Structures of human cytosolic NADP-dependent isocitrate dehydrogenase reveal a novel self-regulatory mechanism of activity.

PubMed

Xu, Xiang; Zhao, Jingyue; Xu, Zhen; Peng, Baozhen; Huang, Qiuhua; Arnold, Eddy; Ding, Jianping

2004-08-06

Isocitrate dehydrogenases (IDHs) catalyze the oxidative decarboxylation of isocitrate to alpha-ketoglutarate, and regulation of the enzymatic activity of IDHs is crucial for their biological functions. Bacterial IDHs are reversibly regulated by phosphorylation of a strictly conserved serine residue at the active site. Eukaryotic NADP-dependent IDHs (NADP-IDHs) have been shown to have diverse important biological functions; however, their regulatory mechanism remains unclear. Structural studies of human cytosolic NADP-IDH (HcIDH) in complex with NADP and in complex with NADP, isocitrate, and Ca2+ reveal three biologically relevant conformational states of the enzyme that differ substantially in the structure of the active site and in the overall structure. A structural segment at the active site that forms a conserved alpha-helix in all known NADP-IDH structures assumes a loop conformation in the open, inactive form of HcIDH; a partially unraveled alpha-helix in the semi-open, intermediate form; and an alpha-helix in the closed, active form. The side chain of Asp279 of this segment occupies the isocitrate-binding site and forms hydrogen bonds with Ser94 (the equivalent of the phosphorylation site in bacterial IDHs) in the inactive form and chelates the metal ion in the active form. The structural data led us to propose a novel self-regulatory mechanism for HcIDH that mimics the phosphorylation mechanism used by the bacterial homologs, consistent with biochemical and biological data. This mechanism might be applicable to other eukaryotic NADP-IDHs. The results also provide insights into the recognition and specificity of substrate and cofactor by eukaryotic NADP-IDHs.

STRUCTURE-ACTIVITY RELATIONSHIP STUIDES AND THEIR ROLE IN PREDICTING AND INVESTIGATING CHEMICAL TOXICITY

EPA Science Inventory

Structure-Activity Relationship Studies and their Role in Predicting and Investigating Chemical Toxicity

Structure-activity relationships (SAR) represent attempts to generalize chemical information relative to biological activity for the twin purposes of generating insigh...

Investigation of innovative synthesis of biologically active compounds on the basis of newly developed reactions.

PubMed

Honda, Toshio

2012-01-01

Synthesis of biologically active compounds, including natural products and pharmaceutical agents, is an important and interesting research area since the large structural diversity and complexity of bioactive compounds make them an important source of leads and scaffolds in drug discovery and development. Many structurally and also biologically interesting compounds, including marine natural products, have been isolated from nature and have also been prepared on the basis of a computational design for the purpose of developing medicinal chemistry. In order to obtain a wide variety of derivatives of biologically active compounds from the viewpoint of medicinal chemistry, it is essential to establish efficient synthetic procedures for desired targets. Newly developed reactions should also be used for efficient synthesis of desired compounds. Thus, recent progress in the synthesis of biologically active compounds by focusing on the development of new reactions is summarized in this review article.

THE PRACTICE OF STRUCTURE ACTIVITY RELATIONSHIPS (SAR) IN TOXICOLOGY

EPA Science Inventory

Both qualitative and quantitative modeling methods relating chemical structure to biological activity, called structure-activity relationship analyses or SAR, are applied to the prediction and characterization of chemical toxicity. This minireview will discuss some generic issue...

CONSIDERATION OF REACTION INTERMEDIATES IN STRUCTURE-ACTIVITY RELATIONSHIPS: A KEY TO UNDERSTANDING AND PREDICTION

EPA Science Inventory

Consideration of Reaction Intermediates in Structure- Activity Relationships: A Key to Understanding and Prediction

A structure-activity relationship (SAR) represents an empirical means for generalizing chemical information relative to biological activity, and is frequent...

Sea Cucumber Glycosides: Chemical Structures, Producing Species and Important Biological Properties

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Rahman, M. Aminur; Islam, Mohamad Tofazzal

2017-01-01

Sea cucumbers belonging to echinoderm are traditionally used as tonic food in China and other Asian countries. They produce abundant biologically active triterpene glycosides. More than 300 triterpene glycosides have been isolated and characterized from various species of sea cucumbers, which are classified as holostane and nonholostane depending on the presence or absence of a specific structural unit γ(18,20)-lactone in the aglycone. Triterpene glycosides contain a carbohydrate chain up to six monosaccharide units mainly consisting of d-xylose, 3-O-methy-d-xylose, d-glucose, 3-O-methyl-d-glucose, and d-quinovose. Cytotoxicity is the common biological property of triterpene glycosides isolated from sea cucumbers. Besides cytotoxicity, triterpene glycosides also exhibit antifungal, antiviral and hemolytic activities. This review updates and summarizes our understanding on diverse chemical structures of triterpene glycosides from various species of sea cucumbers and their important biological activities. Mechanisms of action and structural–activity relationships (SARs) of sea cucumber glycosides are also discussed briefly. PMID:29039760

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

PubMed Central

Vardanyan, Ruben S; Hruby, Victor J

2014-01-01

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure–biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed. PMID:24635521

Clerodane diterpenes: sources, structures, and biological activities†

PubMed Central

Li, Rongtao; Morris-Natschke, Susan L.; Lee, Kuo-Hsiung

2016-01-01

The clerodane diterpenoids are a widespread class of secondary metabolites and have been found in several hundreds of plant species from various families and in organisms from other taxonomic groups. These substances have attracted interest in recent years due to their notable biological activities, particularly insect antifeedant properties. In addition, the major active clerodanes of Salvia divinorum can be used as novel opioid receptor probes, allowing greater insight into opioid receptor-mediated phenomena, as well as opening additional areas for chemical investigation. This article provides extensive coverage of naturally occurring clerodane diterpenes discovered from 1990 until 2015, and follows up on the 1992 review by Merritt and Ley in this same journal. The distribution, chemotaxonomic significance, chemical structures, and biological activities of clerodane diterpenes are summarized. In the cases where sufficient information is available, structure activity relationship (SAR) correlations and mode of action of active clerodanes have been presented. PMID:27433555

The Relative Importance of Spatial Versus Temporal Structure in the Perception of Biological Motion: An Event-Related Potential Study

ERIC Educational Resources Information Center

Hirai, Masahiro; Hiraki, Kazuo

2006-01-01

We investigated how the spatiotemporal structure of animations of biological motion (BM) affects brain activity. We measured event-related potentials (ERPs) during the perception of BM under four conditions: normal spatial and temporal structure; scrambled spatial and normal temporal structure; normal spatial and scrambled temporal structure; and…

Cyclobutane-Containing Alkaloids: Origin, Synthesis, and Biological Activities

PubMed Central

Sergeiko, Anastasia; Poroikov, Vladimir V; Hanuš, Lumir O; Dembitsky, Valery M

2008-01-01

Present review describes research on novel natural cyclobutane-containing alkaloids isolated from terrestrial and marine species. More than 60 biological active compounds have been confirmed to have antimicrobial, antibacterial, antitumor, and other activities. The structures, synthesis, origins, and biological activities of a selection of cyclobutane-containing alkaloids are reviewed. With the computer program PASS some additional biological activities are also predicted, which point toward new possible applications of these compounds. This review emphasizes the role of cyclobutane-containing alkaloids as an important source of leads for drug discovery. PMID:19696873

Photoelectron spectra and biological activity of cinnamic acid derivatives revisited.

PubMed

Novak, Igor; Klasinc, Leo; McGlynn, Sean P

2018-01-15

The electronic structures of several derivatives of cinnamic acid have been studied by UV photoelectron spectroscopy (UPS) and Green's function quantum chemical calculations. The spectra reveal the presence of dimers in the gas phase for p-coumaric and ferulic acids. The electronic structure analysis has been related to the biological properties of these compounds through the analysis of some structure-activity relationships (SAR). Copyright © 2017 Elsevier B.V. All rights reserved.

TOPICAL REVIEW: Protein stability and enzyme activity at extreme biological temperatures

NASA Astrophysics Data System (ADS)

Feller, Georges

2010-08-01

Psychrophilic microorganisms thrive in permanently cold environments, even at subzero temperatures. To maintain metabolic rates compatible with sustained life, they have improved the dynamics of their protein structures, thereby enabling appropriate molecular motions required for biological activity at low temperatures. As a consequence of this structural flexibility, psychrophilic proteins are unstable and heat-labile. In the upper range of biological temperatures, thermophiles and hyperthermophiles grow at temperatures > 100 °C and synthesize ultra-stable proteins. However, thermophilic enzymes are nearly inactive at room temperature as a result of their compactness and rigidity. At the molecular level, both types of extremophilic proteins have adapted the same structural factors, but in opposite directions, to address either activity at low temperatures or stability in hot environments. A model based on folding funnels is proposed accounting for the stability-activity relationships in extremophilic proteins.

Investigating biological activity spectrum for novel quinoline analogues.

PubMed

Musiol, Robert; Jampilek, Josef; Kralova, Katarina; Richardson, Des R; Kalinowski, Danuta; Podeszwa, Barbara; Finster, Jacek; Niedbala, Halina; Palka, Anna; Polanski, Jaroslaw

2007-02-01

The lack of the wide spectrum of biological data is an important obstacle preventing the efficient molecular design. Quinoline derivatives are known to exhibit a variety of biological effects. In the current publication, we tested a series of novel quinoline analogues for their photosynthesis-inhibiting activity (the inhibition of photosynthetic electron transport in spinach chloroplasts (Spinacia oleracea L.) and the reduction of chlorophyll content in Chlorella vulgaris Beij.). Moreover, antiproliferative activity was measured using SK-N-MC neuroepithelioma cell line. We described the structure-activity relationships (SAR) between the chemical structure and biological effects of the synthesized compounds. We also measured the lipophilicity of the novel compounds by means of the RP-HPLC and illustrate the relationships between the RP-HPLC retention parameter logK (the logarithm of capacity factor K) and logP data calculated by available programs.

Assessment of pollution impact on biological activity and structure of seabed bacterial communities in the Port of Livorno (Italy).

PubMed

Iannelli, Renato; Bianchi, Veronica; Macci, Cristina; Peruzzi, Eleonora; Chiellini, Carolina; Petroni, Giulio; Masciandaro, Grazia

2012-06-01

The main objective of this study was to assess the impact of pollution on seabed bacterial diversity, structure and activity in the Port of Livorno. Samples of seabed sediments taken from five selected sites within the port were subjected to chemical analyses, enzymatic activity detection, bacterial count and biomolecular analysis. Five different statistics were used to correlate the level of contamination with the detected biological indicators. The results showed that the port is mainly contaminated by variable levels of petroleum hydrocarbons and heavy metals, which affect the structure and activity of the bacterial population. Irrespective of pollution levels, the bacterial diversity did not diverge significantly among the assessed sites and samples, and no dominance was observed. The type of impact of hydrocarbons and heavy metals was controversial, thus enforcing the supposition that the structure of the bacterial community is mainly driven by the levels of nutrients. The combined use of chemical and biological essays resulted in an in-depth observation and analysis of the existing links between pollution macro-indicators and biological response of seabed bacterial communities. Copyright © 2012 Elsevier B.V. All rights reserved.

In Vitro Phytotoxicity and Antioxidant Activity of Selected Flavonoids

PubMed Central

De Martino, Laura; Mencherini, Teresa; Mancini, Emilia; Aquino, Rita Patrizia; De Almeida, Luiz Fernando Rolim; De Feo, Vincenzo

2012-01-01

The knowledge of flavonoids involved in plant-plant interactions and their mechanisms of action are poor and, moreover, the structural characteristics required for these biological activities are scarcely known. The objective of this work was to study the possible in vitro phytotoxic effects of 27 flavonoids on the germination and early radical growth of Raphanus sativus L. and Lepidium sativum L., with the aim to evaluate the possible structure/activity relationship. Moreover, the antioxidant activity of the same compounds was also evaluated. Generally, in response to various tested flavonoids, germination was only slightly affected, whereas significant differences were observed in the activity of the various tested flavonoids against radical elongation. DPPH test confirms the antioxidant activity of luteolin, quercetin, catechol, morin, and catechin. The biological activity recorded is discussed in relation to the structure of compounds and their capability to interact with cell structures and physiology. No correlation was found between phytotoxic and antioxidant activities. PMID:22754304

Advances on Semisynthesis, Total Synthesis, and Structure-Activity Relationships of Honokiol and Magnolol Derivatives.

PubMed

Yang, Chun; Zhi, Xiaoyan; Xu, Hui

2016-01-01

Honokiol and magnolol (an isomer of honokiol) are small-molecule polyphenols isolated from the barks of Magnolia officinalis, which have been widely used in traditional Chinese and Japanese medicines. In the last decade, a variety of biological properties of honokiol and magnolol (e.g., anti-oxidativity, antitumor activity, anti-depressant activity, anti-inflammatory activity, neuroprotective activity, anti-diabetic activity, antiviral activity, and antimicrobial activity) have been reported. Meanwhile, certain mechanisms of action of some biological activities were also investigated. Moreover, many analogs of honokiol and magnolol were prepared by structural modification or total synthesis, and some exhibited very potent pharmacological activities with improved water solubility. Therefore, the present review will provide a systematic coverage on recent developments of honokiol and magnolol derivatives in regard to semisynthesis, total synthesis, and structure-activity relationships from 2000 up to now.

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins.

PubMed

Uversky, Vladimir N

2016-03-25

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives.

PubMed

Šegan, Sandra; Trifković, Jelena; Verbić, Tatjana; Opsenica, Dejan; Zlatović, Mario; Burnett, James; Šolaja, Bogdan; Milojković-Opsenica, Dušanka

2013-01-01

The physicochemical properties, retention parameters (R(M)(0)), partition coefficients (logP(OW)), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R(M)(0), logP(OW), and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. Copyright © 2012 Elsevier B.V. All rights reserved.

Structural Biology Guides Antibiotic Discovery

ERIC Educational Resources Information Center

Polyak, Steven

2014-01-01

Modern drug discovery programs require the contribution of researchers in a number of specialist areas. One of these areas is structural biology. Using X-ray crystallography, the molecular basis of how a drug binds to its biological target and exerts its mode of action can be defined. For example, a drug that binds into the active site of an…

Relevance of rhodopsin studies for GPCR activation.

PubMed

Deupi, Xavier

2014-05-01

Rhodopsin, the dim-light photoreceptor present in the rod cells of the retina, is both a retinal-binding protein and a G protein-coupled receptor (GPCR). Due to this conjunction, it benefits from an arsenal of spectroscopy techniques that can be used for its characterization, while being a model system for the important family of Class A (also referred to as "rhodopsin-like") GPCRs. For instance, rhodopsin has been a crucial player in the field of GPCR structural biology. Until 2007, it was the only GPCR for which a high-resolution crystal structure was available, so all structure-activity analyses on GPCRs, from structure-based drug discovery to studies of structural changes upon activation, were based on rhodopsin. At present, about a third of currently available GPCR structures are still from rhodopsin. In this review, I show some examples of how these structures can still be used to gain insight into general aspects of GPCR activation. First, the analysis of the third intracellular loop in rhodopsin structures allows us to gain an understanding of the structural and dynamic properties of this region, which is absent (due to protein engineering or poor electron density) in most of the currently available GPCR structures. Second, a detailed analysis of the structure of the transmembrane domains in inactive, intermediate and active rhodopsin structures allows us to detect early conformational changes in the process of ligand-induced GPCR activation. Finally, the analysis of a conserved ligand-activated transmission switch in the transmembrane bundle of GPCRs in the context of the rhodopsin activation cycle, allows us to suggest that the structures of many of the currently available agonist-bound GPCRs may correspond to intermediate active states. While the focus in GPCR structural biology is inevitably moving away from rhodopsin, in other aspects rhodopsin is still at the forefront. For instance, the first studies of the structural basis of disease mutants in GPCRs, or the most detailed analysis of cellular GPCR signal transduction networks using a systems biology approach, have been carried out in rhodopsin. Finally, due again to its unique properties among GPCRs, rhodopsin will likely play an important role in the application of X-ray free electron laser crystallography to time-resolved structural biology in membrane proteins. Rhodopsin, thus, still remains relevant as a model system to study the molecular mechanisms of GPCR activation. This article is part of a Special Issue entitled: Retinal Proteins-You can teach an old dog new tricks. © 2013 Elsevier B.V. All rights reserved.

