapinic acid with a comparable protocol using ferulic acid as the matrix. Data show a remarkable increase of signal acquisition in the mass range of 20k to 150k Th. Moreover, we report molecular images of biomolecules above 70k Th, demonstrating the possibility of expanding the application of this technology both in clinical investigations and basic science.

  14. Bio-Based Bisfuran: Synthesis, Crystal Structure and Low Molecular Weight Amorphous Polyester.

    PubMed

    Gaitonde, Vishwanath; Lee, Kyunghee; Kirschbaum, Kristin; Sucheck, Steven J

    2014-07-23

    Discovery of renewable monomer feedstocks for fabrication of polymeric demand is critical in achieving sustainable materials. In the present work we have synthesized bisfuran diol (BFD) monomer from furfural, over four steps. BFD was examined via X-ray crystallography to understand the molecular arrangement in space, hydrogen bonding and packing of the molecules. This data was further used to compare BFD with structurally related Bisphenol A (BPA), and its known derivatives to predict the potential estrogenic or anti-estrogenic activities in BFD. Further, BFD was reacted with succinic acid to generate polyester material, bisfuran polyester (BFPE-1). MALDI characterization of BFPE-1 indicates low molecular weight polyester and thermal analysis reveals amorphous nature of the material.

  15. Weighted Distance Functions Improve Analysis of High-Dimensional Data: Application to Molecular Dynamics Simulations.

    PubMed

    Blöchliger, Nicolas; Caflisch, Amedeo; Vitalis, Andreas

    2015-11-10

    Data mining techniques depend strongly on how the data are represented and how distance between samples is measured. High-dimensional data often contain a large number of irrelevant dimensions (features) for a given query. These features act as noise and obfuscate relevant information. Unsupervised approaches to mine such data require distance measures that can account for feature relevance. Molecular dynamics simulations produce high-dimensional data sets describing molecules observed in time. Here, we propose to globally or locally weight simulation features based on effective rates. This emphasizes, in a data-driven manner, slow degrees of freedom that often report on the metastable states sampled by the molecular system. We couple this idea to several unsupervised learning protocols. Our approach unmasks slow side chain dynamics within the native state of a miniprotein and reveals additional metastable conformations of a protein. The approach can be combined with most algorithms for clustering or dimensionality reduction.

  16. Fluorophore-assisted carbohydrate electrophoresis for the determination of molecular mass of heparins and low-molecular-weight (LMW) heparins.

    PubMed

    Buzzega, Dania; Maccari, Francesca; Volpi, Nicola

    2008-11-01

    We report the use of fluorophore-assisted carbohydrate electrophoresis (FACE) to determine the molecular mass (M) values of heparins (Heps) and low-molecular-weight (LMW)-Hep derivatives. Hep are labeled with 8-aminonaphthalene-1,3,6-trisulfonic acid and FACE is able to resolve each fraction as a discrete band depending on their M. After densitometric acquisition, the migration distance of each Hep standard is acquired and the third-grade polynomial calibration standard curve is determined by plotting the logarithms of the M values as a function of migration ratio. Purified Hep samples having different properties, pharmaceutical Heps and various LMW-Heps were analyzed by both FACE and conventional high-performance size-exclusion liquid chromatography (HPSEC) methods. The molecular weight value on the top of the chromatographic peak (Mp), the number-average Mn, weight-average Mw and polydispersity (Mw/Mn) were examined by both techniques and found to be similar. This approach offers certain advantages over the HPSEC method. The derivatization process with 8-aminonaphthalene-1,3,6-trisulfonic acid is complete after 4 h so that many samples may be analyzed in a day also considering that multiple samples can be run simultaneously and in parallel and that a single FACE analysis requires approx. 15 min. Furthermore, FACE is a very sensitive method as it requires approx. 5-10 microg of Heps, about 10-100-fold lower than samples and standards used in HPSEC evaluation. Finally, the utilization of mini-gels allows the use of very low amounts of reagents with neither expensive equipment nor any complicated procedures having to be applied. This study demonstrates that FACE analysis is a sensitive method for the determination of the M values of Heps and LMW-Heps with possible utilization in virtually any kind of research and development such as quality control laboratories due to its rapid, parallel analysis of multiple samples by means of common and simple largely used

  17. Neuraminidase inhibitor R-125489 - A promising drug for treating influenza virus: Steered molecular dynamics approach

    SciTech Connect

    Mai, Binh Khanh; Li, Mai Suan

    2011-07-08

    Highlights: {yields} We study binding affinity of R-125489 and its prodrug CS-8958 to neuraminidase of pathogenic influenza viruses by molecular dynamics simulations. {yields} It is shown that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. {yields} We predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus. {yields} The high correlation between theoretical and experimental data implies that SMD is a very promising tool for drug design. -- Abstract: Two neuraminidase inhibitors, oseltamivir and zanamivir, are important drug treatments for influenza. Oseltamivir-resistant mutants of the influenza virus A/H1N1 and A/H5N1 have emerged, necessitating the development of new long-acting antiviral agents. One such agent is a new neuraminidase inhibitor R-125489 and its prodrug CS-8958. An atomic level understanding of the nature of this antiviral agents binding is still missing. We address this gap in our knowledge by applying steered molecular dynamics (SMD) simulations to different subtypes of seasonal and highly pathogenic influenza viruses. We show that, in agreement with experiments, R-125489 binds to neuraminidase more tightly than CS-8958. Based on results obtained by SMD and the molecular mechanics-Poisson-Boltzmann surface area method, we predict that R-125489 can be used to treat not only wild-type but also tamiflu-resistant N294S, H274Y variants of A/H5N1 virus as its binding affinity does not vary much across these systems. The high correlation level between theoretically determined rupture forces and experimental data on binding energies for the large number of systems studied here implies that SMD is a promising tool for drug design.

  18. Discovery of non-competitive thrombin inhibitor derived from competitive tryptase inhibitor skeleton: Shift in molecular recognition resulted from skeletal conversion of carboxylate into phosphonate.

    PubMed

    Aoyama, Hiroshi; Ijuin, Ryosuke; Kato, Jun-ya; Urushiyama, Sarasa; Tetsuhashi, Masashi; Hashimoto, Yuichi; Yokomatsu, Tsutomu

    2015-09-01

    A novel series of terminal and internal phosphonate esters based on our previously developed aryl carboxylate-type tryptase selective inhibitor 1 was synthesized. The potency of these synthesized compounds was assessed in vitro with an enzyme inhibition assay using three available serine proteases, that is, tryptase, trypsin, and thrombin. The internal phosphonate derivative 6 showed potent thrombin inhibitory activity with an IC50 value of 1.0 μM, whereas it exhibited no or only weak tryptase and trypsin inhibition at 10 μM. The Lineweaver-Burk plot analysis indicates that the inhibition pattern of thrombin with 6 is non-competitive in spite of the fact that the lead carboxylate compound 1 is competitive inhibitor. Therefore, the skeletal conversion of the carboxylate into a phosphonate alters the mode of molecular recognition of these inhibitors by thrombin.

  19. Influence of galactomannans with different molecular weights on the gelation of whey proteins at neutral pH.

    PubMed

    Monteiro, Sónia R; Tavares, Cláudia; Evtuguin, Dmitry V; Moreno, Nuno; Lopes da Silva, J A

    2005-01-01

    The effect of locust bean gum, a galactomannan, with different molecular weights on the microstructure and viscoelastic properties of heat-induced whey protein gels has been studied using confocal laser scanning microscopy and small-deformation rheology. The results obtained clearly showed that differences in the molecular weight of the polysaccharide have a significant influence on the gel microstructure. Homogeneous mixtures and phase-separated systems, with dispersed droplet and bicontinuous morphologies, were observed by changing the polysaccharide/protein ratio and/or the molecular weight. At 11% whey protein, below the gelation threshold of the protein alone, the presence of the nongelling polysaccharide induces gelation to occur. At higher protein concentration, the main effect of the polysaccharide was a re-enforcement of the gel. However, at the higher molecular weight and concentration of the nongelling polymer, the protein network starts to lose elastic perfection, probably due to the formation of bicontinuous structures with lower connectivity.

  20. The polysaccharide and low molecular weight components of Opuntia ficus indica cladodes: Structure and skin repairing properties.