New Synthetic Methods for Hypericum Natural Products

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeon, Insik

Organic chemistry has served as a solid foundation for interdisciplinary research areas, such as molecular biology and medicinal chemistry. An understanding of the biological activities and structural elucidations of natural products can lead to the development of clinically valuable therapeutic options. The advancements of modern synthetic methodologies allow for more elaborate and concise natural product syntheses. The theme of this study centers on the synthesis of natural products with particularly challenging structures and interesting biological activities. The synthetic expertise developed here will be applicable to analog syntheses and to other research problems.

Synthesis and Biological Evaluation of Ginsenoside Compound K Derivatives as a Novel Class of LXRα Activator.

PubMed

Huang, Yan; Liu, Hongmei; Zhang, Yingxian; Li, Jin; Wang, Chenping; Zhou, Li; Jia, Yi; Li, Xiaohui

2017-07-24

Compound K is one of the active metabolites of Panaxnotoginseng saponins, which could attenuate the formation of atherosclerosis in mice modelsvia activating LXRα. We synthesized and evaluated a series of ginsenoside compound K derivatives modified with short chain fatty acids. All of the structures of this class of ginsenoside compound K derivative exhibited comparable or better biological activity than ginsenoside compound K. Especially structure 1 exhibited the best potency (cholesteryl ester content: 41.51%; expression of ABCA1 mRNA: 319%) and low cytotoxicity.

Structure-Based Virtual Screening of Protein Tyrosine Phosphatase Inhibitors: Significance, Challenges, and Solutions.

PubMed

Reddy, Rallabandi Harikrishna; Kim, Hackyoung; Cha, Seungbin; Lee, Bongsoo; Kim, Young Jun

2017-05-28

Phosphorylation, a critical mechanism in biological systems, is estimated to be indispensable for about 30% of key biological activities, such as cell cycle progression, migration, and division. It is synergistically balanced by kinases and phosphatases, and any deviation from this balance leads to disease conditions. Pathway or biological activity-based abnormalities in phosphorylation and the type of involved phosphatase influence the outcome, and cause diverse diseases ranging from diabetes, rheumatoid arthritis, and numerous cancers. Protein tyrosine phosphatases (PTPs) are of prime importance in the process of dephosphorylation and catalyze several biological functions. Abnormal PTP activities are reported to result in several human diseases. Consequently, there is an increased demand for potential PTP inhibitory small molecules. Several strategies in structure-based drug designing techniques for potential inhibitory small molecules of PTPs have been explored along with traditional drug designing methods in order to overcome the hurdles in PTP inhibitor discovery. In this review, we discuss druggable PTPs and structure-based virtual screening efforts for successful PTP inhibitor design.

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

PubMed Central

2017-01-01

γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials. PMID:28640622

The activation of fibroblast growth factors by heparin: synthesis, structure, and biological activity of heparin-like oligosaccharides.

PubMed

de Paz, J L; Angulo, J; Lassaletta, J M; Nieto, P M; Redondo-Horcajo, M; Lozano, R M; Giménez-Gallego, G; Martín-Lomas, M

2001-09-03

An effective strategy has been designed for the synthesis of oligosaccharides of different sizes structurally related to the regular region of heparin; this is illustrated by the preparation of hexasaccharide 1 and octasaccharide 2. This synthetic strategy provides the oligosaccharide sequence containing a D-glucosamine unit at the nonreducing end that is not available either by enzymatic or chemical degradation of heparin. It may permit, after slight modifications, the preparation of oligosaccharide fragments with different charge distribution as well. NMR spectroscopy and molecular dynamics simulations have shown that the overall structure of 1 in solution is a stable right-hand helix with four residues per turn. Hexasaccharide 1 and, most likely, octasaccharide 2 are, therefore, chemically well-defined structural models of naturally occurring heparin-like oligosaccharides for use in binding and biological activity studies. Both compounds 1 and 2 induce the mitogenic activity of acid fibroblast growth factor (FGF1), with the half-maximum activating concentration of 2 being equivalent to that of heparin. Sedimentation equilibrium analysis with compound 2 suggests that heparin-induced FGF1 dimerization is not an absolute requirement for biological activity.

Synthesis, spectroscopic, crystal structure, biological activities and theoretical studies of 2-[(2E)-2-(2-chloro-6-fluorobenzylidene)hydrazinyl]pyridine

NASA Astrophysics Data System (ADS)

Dilek Özçelik, Nefise; Tunç, Tuncay; Çatak Çelik, Raziye; Erzengin, Mahmut; Özışık, Hacı

2017-05-01

We report in this paper the synthesis, spectroscopic, crystal structure, biological activities and theoretical results of the title compound. The crystal structure was defined by the X-ray diffraction (XRD) method. In addition, this newly synthesized hydrazone derivative was also subjected to its possible antioxidant activity with free radical scavenging ability of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals using butylated hydroxytoluene (BHT) as standard antioxidant. The structural calculations were performed by the density functional theory using the B3LYP method with 6-311++G(2d,2p) basis set. The calculated values were compared with experimental results.

Lipo-chitin oligosaccharides, plant symbiosis signalling molecules that modulate mammalian angiogenesis in vitro.

PubMed

Djordjevic, Michael A; Bezos, Anna; Susanti; Marmuse, Laurence; Driguez, Hugues; Samain, Eric; Vauzeilles, Boris; Beau, Jean-Marie; Kordbacheh, Farzaneh; Rolfe, Barry G; Schwörer, Ralf; Daines, Alison M; Gresshoff, Peter M; Parish, Christopher R

2014-01-01

Lipochitin oligosaccharides (LCOs) are signaling molecules required by ecologically and agronomically important bacteria and fungi to establish symbioses with diverse land plants. In plants, oligo-chitins and LCOs can differentially interact with different lysin motif (LysM) receptors and affect innate immunity responses or symbiosis-related pathways. In animals, oligo-chitins also induce innate immunity and other physiological responses but LCO recognition has not been demonstrated. Here LCO and LCO-like compounds are shown to be biologically active in mammals in a structure dependent way through the modulation of angiogenesis, a tightly-regulated process involving the induction and growth of new blood vessels from existing vessels. The testing of 24 LCO, LCO-like or oligo-chitin compounds resulted in structure-dependent effects on angiogenesis in vitro leading to promotion, or inhibition or nil effects. Like plants, the mammalian LCO biological activity depended upon the presence and type of terminal substitutions. Un-substituted oligo-chitins of similar chain lengths were unable to modulate angiogenesis indicating that mammalian cells, like plant cells, can distinguish between LCOs and un-substituted oligo-chitins. The cellular mode-of-action of the biologically active LCOs in mammals was determined. The stimulation or inhibition of endothelial cell adhesion to vitronectin or fibronectin correlated with their pro- or anti-angiogenic activity. Importantly, novel and more easily synthesised LCO-like disaccharide molecules were also biologically active and de-acetylated chitobiose was shown to be the primary structural basis of recognition. Given this, simpler chitin disaccharides derivatives based on the structure of biologically active LCOs were synthesised and purified and these showed biological activity in mammalian cells. Since important chronic disease states are linked to either insufficient or excessive angiogenesis, LCO and LCO-like molecules may have the potential to be a new, carbohydrate-based class of therapeutics for modulating angiogenesis.

Design, synthesis and biological evaluation of paclitaxel-mimics possessing only the oxetane D-ring and side chain structures.

PubMed

Chen, Xing-Xiu; Gao, Feng; Wang, Qi; Huang, Xing; Wang, Dan

2014-01-01

Two spiro paclitaxel-mimics consisting only of an oxetane D-ring and a C-13 side chain were designed and synthesized on the basis of analysis of structure-activity relationships (SAR) of paclitaxel. In vitro microtubule-stabilizing and antiproliferative assays indicated a moderate weaker activity of the mimics than paclitaxel, but which still represented the first example of simplified paclitaxel analogues with significant anti-tumor biological activity. Copyright © 2013 Elsevier B.V. All rights reserved.

Synthesis, structural studies and biological properties of new TBA analogues containing an acyclic nucleotide.

PubMed

Coppola, Teresa; Varra, Michela; Oliviero, Giorgia; Galeone, Aldo; D'Isa, Giuliana; Mayol, Luciano; Morelli, Elena; Bucci, Maria-Rosaria; Vellecco, Valentina; Cirino, Giuseppe; Borbone, Nicola

2008-09-01

A new modified acyclic nucleoside, namely N(1)-(3-hydroxy-2-hydroxymethyl-2-methylpropyl)-thymidine, was synthesized and transformed into a building block useful for oligonucleotide (ON) automated synthesis. A series of modified thrombin binding aptamers (TBAs) in which the new acyclic nucleoside replaces, one at the time, the thymidine residues were then synthesized and characterized by UV, CD, MS, and (1)H NMR. The biological activity of the resulting TBAs was tested by Prothrombin Time assay (PT assay) and by purified fibrinogen clotting assay. From a structural point of view, nearly all the new TBA analogues show a similar behavior as the unmodified counterpart, being able to fold into a bimolecular or monomolecular quadruplex structure depending on the nature of monovalent cations (sodium or potassium) coordinated in the quadruplex core. From the comparison of structural and biological data, some important structure-activity relationships emerged, particularly when the modification involved the TT loops. In agreement with previous studies we found that the folding ability of TBA analogues is more affected by modifications involving positions 4 and 13, rather than positions 3 and 12. On the other hand, the highest anti-thrombin activities were detected for aptamers containing the modification at T13 or T12 positions, thus indicating that the effects produced by the introduction of the acyclic nucleoside on the biological activity are not tightly connected with structure stabilities. It is noteworthy that the modification at T7 produces an ON being more stable and active than the natural TBA.

Effect of Locked-Nucleic Acid on a Biologically Active G-Quadruplex. A Structure-Activity Relationship of the Thrombin Aptamer

PubMed Central

Bonifacio, Laura; Church, Frank C.; Jarstfer, Michael B.

2008-01-01

Here we tested the ability to augment the biological activity of the thrombin aptamer, d(GGTTGGTGTGGTTGG), by using locked nucleic acid (LNA) to influence its G-quadruplex structure. Compared to un-substituted control aptamer, LNA-containing aptamers displayed varying degrees of thrombin inhibition. Aptamers with LNA substituted in either positions G5, T7, or G8 showed decreased thrombin inhibition, whereas LNA at position G2 displayed activity comparable to un-substituted control aptamer. Interestingly, the thermal stability of the substituted aptamers does not correlate to activity – the more stable aptamers with LNA in position G5, T7, or G8 showed the least thrombin inhibition, while a less stable aptamer with LNA at G2 was as active as the un-substituted aptamer. These results suggest that LNA substitution at sites G5, T7, and G8 directly perturbs aptamer-thrombin affinity. This further implies that for the thrombin aptamer, activity is not dictated solely by the stability of the G-quadruplex structure, but by specific interactions between the central TGT loop and thrombin and that LNA can be tolerated in a biologically active nucleic acid structure albeit in a position dependent fashion. PMID:19325759

[Characteristics of microbial community and operation efficiency in biofilter process for drinking water purification].

PubMed

Xiang, Hong; Lü, Xi-Wu; Yang, Fei; Yin, Li-Hong; Zhu, Guang-Can

2011-04-01

In order to explore characteristics of microbial community and operation efficiency in biofilter (biologically-enhanced active filter and biological activated carbon filter) process for drinking water purification, Biolog and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) techniques were applied to analyze the metabolic function and structure of microbial community developing in biofilters. Water quality parameters, such as NH; -N, NO; -N, permanganate index, UV254 and BDOC etc, were determined in inflow and outflow of biofilters for investigation of operation efficiency of the biofilters. The results show that metabolic capacity of microbial community of the raw water is reduced after the biofilters, which reflect that metabolically active microbial communities in the raw water can be intercepted by biofilters. After 6 months operation of biofilters, the metabolic profiles of microbial communities are similar between two kinds of biologically-enhanced active filters, and utilization of carbon sources of microbial communities in the two filters are 73.4% and 75.5%, respectively. The metabolic profiles of microbial communities in two biological activated carbon filters showed significant difference. The carbon source utilization rate of microbial community in granule-activated carbon filter is 79.6%, which is obviously higher than 53.8% of the rate in the columnar activated carbon filter (p < 0.01). The analysis results of PCR-SSCP indicate that microbial communities in each biofilter are variety, but the structure of dominant microorganisms is similar among different biofilters. The results also show that the packing materials had little effect on the structure and metabolic function of microbial community in biologically-enhanced active filters, and the difference between two biofilters for the water purification efficiency was not significant (p > 0.05). However, in biological activated carbon filters, granule-activated carbon is conducive to microbial growth and reproduction, and the microbial communities in the biofilter present high metabolic activities, and the removal efficiency for NH4(+)-N, permanganate index and BDOC is better than the columnar activated carbon filter(p < 0.05). The results also suggest that operation efficiency of biofilter is related to the metabolic capacity of microbial community in biofilter.

Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins*

PubMed Central

2016-01-01

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. PMID:26851286

Thin film composition with biological substance and method of making

DOEpatents

Campbell, Allison A.; Song, Lin

1999-01-01

The invention provides a thin-film composition comprising an underlying substrate of a first material including a plurality of attachment sites; a plurality of functional groups chemically attached to the attachment sites of the underlying substrate; and a thin film of a second material deposited onto the attachment sites of the underlying substrate, and a biologically active substance deposited with the thin-film. Preferably the functional groups are attached to a self assembling monolayer attached to the underlying substrate. Preferred functional groups attached to the underlying substrate are chosen from the group consisting of carboxylates, sulfonates, phosphates, optionally substituted, linear or cyclo, alkyl, alkene, alkyne, aryl, alkylaryl, amine, hydroxyl, thiol, silyl, phosphoryl, cyano, metallocenyl, carbonyl, and polyphosphate. Preferred materials for the underlying substrate are selected from the group consisting of a metal, a metal alloy, a plastic, a polymer, a proteic film, a membrane, a glass or a ceramic. The second material is selected from the group consisting of inorganic crystalline structures, inorganic amorphus structures, organic crystalline structures, and organic amorphus structures. Preferred second materials are phosphates, especially calcium phosphates and most particularly calcium apatite. The biologically active molecule is a protein, peptide, DNA segment, RNA segment, nucleotide, polynucleotide, nucleoside, antibiotic, antimicrobal, radioisotope, chelated radioisotope, chelated metal, metal salt, anti-inflamatory, steriod, nonsteriod anti-inflammatory, analgesic, antihistamine, receptor binding agent, or chemotherapeutic agent, or other biologically active material. Preferably the biologically active molecule is an osteogenic factor the compositions listed above.

Synthesis and biological evaluation of manzamine analogues.

PubMed

Winkler, Jeffrey D; Londregan, Allyn T; Ragains, Justin R; Hamann, Mark T

2006-07-20

[Structure: see text] The synthesis and biological evaluation of a series of analogues of manzamine A, representing partial structures of the pentacyclic ABCDE diamine core, is described. All new compounds were screened against Plasmodium falciparum and demonstrated attenuated antimalarial activity relative to that of manzamine A.

DFT study of quercetin activated forms involved in antiradical, antioxidant, and prooxidant biological processes.

PubMed

Fiorucci, Sébastien; Golebiowski, Jérôme; Cabrol-Bass, Daniel; Antonczak, Serge

2007-02-07

Quercetin, one of the most representative flavonoid compounds, is involved in antiradical, antioxidant, and prooxidant biological processes. Despite a constant increase of knowledge on both positive and negative activities of quercetin, it is unclear which activated form (quinone, semiquinone, or deprotonated) actually plays a role in each of these processes. Structural, electronic, and energetic characteristics of quercetin, as well as the influence of a copper ion on all of these parameters, are studied by means of quantum chemical electronic structure calculations. Introduction of thermodynamic cycles together with the role of coreactive compounds, such as reactive oxygen species, gives a glimpse of the most probable reaction schemes. Such a theoretical approach provides another hint to clarify which reaction is likely to occur within the broad range of quercetin biological activities.

Chemical Structure-Biological Activity Models for Pharmacophores’ 3D-Interactions

PubMed Central

Putz, Mihai V.; Duda-Seiman, Corina; Duda-Seiman, Daniel; Putz, Ana-Maria; Alexandrescu, Iulia; Mernea, Maria; Avram, Speranta

2016-01-01

Within medicinal chemistry nowadays, the so-called pharmaco-dynamics seeks for qualitative (for understanding) and quantitative (for predicting) mechanisms/models by which given chemical structure or series of congeners actively act on biological sites either by focused interaction/therapy or by diffuse/hazardous influence. To this aim, the present review exposes three of the fertile directions in approaching the biological activity by chemical structural causes: the special computing trace of the algebraic structure-activity relationship (SPECTRAL-SAR) offering the full analytical counterpart for multi-variate computational regression, the minimal topological difference (MTD) as the revived precursor for comparative molecular field analyses (CoMFA) and comparative molecular similarity indices analysis (CoMSIA); all of these methods and algorithms were presented, discussed and exemplified on relevant chemical medicinal systems as proton pump inhibitors belonging to the 4-indolyl,2-guanidinothiazole class of derivatives blocking the acid secretion from parietal cells in the stomach, the 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine congeners’ (HEPT ligands) antiviral activity against Human Immunodeficiency Virus of first type (HIV-1) and new pharmacophores in treating severe genetic disorders (like depression and psychosis), respectively, all involving 3D pharmacophore interactions. PMID:27399692

Application of biospeckles for assessment of structural and cellular changes in muscle tissue

NASA Astrophysics Data System (ADS)

Maksymenko, Oleksandr P.; Muravsky, Leonid I.; Berezyuk, Mykola I.

2015-09-01

A modified spatial-temporal speckle correlation technique for operational assessment of structural changes in muscle tissues after slaughtering is considered. Coefficient of biological activity as a quantitative indicator of structural changes of biochemical processes in biological tissues is proposed. The experimental results have shown that this coefficient properly evaluates the biological activity of pig and chicken muscle tissue samples. Studying the degradation processes in muscle tissue during long-time storage in a refrigerator by measuring the spatial-temporal dynamics of biospeckle patterns is carried out. The reduction of the bioactivity level of refrigerated muscle tissue samples connected with the initiation of muscle fiber cracks and ruptures, reduction of sarcomeres, nuclei deformation, nuclear chromatin diminishing, and destruction of mitochondria is analyzed.

Humic substances biological activity at the plant-soil interface

PubMed Central

Trevisan, Sara; Francioso, Ornella; Nardi, Serenella

2010-01-01

Humic substances (HS) represent the organic material mainly widespread in nature. HS have positive effects on plant physiology by improving soil structure and fertility and by influencing nutrient uptake and root architecture. The biochemical and molecular mechanisms underlying these events are only partially known. HS have been shown to contain auxin and an “auxin-like” activity of humic substances has been proposed, but support to this hypothesis is fragmentary. In this review article, we are giving an overview of available data concerning molecular structures and biological activities of humic substances, with special emphasis on their hormone-like activities. PMID:20495384

Ferromagnetic nanoparticles containing biologically active alkanolamines: preparation and properties

NASA Astrophysics Data System (ADS)

Segal, I.; Zablotskaya, A.; Lukevics, E.; Maiorov, M.; Zablotsky, D.

2005-12-01

The objective of the present study is to investigate the possibility of sorption on ultrafine magnetic particles of some model biologically active organosilicon alkanolamines, structural analogs of natural biologically active substances, choline and colamine, with increased lipophilicity. Double-coated ferromagnetic samples containing oleic acid, as a first layer, and organosilicon alcanolamines, as a second layer, were obtained and characterized by their physical/chemical (sorption and magnetisation) and biological (toxicity and cytotoxicity) properties. The present results clearly reveal the sorption of the biologically active alkanolamines on the surface of magnetic particles and a principal possibility to coat magnetite directly with biologically active alkanolamines, creating a mono-layer cover. The data presented in the study of cytotoxic properties of the newly obtained ferromagnetic nanoparticles show that it is reasonable to investigate such systems as potential cytotoxic agents. Tables 3, Figs 3, Refs 16.

CURRENT PRACTICES IN QSAR DEVELOPMENT AND APPLICATIONS

EPA Science Inventory

Current Practices in QSAR Development and Applications

Although it is commonly assumed that the structure and properties of a single chemical determines its activity in a particular biological system, it is only through study of how biological activity varies with changes...

Structural Elucidation and Biological Activity of a Highly Regular Fucosylated Glycosaminoglycan from the Edible Sea Cucumber Stichopus herrmanni.

PubMed

Li, Xiaomei; Luo, Lan; Cai, Ying; Yang, Wenjiao; Lin, Lisha; Li, Zi; Gao, Na; Purcell, Steven W; Wu, Mingyi; Zhao, Jinhua

2017-10-25

Edible sea cucumbers are widely used as a health food and medicine. A fucosylated glycosaminoglycan (FG) was purified from the high-value sea cucumber Stichopus herrmanni. Its physicochemical properties and structure were analyzed and characterized by chemical and instrumental methods. Chemical analysis indicated that this FG with a molecular weight of ∼64 kDa is composed of N-acetyl-d-galactosamine, d-glucuronic acid (GlcA), and l-fucose. Structural analysis clarified that the FG contains the chondroitin sulfate E-like backbone, with mostly 2,4-di-O-sulfated (85%) and some 3,4-di-O-sulfated (10%) and 4-O-sulfated (5%) fucose side chains that link to the C3 position of GlcA. This FG is structurally highly regular and homogeneous, differing from the FGs of other sea cucumbers, for its sulfation patterns are simpler. Biological activity assays indicated that it is a strong anticoagulant, inhibiting thrombin and intrinsic factor Xase. Our results expand the knowledge on structural types of FG and illustrate its biological activity as a functional food material.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

PubMed

Olender, Dorota; Żwawiak, Justyna; Zaprutko, Lucjusz

2018-05-29

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Effects of Humic Acids Isolated from Peat of Various Origin on in Vitro Production of Nitric Oxide: a Screening Study.

PubMed

Trofimova, E S; Zykova, M V; Ligacheva, A A; Sherstoboev, E Yu; Zhdanov, V V; Belousov, M V; Yusubov, M S; Krivoshchekov, S V; Danilets, M G; Dygai, A M

2016-09-01

A screening study of biological activity of native humic acids isolated from peat was performed; several physical and chemical parameters of their structures were studied by UV- and infrared spectroscopy. Spectroscopy yielded similar shape of light absorption curves of humic acids of different origin, which can reflect similarity of general structural principles of these substances. Alkaline humic acids have more developed system of polyconjugation, while molecular structures of pyrophosphate humic acids were characterized by higher aromaticity and condensation indexes. Biological activity of the studied humic acids was assessed by NO-stimulating capacity during their culturing with murine peritoneal macrophages in a wide concentration range. It was shown that due to dose-dependent enhancement of NO production humic acids can change the functional state of macrophages towards development of pro-inflammatory properties. These changes were associated with high activity of humic acids isolated by pyrophosphate extraction, which allows considering effects of isolation method on biological activity.

Anticancer effect and structure-activity analysis of marine products isolated from metabolites of mangrove fungi in the South China Sea.

PubMed

Tao, Li-yang; Zhang, Jian-ye; Liang, Yong-ju; Chen, Li-ming; Zhen, Li-sheng; Wang, Fang; Mi, Yan-jun; She, Zhi-gang; To, Kenneth Kin Wah; Lin, Yong-cheng; Fu, Li-wu

2010-04-01

Marine-derived fungi provide plenty of structurally unique and biologically active secondary metabolites. We screened 87 marine products from mangrove fungi in the South China Sea for anticancer activity by MTT assay. 14% of the compounds (11/86) exhibited a potent activity against cancer in vitro. Importantly, some compounds such as compounds 78 and 81 appeared to be promising for treating cancer patients with multidrug resistance, which should encourage more efforts to isolate promising candidates for further development as clinically useful chemotherapeutic drugs. Furthermore, DNA intercalation was not involved in their anticancer activities, as determined by DNA binding assay. On the other hand, the structure-activity analysis indicated that the hydroxyl group was important for their cytotoxic activity and that bulky functional groups such as phenyl rings could result in a loss of biological activity, which will direct the further development of marine product-based derivatives.

Plasma-Induced Degradation of Quercetin Associated with the Enhancement of Biological Activities.

PubMed

Kim, Tae Hoon; Lee, Jaemin; Kim, Hyun-Joo; Jo, Cheorun

2017-08-16

Nonthermal plasma is a promising technology to improve the safety and to extend the shelf-life of various minimally processed foods. However, research on plasma-induced systemic degradation related to changes in chemical structure and biological activity is still very limited. In this study, the enhancement of biological activity and the mechanism of degradation of the most common type of flavonol, quercetin, induced by a dielectric barrier discharge (DBD) plasma were investigated. Quercetin is dissolved in methanol and exposed to nonthermal DBD plasma for 5, 10, 20, and 30 min. The quercetin treated with the plasma for 20 min showed rapidly increased α-glucosidase inhibitory and radical scavenging activities compared to those of parent quercetin. The structures of the degradation products 1-3 from the quercetin treated with the plasma for 20 min were isolated and characterized by interpretation of their spectroscopic data. Among the generated products, (±)-alphitonin (1) exhibited significantly improved antidiabetic and antioxidant properties compared to those of the parent quercetin. The antidiabetic and antioxidant properties were measured by α-glucosidase inhibition and 1,1-diphenyl-2-picrylhydrazyl radical scavenging assays. These results suggested that structural changes in quercetin induced by DBD plasma might be attributable to improving the biological activity.

Effect of amino acid substitution on biological activity of cyanophlyctin-β and brevinin-2R

NASA Astrophysics Data System (ADS)

Ghorani-Azam, Adel; Balali-Mood, Mahdi; Aryan, Ehsan; Karimi, Gholamreza; Riahi-Zanjani, Bamdad

2018-04-01

Antimicrobial peptides (AMPs), as ancient immune components, are found in almost all types of living organisms. They are bioactive components with strong antibacterial, antiviral, and anti-tumor properties. In this study, we designed three sequences of antimicrobial peptides to study the effects of structural changes in biological activity compared with original peptides, cyanophlyctin β, and brevinin-2R. For antibacterial activity, two Gram-positive (Staphylococcus aureus and S. epidermidis) and two Gram-negative bacteria (Escherichia coli and Pseudomonas aeroginosa) were assayed. Unlike cyanophlyctin β and brevinin-2R, the synthesized peptide (brevinin-M1, brevinin-M2 and brevinin-M3) showed no considerable antibacterial properties. Hemolytic activity of these peptides was also ignorable even at very high concentrations of 2 mg/ml. However, after proteolytic digestion by trypsin, the peptides showed antibacterial activity comparable to their original template sequences. Structural prediction suggested that the motif sequence responsible for antibacterial activity may be re-exposed to bacterial cell membrane after proteolytic digestion. Also, findings showed that only a small change in primary sequence and therefore structure of peptides may result in a significant alteration in biological activity.

GRIND2-based 3D-QSAR and prediction of activity spectra for symmetrical bis-pyridinium salts with promastigote antileishmanial activity.

PubMed

Diniz, Evelyn Mirella Lopes Pina; Tomich de Paula da Silva, Carlos Henrique; Gómez-Perez, Verónica; Federico, Leonardo Bruno; Campos Rosa, Joaquín María

2017-08-01

Leishmaniasis is a major group of neglected tropical diseases caused by the protozoan parasite Leishmania. About 12 million people are affected in 98 countries and 350 million people worldwide are at risk of infection. Current leishmaniasis treatments rely on a relatively small arsenal of drugs, including amphotericin B, pentamidine and others, which in general have some type of inconvenience. Recently, we have synthesized antileishmanial bis-pyridinium derivatives and symmetrical bis-pyridinium cyclophanes. These compounds are considered structural analogues of pentamidine, where the amidino moiety, protonated at physiological pH, is replaced by a positively charged nitrogen atom as a pyridinium ring. In this work, a statistically significant GRIND2-based 3D-QSAR model was built and biological activity predictions were in silico carried out allowing rationalization of the different activities recently obtained against Leishmania donovani (in L. donovani promastigotes) for a data set of 19 bis-pyridinium compounds. We will emphasize the most important structural requirements to improve the biological activity and probable interactions with the biological receptor as a guide for lead and prototype optimization. In addition, since no information about the actual biological target for this series of active compounds is provided, we have used Prediction of Activity Spectra for Biologically Active Substances to propose our compounds as potential nicotinic α6β3β4α5 receptor antagonists. This proposal is reinforced by the high structural similarity observed between our compounds and several anthelmintic drugs in current clinical use, which have the same drug action mechanism here predicted. Such new findings would be confirmed with further and additional experimental assays.

Computational Study on Atomic Structures, Electronic Properties, and Chemical Reactions at Surfaces and Interfaces and in Biomaterials

NASA Astrophysics Data System (ADS)

Takano, Yu; Kobayashi, Nobuhiko; Morikawa, Yoshitada

2018-06-01

Through computer simulations using atomistic models, it is becoming possible to calculate the atomic structures of localized defects or dopants in semiconductors, chemically active sites in heterogeneous catalysts, nanoscale structures, and active sites in biological systems precisely. Furthermore, it is also possible to clarify physical and chemical properties possessed by these nanoscale structures such as electronic states, electronic and atomic transport properties, optical properties, and chemical reactivity. It is sometimes quite difficult to clarify these nanoscale structure-function relations experimentally and, therefore, accurate computational studies are indispensable in materials science. In this paper, we review recent studies on the relation between local structures and functions for inorganic, organic, and biological systems by using atomistic computer simulations.

Structure-property relationship of quinuclidinium surfactants--Towards multifunctional biologically active molecules.

PubMed

Skočibušić, Mirjana; Odžak, Renata; Štefanić, Zoran; Križić, Ivana; Krišto, Lucija; Jović, Ozren; Hrenar, Tomica; Primožič, Ines; Jurašin, Darija

2016-04-01

Motivated by diverse biological and pharmacological activity of quinuclidine and oxime compounds we have synthesized and characterized novel class of surfactants, 3-hydroxyimino quinuclidinium bromides with different alkyl chains lengths (CnQNOH; n=12, 14 and 16). The incorporation of non conventional hydroxyimino quinuclidinium headgroup and variation in alkyl chain length affects hydrophilic-hydrophobic balance of surfactant molecule and thereby physicochemical properties important for its application. Therefore, newly synthesized surfactants were characterized by the combination of different experimental techniques: X-ray analysis, potentiometry, electrical conductivity, surface tension and dynamic light scattering measurements, as well as antimicrobial susceptibility tests. Comprehensive investigation of CnQNOH surfactants enabled insight into structure-property relationship i.e., way in which the arrangement of surfactant molecules in the crystal phase correlates with their solution behavior and biologically activity. The synthesized CnQNOH surfactants exhibited high adsorption efficiency and relatively low critical micelle concentrations. In addition, all investigated compounds showed very potent and promising activity against Gram-positive and clinically relevant Gram-negative bacterial strains compared to conventional antimicrobial agents: tetracycline and gentamicin. The overall results indicate that bicyclic headgroup with oxime moiety, which affects both hydrophilicity and hydrophobicity of CnQNOH molecule in addition to enabling hydrogen bonding, has dominant effect on crystal packing and physicochemical properties. The unique structural features of cationic surfactants with hydroxyimino quinuclidine headgroup along with diverse biological activity have made them promising structures in novel drug discovery. Obtained fundamental understanding how combination of different functionalities in a single surfactant molecule affects its physicochemical properties represents a good starting point for further biological research. Copyright © 2015 Elsevier B.V. All rights reserved.