    PubMed

    Di Lorenzo, Flaviana; Silipo, Alba; Molinaro, Antonio; Parrilli, Michelangelo; Schiraldi, Chiara; D'Agostino, Antonella; Izzo, Elisabetta; Rizza, Luisa; Bonina, Andrea; Bonina, Francesco; Lanzetta, Rosa

    2017-02-10

    The Opuntia ficus-indica multiple properties are reflected in the increasing interest of chemists in the identification of its natural components having pharmaceutical and/or cosmetical applications. Here we report the structural elucidation of Opuntia ficus-indica mucilage that highlighted the presence of components differing for their chemical nature and the molecular weight distribution. The high molecular weight components were identified as a linear galactan polymer and a highly branched xyloarabinan. The low molecular weight components were identified as lactic acid, D-mannitol, piscidic, eucomic and 2-hydroxy-4-(4'-hydroxyphenyl)-butanoic acids. A wound healing assay was performed in order to test the cicatrizing properties of the various components, highlighting the ability of these latter to fasten dermal regeneration using a simplified in vitro cellular model based on a scratched keratinocytes monolayer. The results showed that the whole Opuntia mucilage and the low molecular weight components are active in the wound repair.

  1. Effects of the Terminal Structure, Purity, and Molecular Weight of an Amorphous Conjugated Polymer on Its Photovoltaic Characteristics.

    PubMed

    Kuwabara, Junpei; Yasuda, Takeshi; Takase, Naoto; Kanbara, Takaki

    2016-01-27

    The photovoltaic characteristics of an amorphous polymer containing EDOT and fluorene units were investigated. In particular, the effects of the terminal structure, residual amount of Pd, and molecular weight were systematically investigated. Direct arylation polycondensation of EDOT followed by an established purification method readily afforded polymers with different terminal structures, Pd contents, and molecular weights. Of these factors, the terminal structure of the polymer was a crucial factor affecting the photovoltaic characteristics. For example, the polymer with a Br terminal had a PCE of 2.9% in bulk-heterojunction organic photovoltaics (BHJ OPVs) with a fullerene derivative, whereas the polymer without a Br terminal had a PCE of 4.6% in the same cell configuration. The decreased Pd residues and high molecular weights of the polymers increased the long-term stability of the devices. Moreover, BHJ OPVs containing the high-molecular-weight polymer could be fabricated with an environmentally friendly nonhalogenated solvent.

  2. Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation.

    PubMed

    Pandey, Rajan Kumar; Kumbhar, Bajarang Vasant; Srivastava, Shubham; Malik, Ruchi; Sundar, Shyam; Kunwar, Ambarish; Prajapati, Vijay Kumar

    2017-01-01

    Visceral leishmaniasis affects people from 70 countries worldwide, mostly from Indian, African and south American continent. The increasing resistance to antimonial, miltefosine and frequent toxicity of amphotericin B drives an urgent need to develop an antileishmanial drug with excellent efficacy and safety profile. In this study we have docked series of febrifugine analogues (n = 8813) against trypanothione reductase in three sequential docking modes. Extra precision docking resulted into 108 ligands showing better docking score as compared to two reference ligand. Furthermore, 108 febrifugine analogues and reference inhibitor clomipramine were subjected to ADMET, QikProp and molecular mechanics, the generalized born model and solvent accessibility study to ensure the toxicity caused by compounds and binding-free energy, respectively. Two best ligands (FFG7 and FFG2) qualifying above screening parameters were further subjected to molecular dynamics simulation. Conducting these studies, here we confirmed that 6-chloro-3-[3-(3-hydroxy-2-piperidyl)-2-oxo-propyl]-7-(4-pyridyl) quinazolin-4-one can be potential drug candidate to fight against Leishmania donovani parasites.

  3. A structure-activity relationship study of catechol- O-methyltransferase inhibitors combining molecular docking and 3D QSAR methods

    NASA Astrophysics Data System (ADS)

    Tervo, Anu J.; Nyrönen, Tommi H.; Rönkkö, Toni; Poso, Antti

    2003-12-01

    A panel of 92 catechol- O-methyltransferase (COMT) inhibitors was used to examine the molecular interactions affecting their biological activity. COMT inhibitors are used as therapeutic agents in the treatment of Parkinson's disease, but there are limitations in the currently marketed compounds due to adverse side effects. This study combined molecular docking methods with three-dimensional structure-activity relationships (3D QSAR) to analyse possible interactions between COMT and its inhibitors, and to incite the design of new inhibitors. Comparative molecular field analysis (CoMFA) and GRID/GOLPE models were made by using bioactive conformations from docking experiments, which yielded q2 values of 0.594 and 0.636, respectively. The docking results, the COMT X-ray structure, and the 3D QSAR models are in agreement with each other. The models suggest that an interaction between the inhibitor's catechol oxygens and the Mg2+ ion in the COMT active site is important. Both hydrogen bonding with Lys144, Asn170 and Glu199, and hydrophobic contacts with Trp38, Pro174 and Leu198 influence inhibitor binding. Docking suggests that a large R1 substituent of the catechol ring can form hydrophobic contacts with side chains of Val173, Leu198, Met201 and Val203 on the COMT surface. Our models propose that increasing steric volume of e.g. the diethylamine tail of entacapone is favourable for COMT inhibitory activity.