Models Role within Active Learning in Biology. A Case Study

ERIC Educational Resources Information Center

Pop-Pacurar, Irina; Tirla, Felicia-Doina

2009-01-01

In order to integrate ideas and information creatively, to motivate students and activate their thinking, we have used in Biology classes a series of active methods, among which the methods of critical thinking, which had very good results. Still, in the case of some intuitive, abstract, more difficult topics, such as the cell structure,…

Biology Division progress report, October 1, 1993--September 30, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-10-01

This Progress Report summarizes the research endeavors of the Biology Division of the Oak Ridge National Laboratory during the period October 1, 1993, through September 30, 1995. The report is structured to provide descriptions of current activities and accomplishments in each of the Division`s major organizational units. Lists of information to convey the entire scope of the Division`s activities are compiled at the end of the report. Attention is focused on the following research activities: molecular, cellular, and cancer biology; mammalian genetics and development; genome mapping program; and educational activities.

Methods for the synthesis of aza(deaza)xanthines as a basis of biologically active compounds

NASA Astrophysics Data System (ADS)

Babkov, D. A.; Geisman, A. N.; Khandazhinskaya, A. L.; Novikov, M. S.

2016-03-01

The review covers methods for the synthesis of aza(deaza)xanthines, i.e., fused pyrrolo-, pyrazolo- and triazolopyrimidine heterocyclic systems, which are common core structures of various biologically active compounds. The extensive range of modern synthetic approaches is organized according to target structures and starting building blocks. The presented material is intended to benefit broad audience of specialists in the fields of organic, medicinal and pharmaceutical chemistry. The bibliography includes 195 references.

Investigating biological activity spectrum for novel quinoline analogues 2: hydroxyquinolinecarboxamides with photosynthesis-inhibiting activity.

PubMed

Musiol, Robert; Tabak, Dominik; Niedbala, Halina; Podeszwa, Barbara; Jampilek, Josef; Kralova, Katarina; Dohnal, Jiri; Finster, Jacek; Mencel, Agnieszka; Polanski, Jaroslaw

2008-04-15

Two series of amides based on quinoline scaffold were designed and synthesized in search of photosynthesis inhibitors. The compounds were tested for their photosynthesis-inhibiting activity against Spinacia oleracea L. and Chlorella vulgaris Beij. The compounds lipophilicity was determined by the RP-HPLC method. Several compounds showed biological activity similar or even higher than that of the standard (DCMU). The structure-activity relationships are discussed.

Preparation of Gc protein-derived macrophage activating factor (GcMAF) and its structural characterization and biological activities.

PubMed

Mohamad, Saharuddin Bin; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-01-01

Gc protein has been reported to be a precursor of Gc protein-derived macrophage activation factor (GcMAF) in the inflammation-primed macrophage activation cascade. An inducible beta-galactosidase of B cells and neuraminidase of T cells convert Gc protein to GcMAF. Gc protein from human serum was purified using 25(OH)D3 affinity column chromatography and modified to GcMAF using immobilized glycosidases (beta-galactosidase and neuraminidase) The sugar moiety structure of GcMAF was characterized by lectin blotting by Helix pomatia agglutinin. The biological activities of GcMAF were evaluated by a superoxide generation assay and a phagocytosis assay. We successfully purified Gc protein from human serum. GcMAF was detected by lectin blotting and showed a high biological activity. Our results support the importance of the terminal N-acetylgalactosamine moiety in the GcMAF-mediated macrophage activation cascade, and the existence of constitutive GcMAF in human serum. These preliminary data are important for designing small molecular GcMAF mimics.

Automated Inference of Chemical Discriminants of Biological Activity.

PubMed

Raschka, Sebastian; Scott, Anne M; Huertas, Mar; Li, Weiming; Kuhn, Leslie A

2018-01-01

Ligand-based virtual screening has become a standard technique for the efficient discovery of bioactive small molecules. Following assays to determine the activity of compounds selected by virtual screening, or other approaches in which dozens to thousands of molecules have been tested, machine learning techniques make it straightforward to discover the patterns of chemical groups that correlate with the desired biological activity. Defining the chemical features that generate activity can be used to guide the selection of molecules for subsequent rounds of screening and assaying, as well as help design new, more active molecules for organic synthesis.The quantitative structure-activity relationship machine learning protocols we describe here, using decision trees, random forests, and sequential feature selection, take as input the chemical structure of a single, known active small molecule (e.g., an inhibitor, agonist, or substrate) for comparison with the structure of each tested molecule. Knowledge of the atomic structure of the protein target and its interactions with the active compound are not required. These protocols can be modified and applied to any data set that consists of a series of measured structural, chemical, or other features for each tested molecule, along with the experimentally measured value of the response variable you would like to predict or optimize for your project, for instance, inhibitory activity in a biological assay or ΔG binding . To illustrate the use of different machine learning algorithms, we step through the analysis of a dataset of inhibitor candidates from virtual screening that were tested recently for their ability to inhibit GPCR-mediated signaling in a vertebrate.

Challenges in the Development of Functional Assays of Membrane Proteins

PubMed Central

Tiefenauer, Louis; Demarche, Sophie

2012-01-01

Lipid bilayers are natural barriers of biological cells and cellular compartments. Membrane proteins integrated in biological membranes enable vital cell functions such as signal transduction and the transport of ions or small molecules. In order to determine the activity of a protein of interest at defined conditions, the membrane protein has to be integrated into artificial lipid bilayers immobilized on a surface. For the fabrication of such biosensors expertise is required in material science, surface and analytical chemistry, molecular biology and biotechnology. Specifically, techniques are needed for structuring surfaces in the micro- and nanometer scale, chemical modification and analysis, lipid bilayer formation, protein expression, purification and solubilization, and most importantly, protein integration into engineered lipid bilayers. Electrochemical and optical methods are suitable to detect membrane activity-related signals. The importance of structural knowledge to understand membrane protein function is obvious. Presently only a few structures of membrane proteins are solved at atomic resolution. Functional assays together with known structures of individual membrane proteins will contribute to a better understanding of vital biological processes occurring at biological membranes. Such assays will be utilized in the discovery of drugs, since membrane proteins are major drug targets.

Purity-activity relationships of natural products: the case of anti-TB active ursolic acid.

PubMed

Jaki, Birgit U; Franzblau, Scott G; Chadwick, Lucas R; Lankin, David C; Zhang, Fangqiu; Wang, Yuehong; Pauli, Guido F

2008-10-01

The present study explores the variability of biological responses from the perspective of sample purity and introduces the concept of purity-activity relationships (PARs) in natural product research. The abundant plant triterpene ursolic acid (1) was selected as an exemplary natural product due to the overwhelming number yet inconsistent nature of its approximate 120 reported biological activities, which include anti-TB potential. Nine different samples of ursolic acid with purity certifications were obtained, and their purity was independently assessed by means of quantitative 1H NMR (qHNMR). Biological evaluation consisted of determining MICs against two strains of virulent Mycobacterium tuberculosis and IC50 values in Vero cells. Ab initio structure elucidation provided unequivocal structural confirmation and included an extensive 1H NMR spin system analysis, determination of nearly all J couplings and the complete NOE pattern, and led to the revision of earlier reports. As a net result, a sigmoid PAR profile of 1 was obtained, demonstrating the inverse correlation of purity and anti-TB bioactivity. The results imply that synergistic effects of 1 and its varying impurities are the likely cause of previously reported antimycobacterial potential. Generating PARs is a powerful extension of the routinely performed quantitative correlation of structure and activity ([Q]SAR). Advanced by the use of primary analytical methods such as qHNMR, PARs enable the elucidation of cases like 1 when increasing purity voids biological activity. This underlines the potential of PARs as a tool in drug discovery and synergy research and accentuates the need to routinely combine biological testing with purity assessment.

Supporting Representational Competence in High School Biology with Computer-Based Biomolecular Visualizations

ERIC Educational Resources Information Center

Wilder, Anna; Brinkerhoff, Jonathan

2007-01-01

This study assessed the effectiveness of computer-based biomolecular visualization activities on the development of high school biology students' representational competence as a means of understanding and visualizing protein structure/function relationships. Also assessed were students' attitudes toward these activities. Sixty-nine students…

SOD activity of carboxyfullerenes predicts their neuroprotective efficacy: A structure-activity study

PubMed Central

Ali, Sameh Saad; Hardt, Joshua I.; Dugan, Laura L.

2008-01-01

Superoxide radical anion is a biologically important oxidant that has been linked to tissue injury and inflammation in several diseases. Here we carried out a structure-activity study on 6 different carboxyfullerene superoxide dismutase (SOD) mimetics with distinct electronic and biophysical characteristics. Neurotoxicity via NMDA receptors, which involves intracellular superoxide, was used as a model to evaluate structure-activity relationships between reactivity towards superoxide and neuronal rescue by these drugs. A significant correlation between neuroprotection by carboxyfullerenes and their ki towards superoxide radical was observed. Computer-assistant molecular modeling demonstrated that the reactivity towards superoxide is sensitive to changes in dipole moment which are dictated not only by the number of carboxyl groups, but also by their distribution on the fullerene ball. These results indicate that the SOD activity of these cell-permeable compounds predicts neuroprotection, and establishes a structure-activity relationship to aid in future studies on the biology of superoxide across disciplines. PMID:18656425

Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress

PubMed Central

2015-01-01

Protein structure underlies essential biological processes and provides a blueprint for molecular mimicry that drives drug discovery. Although small molecules represent the lion’s share of agents that target proteins for therapeutic benefit, there remains no substitute for the natural properties of proteins and their peptide subunits in the majority of biological contexts. The peptide α-helix represents a common structural motif that mediates communication between signaling proteins. Because peptides can lose their shape when taken out of context, developing chemical interventions to stabilize their bioactive structure remains an active area of research. The all-hydrocarbon staple has emerged as one such solution, conferring α-helical structure, protease resistance, cellular penetrance, and biological activity upon successful incorporation of a series of design and application principles. Here, we describe our more than decade-long experience in developing stapled peptides as biomedical research tools and prototype therapeutics, highlighting lessons learned, pitfalls to avoid, and keys to success. PMID:24601557

CyBy(2): a structure-based data management tool for chemical and biological data.

PubMed

Höck, Stefan; Riedl, Rainer

2012-01-01

We report the development of a powerful data management tool for chemical and biological data: CyBy(2). CyBy(2) is a structure-based information management tool used to store and visualize structural data alongside additional information such as project assignment, physical information, spectroscopic data, biological activity, functional data and synthetic procedures. The application consists of a database, an application server, used to query and update the database, and a client application with a rich graphical user interface (GUI) used to interact with the server.

[Melatonin as a universal stabilizing factor of mental activity].

PubMed

Arushanian, Ē B

2011-01-01

Pineal hormone melatonin stabilizes mental activity of man and animals due to its somnogenic, anxiolytic, antidepressant and nootropic properties. Melatonin effects are based on the synchronization of biological rhythms via the influence on the cerebral structures which control biological rhythms and emotions and normalize endocrine and immune state.

Thermodynamic modeling of transcription: sensitivity analysis differentiates biological mechanism from mathematical model-induced effects.

PubMed

Dresch, Jacqueline M; Liu, Xiaozhou; Arnosti, David N; Ay, Ahmet

2010-10-24

Quantitative models of gene expression generate parameter values that can shed light on biological features such as transcription factor activity, cooperativity, and local effects of repressors. An important element in such investigations is sensitivity analysis, which determines how strongly a model's output reacts to variations in parameter values. Parameters of low sensitivity may not be accurately estimated, leading to unwarranted conclusions. Low sensitivity may reflect the nature of the biological data, or it may be a result of the model structure. Here, we focus on the analysis of thermodynamic models, which have been used extensively to analyze gene transcription. Extracted parameter values have been interpreted biologically, but until now little attention has been given to parameter sensitivity in this context. We apply local and global sensitivity analyses to two recent transcriptional models to determine the sensitivity of individual parameters. We show that in one case, values for repressor efficiencies are very sensitive, while values for protein cooperativities are not, and provide insights on why these differential sensitivities stem from both biological effects and the structure of the applied models. In a second case, we demonstrate that parameters that were thought to prove the system's dependence on activator-activator cooperativity are relatively insensitive. We show that there are numerous parameter sets that do not satisfy the relationships proferred as the optimal solutions, indicating that structural differences between the two types of transcriptional enhancers analyzed may not be as simple as altered activator cooperativity. Our results emphasize the need for sensitivity analysis to examine model construction and forms of biological data used for modeling transcriptional processes, in order to determine the significance of estimated parameter values for thermodynamic models. Knowledge of parameter sensitivities can provide the necessary context to determine how modeling results should be interpreted in biological systems.

Spectroscopic study of biologically active glasses

NASA Astrophysics Data System (ADS)

Szumera, M.; Wacławska, I.; Mozgawa, W.; Sitarz, M.

2005-06-01

It is known that the chemical activity phenomenon is characteristic for some inorganic glasses and they are able to participate in biological processes of living organisms (plants, animals and human bodies). An example here is the selective removal of silicate-phosphate glass components under the influence of biological solutions, which has been applied in designing glasses acting as ecological fertilizers of controlled release rate of the nutrients for plants. The structure of model silicate-phosphate glasses containing the different amounts of the glass network formers, i.e. Ca 2+ and Mg 2+, as a binding components were studied. These elements besides other are indispensable of the normal growth of plants. In order to establish the function and position occupied by the particular components in the glass structure, the glasses were examined by FTIR spectroscopy (with spectra decomposition) and XRD methods. It has been found that the increasing amount of MgO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes systematically from a structure of the cristobalite type to a structure corresponding to forsterite type. Whilst the increasing content of CaO in the structure of silicate-phosphate glasses causes the formation of domains the structure of which changes from a structure typical for cristobalite through one similar to the structure of calcium orthophosphate, to a structure corresponding to calcium silicates. The changing character of domains structure is the reason of different chemical activity of glasses.

Biology 23. Unit One -- The Cell: Structure and Physiology.

ERIC Educational Resources Information Center

Nederland Independent School District, TX.

GRADES OR AGES: Not given. SUBJECT MATTER: Biology, the structure and physiology of the cell. ORGANIZATION AND PHYSICAL APPEARANCE: There are four sections: a) objectives for the unit, b) bibliography, c) activities, and d) evaluation. The guide is directed to the student rather than the teacher. The guide is mimeographed and stapled, with no…

Synthetic and Medicinal Prospective of Structurally Modified Curcumins.

PubMed

Kumar, Bhupinder; Singh, Virender; Shankar, Ravi; Kumar, Kapil; Rawal, Ravindra K

2017-01-01

Curcumin, a natural yellow phenolic compound, is present in various types of herbs, particularly in Turmeric, Curcuma longa Linn. (Zingiberaceae family) rhizomes. Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. In the last decade curcumine and its various synthetic analogues have been prepared and evaluated for various pharmacological activities that prove it as a lead molecule against several biological targets. It is a natural antioxidant and exhibited many pharmacological activities such as anti-inflammatory, anti-microbial, anticancer, anti-Alzheimer in both preclinical and clinical studies. Moreover, Curcumin and its analogues have anti-tubercular, cardioprotective, anti-diabetic, hepatoprotective, neuroprotective, nephroprotective, antirheumatic and anti-viral activities. The substitutions of 1,6-heptadiene linkage moiety via carbonyl group sustituion and addition of heterocyclic linker; isoxazole, 1H-pyrazole, cyclopentanone, piperidin-4-one, N-methylpiperidin-4-one enhance biological activities. The structure activity relationship of various curcumin analogues is studied for medicinal purposes and it reveals that monocarbonyl linkage analogues have anticancer properties. The current review gives an insight of the history, chemistry, analogues and most interesting in vitro and in vivo studies on the biological effects of Curcumin and its analogues.

Potent μ-Opioid Receptor Agonists from Cyclic Peptides Tyr-c[D-Lys-Xxx-Tyr-Gly]: Synthesis, Biological, and Structural Evaluation.

PubMed

Li, Yangmei; Cazares, Margret; Wu, Jinhua; Houghten, Richard A; Toll, Laurence; Dooley, Colette

2016-02-11

To optimize the structure of a μ-opioid receptor ligand, analogs H-Tyr-c[D-Lys-Xxx-Tyr-Gly] were synthesized and their biological activity was tested. The analog containing a Phe(3) was identified as not only exhibiting binding affinity 14-fold higher than the original hit but also producing agonist activity 3-fold more potent than morphine. NMR study suggested that a trans conformation at D-Lys(2)-Xxx(3) is crucial for these cyclic peptides to maintain high affinity, selectivity, and functional activity toward the μ-opioid receptor.

Molecular Characteristics and Biological Functions of Surface-Active and Surfactant Proteins.

PubMed

Sunde, Margaret; Pham, Chi L L; Kwan, Ann H

2017-06-20

Many critical biological processes take place at hydrophobic:hydrophilic interfaces, and a wide range of organisms produce surface-active proteins and peptides that reduce surface and interfacial tension and mediate growth and development at these boundaries. Microorganisms produce both small lipid-associated peptides and amphipathic proteins that allow growth across water:air boundaries, attachment to surfaces, predation, and improved bioavailability of hydrophobic substrates. Higher-order organisms produce surface-active proteins with a wide variety of functions, including the provision of protective foam environments for vulnerable reproductive stages, evaporative cooling, and gas exchange across airway membranes. In general, the biological functions supported by these diverse polypeptides require them to have an amphipathic nature, and this is achieved by a diverse range of molecular structures, with some proteins undergoing significant conformational change or intermolecular association to generate the structures that are surface active.

Essential Set of Molecular Descriptors for ADME Prediction in Drug and Environmental Chemical Space

EPA Science Inventory

Historically, the disciplines of pharmacology and toxicology have embraced quantitative structure-activity relationships (QSAR) and quantitative structure-property relationships (QSPR) to predict ADME properties or biological activities of untested chemicals. The question arises ...

Effect of Thermal and Shear Stressors on the Physical Properties, Structural Integrity and Biological Activity of the Anti-TNF-alpha Monoclonal Antibody, Infliximab.

PubMed

Alsaddique, Jihad A; Pabari, Ritesh M; Ramtoola, Zebunnissa

The influence of thermal and shear stressors on the stability of the anti-TNF-α monoclonal antibody (mAb), Infliximab® (INF) was investigated. INF at concentrations of 1, 4 and 10 mg/ml was subjected to thermal stress at temperatures of 25-65°C and to shear force by sonication for 1 and 3 minutes. The stressed samples were analysed for physical properties by particle size, zeta potential, for structural integrity by gel electrophoresis (SDS-PAGE) and circular dichroism, INF content by UV spectroscopy and for biological activity by ELISA. Results show no change in physical properties or structural integrity of INF at any concentration tested, when subjected to a temperature of up to 50°C. At 65°C, aggregation and precipitation of INF was observed. When subjected to shear stress, higher concentrations of INF at 4 and 10mg/ml maintained their physical properties and structural integrity. However, the biological activity of INF was found to decrease with increasing temperature and sonication time, and was concentration dependent (ANOVA; p<0.05). Interestingly, lyophilisation of INF at 1mg/ml did not affect its physical properties, structural integrity or its biological activity. These findings have important implications with respect to pharmaceutical processing of INF and mAbs including formulation as polymeric micro and nanoparticle systems for sustained or targeted delivery. These findings also have important implications with respect to the handling and storage of INF and mAbs for clinical use.

Synthesis, characterization and biological activities of semicarbazones and their copper complexes.

PubMed

Venkatachalam, Taracad K; Bernhardt, Paul V; Noble, Chris J; Fletcher, Nicholas; Pierens, Gregory K; Thurecht, Kris J; Reutens, David C

2016-09-01

Substituted semicarbazones/thiosemicarbazones and their copper complexes have been prepared and several single crystal structures examined. The copper complexes of these semicarbazone/thiosemicarbazones were prepared and several crystal structures examined. The single crystal X-ray structure of the pyridyl-substituted semicarbazone showed two types of copper complexes, a monomer and a dimer. We also found that the p-nitrophenyl semicarbazone formed a conventional 'magic lantern' acetate-bridged dimer. Electron Paramagnetic Resonance (EPR) of several of the copper complexes was consistent with the results of single crystal X-ray crystallography. The EPR spectra of the p-nitrophenyl semicarbazone copper complex in dimethylsulfoxide (DMSO) showed the presence of two species, confirming the structural information. Since thiosemicarbazones and semicarbazones have been reported to exhibit anticancer activity, we examined the anticancer activity of several of the derivatives reported in the present study and interestingly only the thiosemicarbazone showed activity while the semicarbazones were not active indicating that introduction of sulphur atom alters the biological profile of these thiosemicarbazones. Copyright © 2016 Elsevier Inc. All rights reserved.

Animal behaviour and algal camouflage jointly structure predation and selection.

PubMed

Start, Denon

2018-05-01

Trait variation can structure interactions between individuals, thus shaping selection. Although antipredator strategies are an important component of many aquatic systems, how multiple antipredator traits interact to influence consumption and selection remains contentious. Here, I use a common larval dragonfly (Epitheca canis) and its predator (Anax junius) to test for the joint effects of activity rate and algal camouflage on predation and survival selection. I found that active and poorly camouflaged Epitheca were more likely to be consumed, and thus, survival selection favoured inactive and well-camouflaged individuals. Notably, camouflage dampened selection on activity rate, likely by reducing attack rates when Epitheca encountered a predator. Correlational selection is therefore conferred by the ecological interaction of traits, rather than by opposing selection acting on linked traits. I suggest that antipredator traits with different adaptive functions can jointly structure patterns of consumption and selection. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

PubMed Central

Kapetanovic, I.M.

2008-01-01

It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

Characterization and Comparison of the Structural Features, Immune-Modulatory and Anti-Avian Influenza Virus Activities Conferred by Three Algal Sulfated Polysaccharides

PubMed Central

Song, Lin; Chen, Xiaolin; Liu, Xiaodong; Zhang, Fubo; Hu, Linfeng; Yue, Yang; Li, Kecheng; Li, Pengcheng

2015-01-01

Three marine macroalgae, i.e., Grateloupia filicina, Ulva pertusa and Sargassum qingdaoense, were selected as the deputies of Rhodophyta, Chlorophyta and Ochrophyta for comparative analysis of the molecular structures and biological activities of sulfated polysaccharides (SP). The ratio of water-soluble polysaccharides, the monosaccharide composition and the sulfated contents of three extracted SPs were determined, and their structures were characterized by Fourier transformation infrared spectroscopy. In addition, biological activity analysis showed that all three SPs had immune-modulatory activity both in vitro and in vivo, and SPs from S. qingdaoense had the best effect. Further bioassays showed that three SPs could not only enhance the immunity level stimulated by inactivated avian influenza virus (AIV) in vivo but also significantly inhibited the activity of activated AIV (H9N2 subtype) in vitro. G. filicina SP exhibited the strongest anti-AIV activity. These results revealed the variations in structural features and bioactivities among three SPs and indicated the potential adjuvants for immune-enhancement and anti-AIV. PMID:26729137

Bringing RNA into View: RNA and Its Roles in Biology.

ERIC Educational Resources Information Center

Atkins, John F.; Ellington, Andrew; Friedman, B. Ellen; Gesteland, Raymond F.; Noller, Harry F.; Pasquale, Stephen M.; Storey, Richard D.; Uhlenbeck, Olke C.; Weiner, Alan M.

This guide presents a module for college students on ribonucleic acid (RNA) and its role in biology. The module aims to integrate the latest research and its findings into college-level biology and provide an opportunity for students to understand biological processes. Four activities are presented: (1) "RNA Structure: Tapes to Shapes"; (2) "RNA…

Recent Advances in Marine Algae Polysaccharides: Isolation, Structure, and Activities.

PubMed

Xu, Shu-Ying; Huang, Xuesong; Cheong, Kit-Leong

2017-12-13

Marine algae have attracted a great deal of interest as excellent sources of nutrients. Polysaccharides are the main components in marine algae, hence a great deal of attention has been directed at isolation and characterization of marine algae polysaccharides because of their numerous health benefits. In this review, extraction and purification approaches and chemico-physical properties of marine algae polysaccharides (MAPs) are summarized. The biological activities, which include immunomodulatory, antitumor, antiviral, antioxidant, and hypolipidemic, are also discussed. Additionally, structure-function relationships are analyzed and summarized. MAPs' biological activities are closely correlated with their monosaccharide composition, molecular weights, linkage types, and chain conformation. In order to promote further exploitation and utilization of polysaccharides from marine algae for functional food and pharmaceutical areas, high efficiency, and low-cost polysaccharide extraction and purification methods, quality control, structure-function activity relationships, and specific mechanisms of MAPs activation need to be extensively investigated.

Synthesis, structural characterization and density functional studies of ethyl 4-(biphenyl-4-yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate A non-merohedral twinned structure

NASA Astrophysics Data System (ADS)

Yıdırım, Sema Öztürk; Büyükmumcu, Zeki; Butcher, Ray J.; Çetin, Gökalp; Şimşek, Rahime; Şafak, Cihat

2018-07-01

1,4-Dihydropyridine (1,4-DHP) derivatives have the reducing effect of extracellular Ca2+ ions influx on the L-type calcium channel. Because of this effect many 1,4-DHP derivatives are potent calcium channel blockers and antihypertensive agents. The biphenyl group is present in the structures of the most biologically active compounds and thus is an important group. By introducing this moiety into the structure of various compounds, active compounds are obtained. Thus, pharmacologically active structures can be condensed with the biphenyl structure to achieve novel biologically active compounds or compounds with increased activity. In this study, to achieve an active calcium channel blocker compound, the biphenyl group was introduced into the 1,4-DHP structure. The structure of the compound is proved by IR, 1H NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic activity assays have continued and positive results have been obtained. The phenyl rings [C16-C21 and C22-C27] make dihedral angles of 84.4 (1) and 87.5 (1)°, respectively, with the 1,4-dihydropyridine ring [N1/C1/C4-C9]. In the crystal, adjacent molecules are linked by Nsbnd H … O and Csbnd H … O hydrogen bonds into chains parallel to [010].

Structure investigation of three hydrazones Schiff's bases by spectroscopic, thermal and molecular orbital calculations and their biological activities

NASA Astrophysics Data System (ADS)

Belal, Arafa A. M.; Zayed, M. A.; El-Desawy, M.; Rakha, Sh. M. A. H.

2015-03-01

Three Schiff's bases AI (2(1-hydrazonoethyl)phenol), AII (2, 4-dibromo 6-(hydrazonomethyl)phenol) and AIII (2(hydrazonomethyl)phenol) were prepared as new hydrazone compounds via condensation reactions with molar ratio (1:1) of reactants. Firstly by reaction of 2-hydroxy acetophenone solution and hydrazine hydrate; it gives AI. Secondly condensation between 3,5-dibromo-salicylaldehyde and hydrazine hydrate gives AII. Thirdly condensation between salicylaldehyde and hydrazine hydrate gives AIII. The structures of AI-AIII were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H NMR spectra, and thermal analyses (TG, DTG, and DTA). The activation thermodynamic parameters, such as, ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bond responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities have been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillissubtilies and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

Efficacy of a Meiosis Learning Module Developed for the Virtual Cell Animation Collection

ERIC Educational Resources Information Center

Goff, Eric E.; Reindl, Katie M.; Johnson, Christina; McClean, Phillip; Offerdahl, Erika G.; Schroeder, Noah L.; White, Alan R.

2017-01-01

Recent reports calling for change in undergraduate biology education have resulted in the redesign of many introductory biology courses. Reports on one common change to course structure, the active-learning environment, have placed an emphasis on student preparation, noting that the positive outcomes of active learning in the classroom depend…

Bioactive terpenes from marine-derived fungi.

PubMed

Elissawy, Ahmed M; El-Shazly, Mohamed; Ebada, Sherif S; Singab, AbdelNasser B; Proksch, Peter

2015-04-03

Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years' reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

Career Education Resource Guide for Biology. Working Draft.

ERIC Educational Resources Information Center

Louisiana State Dept. of Education, Baton Rouge.

The resource guide integrates learning activities in biological science with an exploration of careers in biology or related fields. The materials are divided into seven units: tools of the scientist, basis for life, diversity (protists, plants, animals), structure and function, continuity (reproduction, development, and genetics), evolution, and…

Generation and Biological Activities of Oxidized Phospholipids

PubMed Central

Oskolkova, Olga V.; Birukov, Konstantin G.; Levonen, Anna-Liisa; Binder, Christoph J.; Stöckl, Johannes

2010-01-01

Abstract Glycerophospholipids represent a common class of lipids critically important for integrity of cellular membranes. Oxidation of esterified unsaturated fatty acids dramatically changes biological activities of phospholipids. Apart from impairment of their structural function, oxidation makes oxidized phospholipids (OxPLs) markers of “modified-self” type that are recognized by soluble and cell-associated receptors of innate immunity, including scavenger receptors, natural (germ line-encoded) antibodies, and C-reactive protein, thus directing removal of senescent and apoptotic cells or oxidized lipoproteins. In addition, OxPLs acquire novel biological activities not characteristic of their unoxidized precursors, including the ability to regulate innate and adaptive immune responses. Effects of OxPLs described in vitro and in vivo suggest their potential relevance in different pathologies, including atherosclerosis, acute inflammation, lung injury, and many other conditions. This review summarizes current knowledge on the mechanisms of formation, structures, and biological activities of OxPLs. Furthermore, potential applications of OxPLs as disease biomarkers, as well as experimental therapies targeting OxPLs, are described, providing a broad overview of an emerging class of lipid mediators. Antioxid. Redox Signal. 12, 1009–1059. PMID:19686040

Introducing Bond-Line Organic Structures in High School Biology: An Activity that Incorporates Pleasant-Smelling Molecules

ERIC Educational Resources Information Center

Rios, Andro C.; French, Gerald

2011-01-01

Chemical education occurs in settings other than just the chemistry classroom. High school biology courses are frequently where students are introduced to organic molecules and their importance to cellular chemistry. However, structural representations are often intimidating because students have not been introduced to the language. As part of a…

Synthesis, investigation of the new derivatives of dihydropyrimidines and determination of their biological activity

NASA Astrophysics Data System (ADS)

Maharramov, A. M.; Ramazanov, M. A.; Guliyeva, G. A.; Huseynzada, A. E.; Hasanova, U. A.; Shikhaliyev, N. G.; Eyvazova, G. M.; Hajiyeva, S. F.; Mamedov, I. G.; Aghayev, M. M.

2017-08-01

We reported of synthesis and investigation of the new biologically active derivatives of dihydropyrimidines 2 and 3. The investigation of structures of compounds by various experiments of NMR spectroscopy revealed the splitting of the signals to doublets and multiplets that confirms the presence of diastereomers in solution of compound 2 and the presence of diastereomers and tautomers in solution of compound 3. The individual diastereomer of compound 3 has been isolated. Biological activity of the synthesized compounds was studied on various species of genus Aspergillus fungi.

Synthesis of potent G-quadruplex binders of macrocyclic heptaoxazole and evaluation of their activities.

PubMed

Tera, Masayuki; Iida, Keisuke; Shin-ya, Kazuo; Nagasawa, Kazuo

2009-01-01

Guanine-rich DNA sequences form unique three-dimensional conformation known as G-quadruplexes (G-q). G-q structures have been found in telomere and in some oncogene promoter. Recently, it was suggested that G-q showed some biological activities including telomere shortening and transcriptional regulation. In this paper, we synthesized selective G-q binders and evaluated of their biological activities.