  4. High Molecular Weight Typing with MALDI-TOF MS - A Novel Method for Rapid Typing of Clostridium difficile.

    PubMed

    Rizzardi, Kristina; Åkerlund, Thomas

    2015-01-01

    Clostridium difficile strains were typed by a newly developed MALDI-TOF method, high molecular weight typing, and compared to PCR ribotyping. Among 500 isolates representing 59 PCR ribotypes a total of 35 high molecular weight types could be resolved. Although less discriminatory than PCR ribotyping, the method is extremely fast and simple, and supports for cost-effective screening of isolates during outbreak situations.

  5. A New Class of Molecular Targeted Radioprotectors: GSK-3beta Inhibitors

    SciTech Connect

    Thotala, Dinesh K.; Geng Ling; Dickey, Amy K.; Hallahan, Dennis E.; Yazlovitskaya, Eugenia M.

    2010-02-01

    Purpose: Development of new treatments is critical to effective protection against radiation-induced injury. We investigate the potential of developing small-molecule inhibitors of glycogen synthase kinase 3beta (GSK-3beta)-SB216763 or SB415286-as radioprotective agents to attenuate intestinal injury. Methods and Materials: A survival study was done by use of C57BL/6J mice to evaluate the radioprotective effect of GSK-3beta inhibitors. Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay and immunohistochemical staining for Bax and Bcl-2 were used to assess apoptosis in the small intestines of the treated mice. A clonogenic survival study, apoptosis assays (staining with annexin V or 4',6-diamidino-2-phenylindole), and immunoblot analysis of beta-catenin, Bcl-2, Bax, and caspase 3 were done by use of Rat intestinal epithelial cell line IEC-6 cells. Results: Pretreatment with SB415286 significantly improved survival of mice irradiated with 8 and 12 Gy. Mice pretreated with SB216763 or SB415286 showed a significant reduction in TUNEL- and Bax-positive cells and an increase in Bcl-2-positive cells in intestinal crypts at 4 and/or 12 h after radiation with 4 and/or 8 Gy compared with radiation alone. Pretreatment of irradiated IEC-6 cells with GSK-3beta inhibitors significantly increased clonogenic survival compared with cells treated with radiation alone. This increase was due to the attenuation of radiation-induced apoptosis, as shown by annexin V and 4',6-diamidino-2-phenylindole assays, as well as immunoblot analysis of Bcl-2, Bax, and caspase 3. Conclusions: Glycogen synthase kinase 3beta small-molecule inhibitors protect mouse intestine from radiation-induced damage in cell culture and in vivo and improve survival of mice. Molecular mechanisms of this protection involve attenuated radiation-induced apoptosis regulated by Bcl-2, Bax, and caspase 3. Therefore GSK-3beta inhibitors reduce deleterious consequences of intestinal irradiation and

  6. Supplementation with a new trypsin inhibitor from peanut is associated with reduced fasting glucose, weight control, and increased plasma CCK secretion in an animal model.

    PubMed

    Serquiz, Alexandre C; Machado, Richele J A; Serquiz, Raphael P; Lima, Vanessa C O; de Carvalho, Fabiana Maria C; Carneiro, Marcella A A; Maciel, Bruna L L; Uchôa, Adriana F; Santos, Elizeu A; Morais, Ana H A

    2016-12-01

    Ingestion of peanuts may have a beneficial effect on weight control, possibly due to the satietogenic action of trypsin inhibitors. The aim of this study was to isolate a new trypsin inhibitor in a typical Brazilian peanut sweet (paçoca) and evaluate its effect in biochemical parameters, weight gain and food intake in male Wistar rats. The trypsin inhibitor in peanut paçoca (AHTI) was isolated. Experimental diets were prepared with AIN-93G supplemented with AHTI. Animals had their weight and food intake monitored. Animals were anesthetized, euthanized, and their bloods collected by cardiac puncture for dosage of cholecystokinin (CCK) and other biochemical parameters. Supplementation with AHTI significantly decreased fasting glucose, body weight gain, and food intake. These effects may be attributed to increased satiety, once supplemented animals showed no evidence of impaired nutritional status and also because AHTI increased CCK production. Thus, our results indicate that AHTI, besides reducing fasting glucose, can reduce weight gain via food intake reduction.