Sesterterpenes as tubulin tyrosine ligase inhibitors. First insight of structure-activity relationships and discovery of new lead.

PubMed

Dal Piaz, Fabrizio; Vassallo, Antonio; Lepore, Laura; Tosco, Alessandra; Bader, Ammar; De Tommasi, Nunziatina

2009-06-25

Twenty-four new sesterterpenes, compounds 1-24, were isolated from the aerial parts of Salvia dominica. Their structures were elucidated by 1D and 2D NMR experiments as well as ESIMS analysis and chemical methods. The evaluation of the biological activity of Salvia dominica sesterterpenes by means of a panel of chemical and biological approaches, including chemical proteomics, surface plasmon resonance (SPR) measurements, and biochemical assays were realized. Obtained results showed that 18 out of the 24 sesterterpene lactones isolated from Salvia dominica interact with tubulin-tyrosine ligase (TTL) an enzyme involved in the tyrosination cycle of the C-terminal of tubulin, and inhibit TTL activity in cancer cells. Besides, results of our studies provided an activity/structure relationship that can be used to design effective TTL inhibitors.

Novel Carbonyl Analogues of Tamoxifen: Design, Synthesis, and Biological Evaluation

NASA Astrophysics Data System (ADS)

Kasiotis, Konstantinos M.; Lambrinidis, George; Fokialakis, Nikolas; Tzanetou, Evangelia N.; Mikros, Emmanuel; Haroutounian, Serkos A.

2017-09-01

Aim of this work was to provide tamoxifen analogues with enhanced estrogen receptor binding affinity. Hence, several derivatives were prepared using an efficient triarylethylenes synthetic protocol. The novel compounds bioactivity was evaluated through the determination of their receptor binding affinity and their agonist/antagonist activity against breast cancer tissue using a MCF-7 cell-based assay. Phenyl esters 6a,b and 8a,b exhibited binding affinity to both ERα and ERβ higher than 4-hydroxytamoxifen while compounds 13 and 14 have shown cellular antiestrogenic activity similar to 4-hydroxytamoxifen and the known estrogen receptor inhibitor ICI182,780. Theoretical calculations and molecular modelling were applied to investigate, support and explain the biological profile of the new compounds. The relevant data indicated an agreement between calculations and demonstrated biological activity allowing to extract useful structure-activity relationships. Results herein underline that modifications of tamoxifen structure still provide molecules with substantial activity, as portrayed in the inhibition of MCF-7 cells proliferation.

Marine natural flavonoids: chemistry and biological activities.

PubMed

Martins, Beatriz T; Correia da Silva, Marta; Pinto, Madalena; Cidade, Honorina; Kijjoa, Anake

2018-05-04

As more than 70% of the world's surface is covered by oceans, marine organisms offer a rich and unlimited resource of structurally diverse bioactive compounds. These organisms have developed unique properties and bioactive compounds that are, in majority of them, unparalleled by their terrestrial counterparts due to the different surrounding ecological systems. Marine flavonoids have been extensively studied in the last decades due to a growing interest concerning their promising biological/pharmacological activities. The most common classes of marine flavonoids are flavones and flavonols, which are mostly isolated from marine plants. Although most of flavonoids are hydroxylated and methoxylated, some marine flavonoids possess an unusual substitution pattern, not commonly found in terrestrial organisms, namely the presence of sulphate, chlorine, and amino groups. This review presents, for the first time in a systematic way, the structure, natural occurrence, and biological activities of marine flavonoids.

Emergent mechanics of biological structures

PubMed Central

Dumont, Sophie; Prakash, Manu

2014-01-01

Mechanical force organizes life at all scales, from molecules to cells and tissues. Although we have made remarkable progress unraveling the mechanics of life's individual building blocks, our understanding of how they give rise to the mechanics of larger-scale biological structures is still poor. Unlike the engineered macroscopic structures that we commonly build, biological structures are dynamic and self-organize: they sculpt themselves and change their own architecture, and they have structural building blocks that generate force and constantly come on and off. A description of such structures defies current traditional mechanical frameworks. It requires approaches that account for active force-generating parts and for the formation of spatial and temporal patterns utilizing a diverse array of building blocks. In this Perspective, we term this framework “emergent mechanics.” Through examples at molecular, cellular, and tissue scales, we highlight challenges and opportunities in quantitatively understanding the emergent mechanics of biological structures and the need for new conceptual frameworks and experimental tools on the way ahead. PMID:25368421

Preparation and characterization of new biologically active polyurethane foams.

PubMed

Savelyev, Yuri; Veselov, Vitali; Markovskaya, Ludmila; Savelyeva, Olga; Akhranovich, Elena; Galatenko, Natalya; Robota, Ludmila; Travinskaya, Tamara

2014-12-01

Biologically active polyurethane foams are the fast-developed alternative to many applications of biomedical materials. Due to the polyurethane structure features and foam technology it is possible to incorporate into their structure the biologically active compounds of target purpose via structural-chemical modification of macromolecule. A series of new biologically active polyurethane foams (PUFs) was synthesized with polyethers (MM 2500-5000), polyesters MM (500-2200), 2,4(2,6) toluene diisocyanate, water as a foaming agent, catalysts, foam stabilizers and functional compounds. Different functional compounds: 1,4-di-N-oxy-2,3-bis-(oxymethyl)-quinoxaline (DOMQ), partial sodium salt of poly(acrylic acid) and 2,6-dimethyl-N,N-diethyl aminoacetatanilide hydrochloride were incorporated into the polymer structure/composition due to the chemical and/or physical bonding. Structural peculiarities of PUFs were studied by FTIR spectroscopy and X-ray scattering. Self-adhesion properties of PUFs were estimated by measuring of tensile strength at break of adhesive junction. The optical microscopy method was performed for the PUF morphology studies. Toxicological estimation of the PUFs was carried out in vitro and in vivo. The antibacterial action towards the Gram-positive and Gram-negative bacteria (Escherichia coli ATC 25922, E. coli ATC 2150, Klebsiella pneumoniae 6447, Staphylococcus aureus 180, Pseudomonas aeruginosa 8180, Proteus mirabilis F 403, P. mirabilis 6054, and Proteus vulgaris 8718) was studied by the disc method on the solid nutrient. Physic-chemical properties of the PUFs (density, tensile strength and elongation at break, water absorption and vapor permeability) showed that all studied PUFs are within the operational requirements for such materials and represent fine-cellular foams. Spectral studies confirmed the incorporation of DOMQ into the PUF's macrochain. PUFs are characterized by microheterogeneous structure. They are antibacterially active, non-toxic materials with high affinity to the tissue body, self-adhesive properties and local anesthetic effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Exploring Contemporary Issues in Genetics & Society: Karyotyping, Biological Sex, & Gender

ERIC Educational Resources Information Center

Brown, Julie C.

2013-01-01

In this two-part activity, high school biology students examine human karyotyping, sex-chromosome-linked disorders, and the relationship between biological sex and gender. Through interactive simulations and a structured discussion lab, students create a human karyotype and diagnose chromosomal disorders in hypothetical patients, as well as…

Screening For Inhibitors Of Essential Leishmania Glucose Transporters

DTIC Science & Technology

2011-07-01

of biological activities and structural diversity. The library was screened in duplicate employing 13 384-well plates. High, Med, and Low control... Antimalarial drug therapy: the role of parasite biology and drug resis- tance. J Clin Pharmacol 2006;46(12):1487–97. [3] Matovu E, Seebeck T, Enyaru JC...biological activities . Chem Pharm Bull (Tokyo) 1987;35(7):2894–9. 20] Ter Kuile BH, Opperdoes FR. A chemostat study on proline uptake and metabolism of

Activated Biological Filters (ABF Towers). Student Manual. Biological Treatment Process Control.

ERIC Educational Resources Information Center

Wooley, John F.

This student manual contains textual material for a two-lesson unit on activated bio-filters (ABF). The first lesson (the sewage treatment plant) examines those process units that are unique to the ABF system. The lesson includes a review of the structural components of the ABF system and their functions and a discussion of several operational…

Metal-containing Complexes of Lactams, Imidazoles, and Benzimidazoles and Their Biological Activity

NASA Astrophysics Data System (ADS)

Kukalenko, S. S.; Bovykin, B. A.; Shestakova, S. I.; Omel'chenko, A. M.

1985-07-01

The results of the latest investigations of the problem of the synthesis of metal-containing complexes of lactams, imidazoles, and benzimidazoles, their structure, and their stability in solutions are surveyed. Some data on their biological activity (pesticide and pharmacological) and the mechanism of their physiological action are presented. The bibliography includes 190 references.

Diversity of Secondary Metabolites from Marine Bacillus Species: Chemistry and Biological Activity

PubMed Central

Mondol, Muhammad Abdul Mojid; Shin, Hee Jae; Islam, Mohammad Tofazzal

2013-01-01

Marine Bacillus species produce versatile secondary metabolites including lipopeptides, polypeptides, macrolactones, fatty acids, polyketides, and isocoumarins. These structurally diverse compounds exhibit a wide range of biological activities, such as antimicrobial, anticancer, and antialgal activities. Some marine Bacillus strains can detoxify heavy metals through reduction processes and have the ability to produce carotenoids. The present article reviews the chemistry and biological activities of secondary metabolites from marine isolates. Side by side, the potential for application of these novel natural products from marine Bacillus strains as drugs, pesticides, carotenoids, and tools for the bioremediation of heavy metal toxicity are also discussed. PMID:23941823

Increased Course Structure Improves Performance in Introductory Biology

PubMed Central

Freeman, Scott; Haak, David; Wenderoth, Mary Pat

2011-01-01

We tested the hypothesis that highly structured course designs, which implement reading quizzes and/or extensive in-class active-learning activities and weekly practice exams, can lower failure rates in an introductory biology course for majors, compared with low-structure course designs that are based on lecturing and a few high-risk assessments. We controlled for 1) instructor effects by analyzing data from quarters when the same instructor taught the course, 2) exam equivalence with new assessments called the Weighted Bloom's Index and Predicted Exam Score, and 3) student equivalence using a regression-based Predicted Grade. We also tested the hypothesis that points from reading quizzes, clicker questions, and other “practice” assessments in highly structured courses inflate grades and confound comparisons with low-structure course designs. We found no evidence that points from active-learning exercises inflate grades or reduce the impact of exams on final grades. When we controlled for variation in student ability, failure rates were lower in a moderately structured course design and were dramatically lower in a highly structured course design. This result supports the hypothesis that active-learning exercises can make students more skilled learners and help bridge the gap between poorly prepared students and their better-prepared peers. PMID:21633066

Increased course structure improves performance in introductory biology.

PubMed

Freeman, Scott; Haak, David; Wenderoth, Mary Pat

2011-01-01

We tested the hypothesis that highly structured course designs, which implement reading quizzes and/or extensive in-class active-learning activities and weekly practice exams, can lower failure rates in an introductory biology course for majors, compared with low-structure course designs that are based on lecturing and a few high-risk assessments. We controlled for 1) instructor effects by analyzing data from quarters when the same instructor taught the course, 2) exam equivalence with new assessments called the Weighted Bloom's Index and Predicted Exam Score, and 3) student equivalence using a regression-based Predicted Grade. We also tested the hypothesis that points from reading quizzes, clicker questions, and other "practice" assessments in highly structured courses inflate grades and confound comparisons with low-structure course designs. We found no evidence that points from active-learning exercises inflate grades or reduce the impact of exams on final grades. When we controlled for variation in student ability, failure rates were lower in a moderately structured course design and were dramatically lower in a highly structured course design. This result supports the hypothesis that active-learning exercises can make students more skilled learners and help bridge the gap between poorly prepared students and their better-prepared peers.

Using Theoretical Descriptions in Structure Activity Relations. 3. Electronic Descriptors

DTIC Science & Technology

1988-08-01

Activity Relationships (QSAR) have been used successfully in the past to develop predictive equations for several biological and physical properties...Linear Free Energy Relationships (,FF.3) and is based on work by Hammet in which he derived electronic descriptors for the dissociation of substituted...structure of a compound and its activity in a system. Several different structural descriptors have been used in QSAR equations . These range from

Active matter at the interface between materials science and cell biology

NASA Astrophysics Data System (ADS)

Needleman, Daniel; Dogic, Zvonimir

2017-09-01

The remarkable processes that characterize living organisms, such as motility, self-healing and reproduction, are fuelled by a continuous injection of energy at the microscale. The field of active matter focuses on understanding how the collective behaviours of internally driven components can give rise to these biological phenomena, while also striving to produce synthetic materials composed of active energy-consuming components. The synergistic approach of studying active matter in both living cells and reconstituted systems assembled from biochemical building blocks has the potential to transform our understanding of both cell biology and materials science. This methodology can provide insight into the fundamental principles that govern the dynamical behaviours of self-organizing subcellular structures, and can lead to the design of artificial materials and machines that operate away from equilibrium and can thus attain life-like properties. In this Review, we focus on active materials made of cytoskeletal components, highlighting the role of active stresses and how they drive self-organization of both cellular structures and macroscale materials, which are machines powered by nanomachines.

Mannich bases in medicinal chemistry and drug design.

PubMed

Roman, Gheorghe

2015-01-07

The biological activity of Mannich bases, a structurally heterogeneous class of chemical compounds that are generated from various substrates through the introduction of an aminomethyl function by means of the Mannich reaction, is surveyed, with emphasis on the relationship between structure and biological activity. The review covers extensively the literature reports that have disclosed Mannich bases as anticancer and cytotoxic agents, or compounds with potential antibacterial and antifungal activity in the last decade. The most relevant studies on the activity of Mannich bases as antimycobacterial agents, antimalarials, or antiviral candidates have been included as well. The review contains also a thorough coverage of anticonvulsant, anti-inflammatory, analgesic and antioxidant activities of Mannich bases. In addition, several minor biological activities of Mannich bases, such as their ability to regulate blood pressure or inhibit platelet aggregation, their antiparasitic and anti-ulcer effects, as well as their use as agents for the treatment of mental disorders have been presented. The review gives in the end a brief overview of the potential of Mannich bases as inhibitors of various enzymes or ligands for several receptors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Anthraquinones and Derivatives from Marine-Derived Fungi: Structural Diversity and Selected Biological Activities

PubMed Central

Fouillaud, Mireille; Venkatachalam, Mekala; Girard-Valenciennes, Emmanuelle; Caro, Yanis; Dufossé, Laurent

2016-01-01

Anthraquinones and their derivatives constitute a large group of quinoid compounds with about 700 molecules described. They are widespread in fungi and their chemical diversity and biological activities recently attracted attention of industries in such fields as pharmaceuticals, clothes dyeing, and food colorants. Their positive and/or negative effect(s) due to the 9,10-anthracenedione structure and its substituents are still not clearly understood and their potential roles or effects on human health are today strongly discussed among scientists. As marine microorganisms recently appeared as producers of an astonishing variety of structurally unique secondary metabolites, they may represent a promising resource for identifying new candidates for therapeutic drugs or daily additives. Within this review, we investigate the present knowledge about the anthraquinones and derivatives listed to date from marine-derived filamentous fungi′s productions. This overview highlights the molecules which have been identified in microorganisms for the first time. The structures and colors of the anthraquinoid compounds come along with the known roles of some molecules in the life of the organisms. Some specific biological activities are also described. This may help to open doors towards innovative natural substances. PMID:27023571

System among the corticosteroids: specificity and molecular dynamics

PubMed Central

Brookes, Jennifer C.; Galigniana, Mario D.; Harker, Anthony H.; Stoneham, A. Marshall; Vinson, Gavin P.

2012-01-01

Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand–receptor interactions. PMID:21613285

Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors.

PubMed

Li, Xiao; Lu, Xueyi; Chen, Wenmin; Liu, Huiqing; Zhan, Peng; Pannecouque, Christophe; Balzarini, Jan; De Clercq, Erik; Liu, Xinyong

2014-10-01

A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antifungal plant defensins: increased insight in their mode of action as a basis for their use to combat fungal infections.

PubMed

Cools, Tanne L; Struyfs, Caroline; Cammue, Bruno Pa; Thevissen, Karin

2017-04-01

Plant defensins are small, cationic peptides with a highly conserved 3D structure. They have been studied extensively in the past decades. Various biological activities have been attributed to plant defensins, such as anti-insect and antimicrobial activities, but they are also known to affect ion channels and display antitumor activity. This review focuses on the structure, biological activity and antifungal mode of action of some well-characterized plant defensins, with particular attention to their fungal membrane target(s), their induced cell death mechanisms as well as their antibiofilm activity. As plant defensins are, in general, not toxic to human cells, show in vivo efficacy and have low frequencies of resistance occurrence, they are of particular interest in the fight against fungal infections.

Pharmacological activities of a new glycosaminoglycan, acharan sulfate isolated from the giant African snail Achatina fulica.

PubMed

Shim, Jin Young; Lee, Yeon Sil; Jung, Sang Hoon; Choi, Hyung Seok; Shin, Kuk Hyun; Kim, Yeong Shik

2002-12-01

Acharan sulfate (AS) is a glycosaminoglycan (GAG) prepared from the giant African snail, Achatina fulica. In this study, some biological activities of AS were evaluated on the basis of structural similarities to heparin/heparan sulfate and the biological functions of GAGs. We demonstrated that it exhibited strong immunostimulating activities as measured by carbon clearance test in mice and in vivo phagocytosis. It also exhibited a significant hypoglycemic activity in epinephrine (EP)-induced hyperglycemia as well as antifatigue effects by weight-loaded forced swimming test. And it showed hypolipidemic activities in cholesterol-rich mixture induced hyperlipidemia in rats. The above results indicate that AS has diverse biological activities and suggest therapeutically important target molecules.

Total synthesis and structure-activity investigation of the marine natural product neopeltolide.

PubMed

Custar, Daniel W; Zabawa, Thomas P; Hines, John; Crews, Craig M; Scheidt, Karl A

2009-09-02

The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action.

PubMed

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens.

Combining QSAR Modeling and Text-Mining Techniques to Link Chemical Structures and Carcinogenic Modes of Action

PubMed Central

Papamokos, George; Silins, Ilona

2016-01-01

There is an increasing need for new reliable non-animal based methods to predict and test toxicity of chemicals. Quantitative structure-activity relationship (QSAR), a computer-based method linking chemical structures with biological activities, is used in predictive toxicology. In this study, we tested the approach to combine QSAR data with literature profiles of carcinogenic modes of action automatically generated by a text-mining tool. The aim was to generate data patterns to identify associations between chemical structures and biological mechanisms related to carcinogenesis. Using these two methods, individually and combined, we evaluated 96 rat carcinogens of the hematopoietic system, liver, lung, and skin. We found that skin and lung rat carcinogens were mainly mutagenic, while the group of carcinogens affecting the hematopoietic system and the liver also included a large proportion of non-mutagens. The automatic literature analysis showed that mutagenicity was a frequently reported endpoint in the literature of these carcinogens, however, less common endpoints such as immunosuppression and hormonal receptor-mediated effects were also found in connection with some of the carcinogens, results of potential importance for certain target organs. The combined approach, using QSAR and text-mining techniques, could be useful for identifying more detailed information on biological mechanisms and the relation with chemical structures. The method can be particularly useful in increasing the understanding of structure and activity relationships for non-mutagens. PMID:27625608

Pyramidal neurovision architecture for vision machines

NASA Astrophysics Data System (ADS)

Gupta, Madan M.; Knopf, George K.

1993-08-01

The vision system employed by an intelligent robot must be active; active in the sense that it must be capable of selectively acquiring the minimal amount of relevant information for a given task. An efficient active vision system architecture that is based loosely upon the parallel-hierarchical (pyramidal) structure of the biological visual pathway is presented in this paper. Although the computational architecture of the proposed pyramidal neuro-vision system is far less sophisticated than the architecture of the biological visual pathway, it does retain some essential features such as the converging multilayered structure of its biological counterpart. In terms of visual information processing, the neuro-vision system is constructed from a hierarchy of several interactive computational levels, whereupon each level contains one or more nonlinear parallel processors. Computationally efficient vision machines can be developed by utilizing both the parallel and serial information processing techniques within the pyramidal computing architecture. A computer simulation of a pyramidal vision system for active scene surveillance is presented.

Effects of various pretreatments on biological sulfate reduction with waste activated sludge as electron donor and waste activated sludge diminution under biosulfidogenic condition.

PubMed

Sheng, Yuxing; Cao, Hongbin; Li, Yuping; Zhang, Yi

2010-07-15

The current study focused on the influences of various pretreatments, including alkaline, ultrasonic and thermal pretreatments on biological sulfate reduction with waste activated sludge (WAS) as sole electron donor. Our results showed that thermal and ultrasonic pretreatments increased the sulfate reduction percentage by 14.8% and 7.1%, respectively, compared with experiment with raw WAS, while alkaline pretreatment decreased the sulfate reduction percentage by 46%. By analyzing the WAS structure, particle size distribution, organic component, and enzyme activity after different pretreatments, we studied the effects of these pretreatments on WAS as well as on the mechanisms of how biological sulfate reduction was affected. The reduction of WAS and variation of WAS structure in the process of sulfate reduction were investigated. Our results showed that biosulfidogenesis was an efficient method of diminishing WAS, and various pretreatments could enhance the reduction efficiency of volatile solid in the WAS. 2010 Elsevier B.V. All rights reserved.

Marine Rare Actinobacteria: Isolation, Characterization, and Strategies for Harnessing Bioactive Compounds

PubMed Central

Dhakal, Dipesh; Pokhrel, Anaya Raj; Shrestha, Biplav; Sohng, Jae Kyung

2017-01-01

Actinobacteria are prolific producers of thousands of biologically active natural compounds with diverse activities. More than half of these bioactive compounds have been isolated from members belonging to actinobacteria. Recently, rare actinobacteria existing at different environmental settings such as high altitudes, volcanic areas, and marine environment have attracted attention. It has been speculated that physiological or biochemical pressures under such harsh environmental conditions can lead to the production of diversified natural compounds. Hence, marine environment has been focused for the discovery of novel natural products with biological potency. Many novel and promising bioactive compounds with versatile medicinal, industrial, or agricultural uses have been isolated and characterized. The natural compounds cannot be directly used as drug or other purposes, so they are structurally modified and diversified to ameliorate their biological or chemical properties. Versatile synthetic biological tools, metabolic engineering techniques, and chemical synthesis platform can be used to assist such structural modification. This review summarizes the latest studies on marine rare actinobacteria and their natural products with focus on recent approaches for structural and functional diversification of such microbial chemicals for attaining better applications. PMID:28663748

Spectroscopic characteristic (FT-IR, FT-Raman, UV, 1H and 13C NMR), theoretical calculations and biological activity of alkali metal homovanillates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Kowczyk-Sadowy, M.; Piekut, J.; Regulska, E.; Lewandowski, W.

2016-04-01

The structural and vibrational properties of lithium, sodium, potassium, rubidium and cesium homovanillates were investigated in this paper. Supplementary molecular spectroscopic methods such as: FT-IR, FT-Raman in the solid phase, UV and NMR were applied. The geometrical parameters and energies were obtained from density functional theory (DFT) B3LYP method with 6-311++G** basis set calculations. The geometry of the molecule was fully optimized, vibrational spectra were calculated and fundamental vibrations were assigned. Geometric and magnetic aromaticity indices, atomic charges, dipole moments, HOMO and LUMO energies were also calculated. The microbial activity of investigated compounds was tested against Bacillus subtilis (BS), Pseudomonas aeruginosa (PA), Escherichia coli (EC), Staphylococcus aureus (SA) and Candida albicans (CA). The relationship between the molecular structure of tested compounds and their antimicrobial activity was studied. The principal component analysis (PCA) was applied in order to attempt to distinguish the biological activities of these compounds according to selected band wavenumbers. Obtained data show that the FT-IR spectra can be a rapid and reliable analytical tool and a good source of information for the quantitative analysis of the relationship between the molecular structure of the compound and its biological activity.

Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado).

PubMed

Konno, K; Hisada, M; Naoki, H; Itagaki, Y; Kawai, N; Miwa, A; Yasuhara, T; Morimoto, Y; Nakata, Y

2000-11-01

A new mast cell degranulating peptide, eumenine mastoparan-AF (EMP-AF), was isolated from the venom of the solitary wasp Anterhynchium flavomarginatum micado, the most common eumenine wasp found in Japan. The structure was analyzed by FAB-MS/MS together with Edman degradation, which was corroborated by solid-phase synthesis. The sequence of EMP-AF, Ile-Asn-Leu-Leu-Lys-Ile-Ala-Lys-Gly-Ile-Ile-Lys-Ser-Leu-NH(2), was similar to that of mastoparan, a mast cell degranulating peptide from a hornet venom; tetradecapeptide with C-terminus amidated and rich in hydrophobic and basic amino acids. In fact, EMP-AF exhibited similar activity to mastoparan in stimulating degranulation from rat peritoneal mast cells and RBL-2H3 cells. It also showed significant hemolytic activity in human erythrocytes. Therefore, this is the first example that a mast cell degranulating peptide is found in the solitary wasp venom. Besides the degranulation and hemolytic activity, EMP-AF also affects on neuromuscular transmission in the lobster walking leg preparation. Three analogs EMP-AF-1 approximately 3 were snythesized and biologically tested together with EMP-AF, resulting in the importance of the C-terminal amide structure for biological activities.

Spectroscopy of Isolated Prebiotic Nucleobases

NASA Technical Reports Server (NTRS)

Svadlenak, Nathan; Callahan, Michael P.; Ligare, Marshall; Gulian, Lisa; Gengeliczki, Zsolt; Nachtigallova, Dana; Hobza, Pavel; deVries, Mattanjah

2011-01-01

We use multiphoton ionization and double resonance spectroscopy to study the excited state dynamics of biologically relevant molecules as well as prebiotic nucleobases, isolated in the gas phase. Molecules that are biologically relevant to life today tend to exhibit short excited state lifetimes compared to similar but non-biologically relevant analogs. The mechanism is internal conversion, which may help protect the biologically active molecules from UV damage. This process is governed by conical intersections that depend very strongly on molecular structure. Therefore we have studied purines and pyrimidines with systematic variations of structure, including substitutions, tautomeric forms, and cluster structures that represent different base pair binding motifs. These structural variations also include possible alternate base pairs that may shed light on prebiotic chemistry. With this in mind we have begun to probe the ultrafast dynamics of molecules that exhibit very short excited states and search for evidence of internal conversions.

Chalcones: structural requirements for antioxidant, estrogenic and antiproliferative activities.

PubMed

Calliste, C A; Le Bail, J C; Trouillas, P; Pouget, C; Habrioux, G; Chulia, A J; Duroux, J L

2001-01-01

Flavonoids are largely studied for their biological properties and particularly for their scavenging and antioxidant activities. In the present study, we first evaluated the antioxidant and the estrogenic actions of chalcones, then we tested their effects on MCF-7 cell proliferation. Chalcones are unique in the flavonoids family in lacking a heterocyclic C ring. We tested substituted chalcones with different numbers and different positions of the hydroxy groups: 2'-hydroxychalcone, 4'-hydroxychalcone, 4-hydroxychalcone, 2',4-dihydroxychalcone, isoliquiritigenin, 2',4'-dihydroxychalcone, phloretin and naringenin chalcone. For the antioxidant tests we established the importance of the alpha-beta double bond and the 6'-hydroxy group. The establishment of the structure-activity relationship for the estrogenic properties showed a correlation between the antioxidant and the estrogenic properties. The importance of conformation and hydroxy group positions observed for chalcones, having antioxidant and estrogenic properties, was also observed on MCF-7 cell growth with the same structure-activity relationship. The role of electron and hydrogen transfer in the correlation between these three biological activities was discussed.

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

PubMed

Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

2013-07-01

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Review on Abyssomicins: Inhibitors of the Chorismate Pathway and Folate Biosynthesis.

PubMed

Sadaka, Carmen; Ellsworth, Edmund; Hansen, Paul Robert; Ewin, Richard; Damborg, Peter; Watts, Jeffrey L

2018-06-06

Antifolates targeting folate biosynthesis within the shikimate-chorismate-folate metabolic pathway are ideal and selective antimicrobials, since higher eukaryotes lack this pathway and rely on an exogenous source of folate. Resistance to the available antifolates, inhibiting the folate pathway, underlines the need for novel antibiotic scaffolds and molecular targets. While para-aminobenzoic acid synthesis within the chorismate pathway constitutes a novel molecular target for antifolates, abyssomicins are its first known natural inhibitors. This review describes the abyssomicin family, a novel spirotetronate polyketide Class I antimicrobial. It summarizes synthetic and biological studies, structural, biosynthetic, and biological properties of the abyssomicin family members. This paper aims to explain their molecular target, mechanism of action, structure⁻activity relationship, and to explore their biological and pharmacological potential. Thirty-two natural abyssomicins and numerous synthetic analogues have been reported. The biological activity of abyssomicins includes their antimicrobial activity against Gram-positive bacteria and mycobacteria, antitumor properties, latent human immunodeficiency virus (HIV) reactivator, anti-HIV and HIV replication inducer properties. Their antimalarial properties have not been explored yet. Future analoging programs using the structure⁻activity relationship data and synthetic approaches may provide a novel abyssomicin structure that is active and devoid of cytotoxicity. Abyssomicin J and atrop- o -benzyl-desmethylabyssomicin C constitute promising candidates for such programs.

Nonlinear signaling on biological networks: The role of stochasticity and spectral clustering

NASA Astrophysics Data System (ADS)

Hernandez-Hernandez, Gonzalo; Myers, Jesse; Alvarez-Lacalle, Enrique; Shiferaw, Yohannes

2017-03-01

Signal transduction within biological cells is governed by networks of interacting proteins. Communication between these proteins is mediated by signaling molecules which bind to receptors and induce stochastic transitions between different conformational states. Signaling is typically a cooperative process which requires the occurrence of multiple binding events so that reaction rates have a nonlinear dependence on the amount of signaling molecule. It is this nonlinearity that endows biological signaling networks with robust switchlike properties which are critical to their biological function. In this study we investigate how the properties of these signaling systems depend on the network architecture. Our main result is that these nonlinear networks exhibit bistability where the network activity can switch between states that correspond to a low and high activity level. We show that this bistable regime emerges at a critical coupling strength that is determined by the spectral structure of the network. In particular, the set of nodes that correspond to large components of the leading eigenvector of the adjacency matrix determines the onset of bistability. Above this transition the eigenvectors of the adjacency matrix determine a hierarchy of clusters, defined by its spectral properties, which are activated sequentially with increasing network activity. We argue further that the onset of bistability occurs either continuously or discontinuously depending upon whether the leading eigenvector is localized or delocalized. Finally, we show that at low network coupling stochastic transitions to the active branch are also driven by the set of nodes that contribute more strongly to the leading eigenvector. However, at high coupling, transitions are insensitive to network structure since the network can be activated by stochastic transitions of a few nodes. Thus this work identifies important features of biological signaling networks that may underlie their biological function.

The activation of fibroblast growth factors (FGFs) by glycosaminoglycans: influence of the sulfation pattern on the biological activity of FGF-1.

PubMed

Angulo, Jesús; Ojeda, Rafael; de Paz, José-Luis; Lucas, Ricardo; Nieto, Pedro M; Lozano, Rosa M; Redondo-Horcajo, Mariano; Giménez-Gallego, Guillermo; Martín-Lomas, Manuel

2004-01-03

Six synthetic heparin-like oligosaccharides have been used to investigate the effect of the oligosaccharide sulfation pattern on the stimulation of acidic fibroblast growth factor (FGF-1) induced mitogenesis signaling and the biological significance of FGF-1 trans dimerization in the FGF-1 activation process. It has been found that some molecules with a sulfation pattern that does not contain the internal trisaccharide motif, which has been proposed for high affinity for FGF-1, stimulate FGF-1 more efficiently than those with the structure of the regular region of heparin. In contrast to regular region oligosaccharides, in which the sulfate groups are distributed on both sides of their helical three-dimensional structures, the molecules containing this particular sulfation pattern display the sulfate groups only on one side of the helix. These results and the fact that these oligosaccharides do not promote FGF-1 dimerization according to sedimentation-equilibrium analysis, confirm the importance of negative-charge distribution in the activation process and strongly suggest that FGF dimerization is not a general and absolute requirement for biological activity.