  7. Heat-mediated, ultra-rapid electrophoretic transfer of high and low molecular weight proteins to nitrocellulose membranes.

    PubMed

    Kurien, Biji T; Scofield, R Hal

    2002-08-01

    Here, we report an ultra-rapid method for the transfer of high and low molecular weight proteins to nitrocellulose membranes following sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In this procedure, the electro-transfer was performed with heated (70-75 degrees C) normal transfer buffer from which methanol had been omitted. Complete transfer of high and low molecular weight proteins (a purified protein, molecular weight protein standards and proteins from a human tissue extract) could be carried out in 10 min for a 0.75-mm, 7% SDS-PAGE gel. For 10% and 12.5% gels (0.75 mm), the corresponding time was 15 min. In the case of 1.5-mm gels, a complete transfer could be carried out in 20 min for 7%, 10% and 12.5% gels. The permeability of the gel is increased by heat, such that the proteins trapped in the polyacrylamide gel matrix can be easily transferred to the membrane. When the heat-mediated transfer method was compared with a conventional transfer protocol, under similar conditions, we found that the latter method transferred minimal low molecular weight proteins while retaining most of the high molecular weight proteins in the gel. In summary, this procedure is very rapid, avoids the use of methanol and is particularly useful for the transfer of high molecular weight proteins.

  8. Effects of Molecular Weight upon Irradiation-Cross-Linked Poly(vinyl alcohol)/Clay Aerogel Properties.

    PubMed

    Chen, Hong-Bing; Zhao, Yan; Shen, Peng; Wang, Jun-Sheng; Huang, Wei; Schiraldi, David A

    2015-09-16

    Facile fabrication of mechanically strong poly(vinyl alcohol) (PVOH)/clay aerogel composites through a combination of increasing polymer molecular weights and gamma irradiation-cross-linking is reported herein. The aerogels produced from high polymer molecular weights exhibit significantly increased compressive moduli, similar to the effect of irradiation-induced cross-linking. The required irradiation dose for fabricating strong PVOH composite aerogels with dense microstructure decreased with increasing polymer molecular weight. Neither thermal stability nor flammability was significantly changed by altering the polymer molecular weight or by modest gamma irradiation, but they were highly dependent upon the polymer/clay ratio in the aerogel. Optimization of the mechanical, thermal, and flammability properties of these composite aerogels could therefore be obtained by using relatively low levels of polymer, with very high polymer molecular weight, or lower molecular weight coupled with moderate gamma irradiation. The facile preparation of strong, low flammability aerogels is an alternative to traditional polymer foams in applications where fire safety is important.

  9. Weak oligomerization of low-molecular-weight protein tyrosine phosphatase is conserved from mammals to bacteria.

    PubMed

    Blobel, Jascha; Bernadó, Pau; Xu, Huimin; Jin, Changwen; Pons, Miquel

    2009-08-01

    The well-characterized self-association of a mammalian low-molecular-weight protein tyrosine phosphatase (lmwPTP) produces inactive oligomers that are in equilibrium with active monomers. A role of the inactive oligomers as supramolecular proenzymes has been suggested. The oligomerization equilibrium of YwlE, a lmwPTP from Bacillus subtilis, was studied by NMR. Chemical shift data and NMR relaxation confirm that dimerization takes place through the enzyme's active site, and is fully equivalent to the dimerization previously characterized in a eukaryotic low-molecular-weight phosphatase, with similarly large dissociation constants. The similarity between the oligomerization of prokaryotic and eukaryotic phosphatases extends beyond the dimer and involves higher order oligomers detected by NMR relaxation analysis at high protein concentrations. The conservation across different kingdoms of life suggests a physiological role for lmwPTP oligomerization in spite of the weak association observed in vitro. Structural data suggest that substrate modulation of the oligomerization equilibrium could be a regulatory mechanism leading to the generation of signaling pulses. The presence of a phenylalanine residue in the dimerization site of YwlE, replacing a tyrosine residue conserved in all eukaryotic lmwPTPs, demonstrates that lmwPTP regulation by oligomerization can be independent from tyrosine phosphorylation.

  10. X-ray Photon Correlation Spectroscopy on polymer films with Molecular Weight Dependence

    NASA Astrophysics Data System (ADS)

    Kim, Hyunjung; Ruehm, A.; Lurio, L. B.; Basu, J. K.; Lal, J.; Sinha, S. K.; Mochrie, S. G. J.

    2002-03-01

    We have applied x-ray photon correlation spectroscopy (XPCS) to study the dynamics of surface fluctuations in thin supported polystyrene films as a function of wave vector, temperature, film thickness, and molecular weight. Molecular weights, ranging from 30× 10^3 to 650 × 10^3, were used in the study. Lateral length scales probed are at least ten times smaller than those accessible in conventional dynamic light scattering. Good agreement between the experimental results and conventional theory permits us to determine the film viscosity. The comparison between the values of the viscosity obtained from these data with those of bulk PS will be discussed. footnote Work at MIT and Yale was supported by the NSF (DMR 0071755). 8-ID is supported by the DOE Facilities Initiative Program DE-FG02-96ER45593 and NSERC. The APS is supported by the U.S. Department of Energy, Office of Basic Science, under Contract No. W-31-109-ENG-38.

  11. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk

    PubMed Central

    Cheema, M.; Mohan, M. S.; Campagna, S. R.; Jurat-Fuentes, J. L.; Harte, F. M.

    2015-01-01

    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk. PMID:26074238

  12. Extraction conditions of Antheraea mylitta sericin with high yields and minimum molecular weight degradation.

    PubMed

    Yun, Haesung; Oh, Hanjin; Kim, Moo Kon; Kwak, Hyo Won; Lee, Jeong Yun; Um, In Chul; Vootla, Shyam Kumar; Lee, Ki Hoon

    2013-01-01

    Although the technique for extracting the Bombyx mori sericin has been extensively known, the extraction of sericin from wild-silkworm cocoons is not yet standardized. The aim of this study was to find the optimal conditions for the extraction of sericin from Antheraea mylitta cocoons, with high yields and minimum degradation. We attempted to apply various protocols for the extraction of the A. mylitta sericin (AmS). Among these, we found that the extraction of AmS with a sodium carbonate solution exhibited the highest yield except the conventional soap-alkali extraction. To find the optimal conditions for the AmS extraction with the sodium carbonate, we changed the concentration of sodium carbonate and the treatment time. With an increase in the sodium carbonate concentration and the extraction time, the yield of AmS increased, but the molecular weight (MW) of AmS decreased. Considering the yield, molecular weight distribution (MWD) and amino acid composition of AmS, we suggest that the optimal conditions for the AmS extraction require treatment with 0.02 M sodium carbonate and boiling for 60 min.

  13. Influence of the Molecular Weight and Charge of Antibiotics on Their Release Kinetics From Gelatin Nanospheres.

    PubMed

    Song, Jiankang; Odekerken, Jim C E; Löwik, Dennis W P M; López-Pérez, Paula M; Welting, Tim J M; Yang, Fang; Jansen, John A; Leeuwenburgh, Sander C G

    2015-07-01

    In this study, we investigated the fundamental relationship between the physicochemical characteristics of antibiotics and the kinetics of their release from gelatin nanospheres. We observed that antibiotics of high molecular weight (colistin and vancomycin) were released in a sustained manner from oppositely charged gelatin carriers for more than 14 d, as opposed to antibiotics of low molecular weight (gentamicin and moxifloxacin) which were released in a burst-like manner. The release kinetics of positively charged colistin strongly correlated with the rate of the enzymatic degradation of gelatin. To elucidate the differences among release kinetics of antibiotics, we explored the mechanism of interactions between antibiotics and gelatin nanospheres by monitoring the kinetics of release of antibiotics as a function of pH, ionic strength, and detergent concentrations. These studies revealed that the interactions between antibiotics and gelatin nanospheres were mainly dominated by (i) strong electrostatic forces for colistin; (ii) strong hydrophobic and electrostatic forces for vancomycin; (iii) weak electrostatic and hydrophobic forces for gentamicin; and (iv) weak hydrophobic forces for moxifloxacin. These results confirm that release of antibiotics from gelatin nanospheres strongly depends on the physicochemical characteristics of the antibiotics.

  14. Efficient biodegradation of high-molecular-weight polyethylene glycols by pure cultures of Pseudomonas stutzeri.

    PubMed Central

    Obradors, N; Aguilar, J

    1991-01-01

    Biodegradation of polyethylene glycols (PEGs) of up to 13,000 to 14,000 molecular weight has been shown to be performed by a river water bacterial isolate (strain JA1001) identified as Pseudomonas stutzeri. A pure culture of strain JA1001 grew on PEG 1000 or PEG 10000 at 0.2% (wt/vol) as a sole source of carbon and energy with a doubling time of 135 or 150 min, respectively. Cultures metabolized 2 g of polymer per liter in less than 24 h and 10 g/liter in less than 72 h. The limit of 13,500 molecular weight in the size of the PEG sustaining growth and the presence of a PEG-oxidative activity in the periplasmic space indicated that PEGs cross the outer membrane and are subsequently metabolized in the periplasm. PEG oxidation was found to be catalyzed by PEG dehydrogenase, an enzyme that has been shown to be a single polypeptide. Characterization of PEG dehydrogenase revealed glyoxylic acid as the product of the PEG-oxidative cleavage. Glyoxylate supported growth by entering the cell and introducing its carbons in the general metabolism via the dicarboxylic acid cycle, as indicated by the ability of strain JA1001 to grow on this compound and the presence of malate synthase, the first enzyme in the pathway, in extracts of PEG-grown cells. Images PMID:1768106

  15. Relationship of molecular weight distribution profile of unreduced gluten protein extracts with quality characteristics of bread.

    PubMed

    Chaudhary, Nisha; Dangi, Priya; Khatkar, B S

    2016-11-01

    A statistical correlation was established among the molecular weight distribution patterns of unreduced gluten proteins and physicochemical, rheological and bread-making quality characteristics of wheat varieties. Size exclusion chromatography fractionated the gluten proteins apparently into five peaks. Peak I signified glutenins (30-130kDa), peak II as gliadins (20-55kDa), peak III as very low molecular weight monomeric gliadins (10-28kDa), peak IV and V, collectively, as albumins and globulins (<10kDa). Peaks I and II had appreciable effects on dough development time (r=0.830(∗∗) and r=-0.930(∗∗)) and dough stability (r=0.901(∗∗) and r=-0.979(∗∗)). Peak I was associated with R/E ratio (r=0.745(∗∗)), gluten index (r=0.959(∗∗)), and gliadin/glutenin ratio (r=-0.952(∗∗)), while peak II influenced inversely as expected. Peak I exhibited positive statistical significance with bread loaf volume (r=0.848(∗∗)); however, peak II had negative (r=-0.818(∗∗)) impact. Bread firmness increased with increment in peak II (r=0.625(∗∗)), and decreased with accretion in peak I (r=-0.623(∗∗)).

  16. Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration.

    PubMed

    Fu, Li; Zhang, Fuming; Li, Guoyun; Onishi, Akihiro; Bhaskar, Ujjwal; Sun, Peilong; Linhardt, Robert J

    2014-05-01

    The standard process for preparing the low-molecular-weight heparin (LMWH) tinzaparin, through the partial enzymatic depolymerization of heparin, results in a reduced yield because of the formation of a high content of undesired disaccharides and tetrasaccharides. An enzymatic ultrafiltration reactor for LMWH preparation was developed to overcome this problem. The behavior, of the heparin oligosaccharides and polysaccharides using various membranes and conditions, was investigated to optimize this reactor. A novel product, LMWH-II, was produced from the controlled depolymerization of heparin using heparin lyase II in this optimized ultrafiltration reactor. Enzymatic ultrafiltration provides easy control and high yields (>80%) of LMWH-II. The molecular weight properties of LMWH-II were similar to other commercial LMWHs. The structure of LMWH-II closely matched heparin's core structural features. Most of the common process artifacts, present in many commercial LWMHs, were eliminated as demonstrated by 1D and 2D nuclear magnetic resonance spectroscopy. The antithrombin III and platelet factor-4 binding affinity of LMWH-II were comparable to commercial LMWHs, as was its in vitro anticoagulant activity.

  17. Determination of molecular weight of hyaluronic acid by near-infrared spectroscopy.

    PubMed

    Dong, Qin; Zang, Hengchang; Liu, Aihua; Yang, Guilan; Sun, Chunxiao; Sui, Linyan; Wang, Pei; Li, Lian

    2010-11-02

    This paper attempted the feasibility to determine the molecular weight of hyaluronic acid with near-infrared (NIR) diffuse reflectance spectroscopy. In this work, 46 experimental samples of hyaluronic acid powder were analyzed by partial least square (PLS) regression multivariate calibration method in the selected region of NIR spectra. The leave-one-out cross-validation method was used for the PLS model selection criterion. The accuracy of the final model was evaluated according to correlation coefficient of prediction set (Rp) and root mean square error of prediction set (RMSEP). The repeatability was verified through repeated measurement of spectra coupled with an appropriate chi-square test. Finally, the optimal calibration model was obtained with Rp=0.9814 and RMSEP=88.32 when using Savitzky-Golay first (SG-1st) derivative with 9 smoothing points spectral preprocessing method. The parameters above and repeatability of NIR spectroscopy obtained from chi-square test were both within the range of permissible error in factories. This study demonstrated that NIR spectroscopy was superior to conventional methods for the fast determination of molecular weight of hyaluronic acid.

  18. UV curable lens production using molecular weight controlled PEEK based acrylic oligomer (Ac-PEEK).

    PubMed

    İnan, Tulay Y; Yıldız, Emel; Karaca, Birsen; Dogan, Hacer; Vatansever, Alican; Nalbant, Muhammed; Eken, Koray

    2014-08-01

    We produced UV curable lenses with properties blocking short wave UV light. In the UV-curable formulations, we used an oligomer (Ac-PEEK) with another urethan oligomer (Mw = 2000). Radically active, molecular weight controlled Ac-PEEK was obtained by reacting 2-hydroxyl ethyl methacrylate with molecular- weight- controlled and isocyanate terminated PEEK (Mn = 4500). We characterized all synthesized monomer, oligomer and optical materials with UV/Vis spectrophotometer with interferogram, elemental analyser, mass spectrophotometer, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermal gravimetric analyzer, differential scanning calorimeter, scanning electron microscopy and gas chromatography. Results suggested that newly synthesized oligomer with the structure of PEEK absorbs short wave UV-light. Ageing tests [ISO 11979-5, Ophthalmic implants-intraocular lenses (IOL)-Part 5: Biocompatibility] performed on the IOL materials were successful. High contact angle of the obtained lenses suggests that all lenses were hydrophobic and SEM results revealed that lenses are morphologically homogeneous. Based on all positive properties just mentioned, we safely conclude that the lenses produced in this study are very promising for IOL production.

  19. High-molecular-weight poly(Gly-Val-Gly-Val-Pro) synthesis through microwave irradiation.

    PubMed

    Goto, Mitsuaki; Endo, Takeshi

    2016-07-01

    In this study, we synthesized a polypeptide from its pentapeptide unit using microwave irradiation. Effective methods for polypeptide synthesis from unit peptides have not been reported. Here, we used a key elastin peptide, H-GlyValGlyValPro-OH (GVGVP), as the monomer peptide. It is difficult to obtain poly(Gly-Val-Gly-Val-Pro) (poly(GVGVP)) from the pentapeptide unit of elastin, GVGVP, via polycondensation. Poly(GVGVP) prepared from genetically recombinant Escherichia coli is a well-known temperature-sensitive polypeptide, and this temperature sensitivity is known as the lower critical solution temperature. When microwave irradiation was performed in the presence of various additives, the pentapeptide (GVGVP) polycondensation reaction proceeded smoothly, resulting in a product with a high molecular weight in a relatively good yield. The reaction conditions, like microwave irradiation, coupling agents, and solvents, were optimized to increase the reaction efficiency. The product exhibited a molecular weight greater than Mr 7000. Further, the product could be synthesized on a gram scale. The synthesized polypeptide exhibited a temperature sensitivity that was similar to that of poly(GVGVP) prepared from genetically recombinant E. coli. Therefore, this technique offers a facile and quick approach to prepare polypeptides in large amounts. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.

  20. Molecular-weight-dependent changes in morphology of solution-grown polyethylene single crystals.

    PubMed

    Zhang, Bin; Chen, Jingbo; Baier, Moritz C; Mecking, Stefan