Advances in the Study of the Structures and Bioactivities of Metabolites Isolated from Mangrove-Derived Fungi in the South China Sea

PubMed Central

Wang, Xin; Mao, Zhi-Gang; Song, Bing-Bing; Chen, Chun-Hua; Xiao, Wei-Wei; Hu, Bin; Wang, Ji-Wen; Jiang, Xiao-Bing; Zhu, Yong-Hong; Wang, Hai-Jun

2013-01-01

Many metabolites with novel structures and biological activities have been isolated from the mangrove fungi in the South China Sea, such as anthracenediones, xyloketals, sesquiterpenoids, chromones, lactones, coumarins and isocoumarin derivatives, xanthones, and peroxides. Some compounds have anticancer, antibacterial, antifungal and antiviral properties, but the biosynthesis of these compounds is still limited. This review summarizes the advances in the study of secondary metabolites from the mangrove-derived fungi in the South China Sea, and their biological activities reported between 2008 and mid-2013. PMID:24084782

Design and preliminary structure-activity relationship of redox-silent semisynthetic tocotrienol analogues as inhibitors for breast cancer proliferation and invasion.

PubMed

Elnagar, Ahmed Y; Wali, Vikram B; Sylvester, Paul W; El Sayed, Khalid A

2010-01-15

Vitamin E (VE) is a generic term that represents a family of compounds composed of various tocopherol and tocotrienol isoforms. Tocotrienols display potent anti-angiogenic and antiproliferative activities. Redox-silent tocotrienol analogues also display potent anticancer activity. The ultimate objective of this study was to develop semisynthetically C-6-modified redox-silent tocotrienol analogues with enhanced antiproliferative and anti-invasive activities as compared to their parent compound. Examples of these are carbamate and ether analogues of alpha-, gamma-, and delta-tocotrienols (1-3). Various aliphatic, olefinic, and aromatic substituents were used. Steric limitation, electrostatic, hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) properties were varied at this position and the biological activities of these derivatives were tested. Three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed using Comparative Molecular Field (CoMFA) and Comparative Molecular Similarity Indices Analyses (CoMSIA) to better understand the structural basis for biological activity and guide the future design of more potent VE analogues. Copyright 2009 Elsevier Ltd. All rights reserved.

New Bioactive Compounds from Korean Native Mushrooms

PubMed Central

Kim, Seong-Eun; Hwang, Byung Soon; Song, Ja-Gyeong; Lee, Seung Woong; Lee, In-Kyoung

2013-01-01

Mushrooms are ubiquitous in nature and have high nutritional attributes. They have demonstrated diverse biological effects and therefore have been used in treatments of various diseases, including cancer, diabetes, bacterial and viral infections, and ulcer. In particular, polysaccharides, including β-glucan, are considered as the major constituents responsible for the biological activity of mushrooms. Although an overwhelming number of reports have been published on the importance of polysaccharides as immunomodulating agents, not all of the healing properties found in these mushrooms could be fully accounted for. Recently, many research groups have begun investigations on biologically active small-molecular weight compounds in wild mushrooms. In this mini-review, both structural diversity and biological activities of novel bioactive substances from Korean native mushrooms are described. PMID:24493936

Papulacandins, a new family of antibiotics with antifungal activity, I. Fermentation, isolation, chemical and biological characterization of papulacandins A, B, C, D and E.

PubMed

Traxler, P; Gruner, J; Auden, J A

1977-04-01

Papulacandin, a new antibiotic complex, active against Candida albicans and several other yeasts, was isolated from a strain of Papularia sphaerosperma. The fermentation, isolation, physico-chemical properties and biological activity of the five structurally related papulacandins A, B, C, D and E are reported. Papulacandin B, the main component, was assigned the formula of C47H64O17.

C-terminal Lysine-Linked Magainin 2 with Increased Activity Against Multidrug-Resistant Bacteria.

PubMed

Lorenzón, Esteban N; Santos-Filho, Norival A; Ramos, Matheus A S; Bauab, Tais M; Camargo, Ilana L B C; Cilli, Eduardo M

2016-01-01

Due to the growing problem of antibiotic-resistant microorganisms, the development of novel antimicrobial agents is a very important challenge. Dimerization of cationic antimicrobial peptides (cAMPs) is a potential strategy for enhancing antimicrobial activity. Here, we studied the effects of magainin 2 (MG2) dimerization on its structure and biological activity. Lysine and glutamic acid were used to synthesize the C- and N-terminal dimers of MG2, respectively, in order to evaluate the impact of linker position used to obtain the dimers. Both MG2 and its dimeric versions showed a random coil structure in aqueous solution. However, in the presence of a structure-inducing solvent or a membrane mimetic, all peptides acquired helical structure. N-terminal dimerization did not affect the biological activity of the peptide. On the other hand, the C-terminal dimer, (MG2)2K, showed antimicrobial activity 8-16 times higher than that of MG2, and the time required to kill Escherichia coli was lower. The enhanced antimicrobial activity was related to membrane permeabilization. (MG2)2K was also more active against multidrug-resistant bacteria of clinical origin. Overall, the results presented here demonstrate that C-terminal lysine-linked dimerization improve the activity of MG2, and (MG2)2K can be considered as a potential antimicrobial agent.

Synthesis, structural characterization and biological activity of two diastereomeric JA-Ile macrolactones.

PubMed

Jimenez-Aleman, Guillermo H; Machado, Ricardo A R; Görls, Helmar; Baldwin, Ian T; Boland, Wilhelm

2015-06-07

Jasmonates are phytohormones involved in a wide range of plant processes, including growth, development, senescence, and defense. Jasmonoyl-L-isoleucine (JA-Ile, 2), an amino acid conjugate of jasmonic acid (JA, 1), has been identified as a bioactive endogenous jasmonate. However, JA-Ile (2) analogues trigger different responses in the plant. ω-Hydroxylation of the pentenyl side chain leads to the inactive 12-OH-JA-Ile (3) acting as a “stop” signal. On the other hand, a lactone derivative of 12-OH-JA (5) (jasmine ketolactone, JKL) occurs in nature, although with no known biological function. Inspired by the chemical structure of JKL (6) and in order to further explore the potential biological activities of 12-modified JA-Ile derivatives, we synthesized two macrolactones (JA-Ile-lactones (4a) and (4b)) derived from 12-OH-JA-Ile (3). The biological activity of (4a) and (4b) was tested for their ability to elicit nicotine production, a well-known jasmonate dependent secondary metabolite. Both macrolactones showed strong biological activity, inducing nicotine accumulation to a similar extent as methyl jasmonate does in Nicotiana attenuata leaves. Surprisingly, the highest nicotine contents were found in plants treated with the JA-Ile-lactone (4b), which has (3S,7S) configuration at the cyclopentanone not known from natural jasmonates. Macrolactone (4a) is a valuable standard to explore for its occurrence in nature.

The synthesis and biological activity of 4-[bis(2-chloroethyl)amino]-DL-, L, and D-phenylalanine amides and peptides

NASA Astrophysics Data System (ADS)

Krasnov, Victor P.; Zhdanova, E. A.; Smirnova, L. I.

1995-11-01

The review is devoted to the synthesis and biological properties of the amides and peptides containing the stereoisomers of 4-[bis(2-chloroethyl)amino]phenylalanine. The approaches to the selection of the structures of the compounds indicated, ensuring an increase in the selectivity of their antitumour activity, are examined. The bibliography includes 131 references.

Polysaccharides from the South African medicinal plant Artemisia afra: Structure and activity studies.

PubMed

Braünlich, Paula Marie; Inngjerdingen, Kari Tvete; Inngjerdingen, Marit; Johnson, Quinton; Paulsen, Berit Smestad; Mabusela, Wilfred

2018-01-01

Artemisia afra (Jacq. Ex. Willd), is an indigenous plant in South Africa and other parts of the African continent, where it is used as traditional medicine mostly for respiratory conditions. The objective of this study was to investigate the structural features of the polysaccharides from the leaves of this plant, as well as the biological activities of the polysaccharide fractions against the complement assay. Leaves of Artemisia afra were extracted sequentially with organic solvents (dichloromethane and methanol), 50% aqueous ethanol, and water at 50 and 100°C respectively. The polysaccharide extracts were fractionated by ion exchange chromatography and the resulting fractions were tested for biological activity against the complement fixation assay. Active fractions were further fractionated using gel filtration. Monosaccharide compositions and linkage analyses were determined for the relevant fractions. Polysaccharides were shown to be of the pectin type, and largely contain arabinogalactan, rhamnogalacturonan and homogalacturonan structural features. The presence of arabinogalactan type II features as suggested by methylation analysis was further confirmed by the ready precipitation of the relevant polysaccharides with the Yariv reagent. An unusual feature of some of these polysaccharides was the presence of relatively high levels of xylose as one of its monosaccharide constituents. Purified polysaccharide fractions were shown to possess higher biological activity than the selected standard in the complement assay. Digestion of these polysaccharides with an endo-polygalacturonase enzyme resulted in polymers with lower molecular weights as expected, but still with biological activity which exceeded that of the standard. Thus on the basis of these studies it may be suggested that immunomodulating properties probably contribute significantly to the health-promoting effects of this medicinal plant. Copyright © 2017 Elsevier B.V. All rights reserved.

Structures and properties of naturally occurring polyether antibiotics.

PubMed

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties.

Structures and Properties of Naturally Occurring Polyether Antibiotics

PubMed Central

Rutkowski, Jacek; Brzezinski, Bogumil

2013-01-01

Polyether ionophores represent a large group of natural, biologically active substances produced by Streptomyces spp. They are lipid soluble and able to transport metal cations across cell membranes. Several of polyether ionophores are widely used as growth promoters in veterinary. Polyether antibiotics show a broad spectrum of bioactivity ranging from antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Recently, it has been shown that some of these compounds are able to selectively kill cancer stem cells and multidrug-resistant cancer cells. Thus, they are recognized as new potential anticancer drugs. The biological activity of polyether ionophores is strictly connected with their molecular structure; therefore, the purpose of this paper is to present an overview of their formula, molecular structure, and properties. PMID:23586016

Molecular mechanism of biological and therapeutical effect of low-intensity laser irradiation

NASA Astrophysics Data System (ADS)

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Plavskaja, Ljudmila G.; Morozova, Raisa P.

1995-05-01

The investigations carried out in our group on biological systems of various organization level (enzyme molecules in solution, human and animal cell cultures), allowed us to conclude, that the light-induced changes of spatial structure of cells components form the basis of biological activity (and as a consequence therapeutic effect) of various wavelength low-intensity laser emission. Photophysical mechanism of these changes lies in the reorientation of highregulated anisotropic parts (domains) with the liquid-crystalline type of ordering of the cell components due to the interaction between the electric field and the light induced integral electric dipole of the domain. The mechanism of such reorientation is well established in physics of liquid crystals of nematic type and is known as light induced analogue of Frederix's effect. The following results enable us to draw the conclusion about the determining role of the orientations effects on the biological activity mechanism of low-intensity laser radiation: (i) the possibility of reversible modification of spatial structure and enzyme molecules functional activity under the influence of laser radiation outside the band of their own or admixture absorption; (ii) the dependence of biological effect of laser radiation on the functional activity of cells vs. polarization degree of the light with the maximum photobiological effects observed for linear-polarized radiation; (iii) the equivalence of a static magnetic field and low-intensity laser radiation in action on functional activity of the cells and the lowering of the laser field intensity for the achieving the difinite changes of the cell functional activity in the presence of static magnetic field.

Application of Time-Resolved Tryptophan Phosphorescence Spectroscopy to Protein Folding Studies.

NASA Astrophysics Data System (ADS)

Subramaniam, Vinod

This thesis presents studies of the protein folding problem, one of the most significant questions in contemporary biophysics. Sensitive biophysical techniques, including room temperature tryptophan phosphorescence, which reports on the local environment of the residue, and the lability of proteins to denaturation, a global parameter, were used to assess the validity of the traditional assumption that the biologically active state of a protein is the 'native' state, and to determine whether the pathways of folding in vitro lead to the folded state achieved in vivo. Phosphorescence techniques have also been extended to study, for the first time, emission from tryptophan residues engineered into specific positions as reporters of protein structure. During in vitro refolding of E. coli alkaline phosphatase and bovine 13-lactoglobulin, significant differences were found between the refolded proteins and the native conformations, which have no apparent effect on the biological functions. Slow conformational transitions, termed 'annealing,' that occur long after the return of enzyme activity of alkaline phosphatase are manifested in the retarded recovery of phosphorescence intensity, lifetime, and protein lability. While 'annealing' is not observed for beta -lactoglobulin, both phosphorescence and lability experiments reveal changes in the structure of the refolded protein, even though its biological activity, retinol binding, is fully recovered. This result suggests that the pathways of folding in vitro need not lead to the structure formed in vivo. We have used phosphorescence techniques to study the refolding of ribonuclease T1, which exhibits slow kinetics characteristic of proline isomerization. Furthermore, the ability to extract structural information from phosphorescent tryptophan probes engineered into selected regions represents an important advance in studying protein structure; we have reported the first such results from a mutant staphylococcal nuclease. The refolding data have been interpreted in the context of recent theoretical work on rugged energy landscape models of protein folding. Our results suggest that the barriers to folding can be as large as ~ 20 kcal-mol^{-1}, and imply that the conventional definition of the 'native' state as the biologically active conformation may need revision to acknowledge that the active state may represent a long-lived intermediate on the pathway to the native structure.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON ...

EPA Pesticide Factsheets

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives that are accelerating the pace of this transformation, with particular reference to toxicology-related chemical information. Chemical content annotators, structure locator services, large structure/data aggregator web sites, structure browsers, International Union of Pure and Applied Chemistry (IUPAC) International Chemical Identifier (InChI) codes, toxicity data models and public chemical/biological activity profiling initiatives are all playing a role in overcoming barriers to the integration of toxicity data, and are bringing researchers closer to the reality of a mineable chemical Semantic Web. An example of this integration of data is provided by the collaboration among researchers involved with the Distributed Structure-Searchable Toxicity (DSSTox) project, the Carcinogenic Potency Project, projects at the National Cancer Institute and the PubChem database. Standardizing chemical structure annotation of public toxicity databases

Insight into the structural requirements of aminopyrimidine derivatives for good potency against both purified enzyme and whole cells of M. tuberculosis: combination of HQSAR, CoMSIA, and MD simulation studies.

PubMed

Punkvang, Auradee; Hannongbua, Supa; Saparpakorn, Patchreenart; Pungpo, Pornpan

2016-05-01

The Mycobacterium tuberculosis protein kinase B (PknB) is critical for growth and survival of M. tuberculosis within the host. The series of aminopyrimidine derivatives show impressive activity against PknB (IC50 < .5 μM). However, most of them show weak or no cellular activity against M. tuberculosis (MIC > 63 μM). Consequently, the key structural features related to activity against of both PknB and M. tuberculosis need to be investigated. Here, two- and three-dimensional quantitative structure-activity relationship (2D and 3D QSAR) analyses combined with molecular dynamics (MD) simulations were employed with the aim to evaluate these key structural features of aminopyrimidine derivatives. Hologram quantitative structure-activity relationship (HQSAR) and CoMSIA models constructed from IC50 and MIC values of aminopyrimidine compounds could establish the structural requirements for better activity against of both PknB and M. tuberculosis. The NH linker and the R1 substituent of the template compound are not only crucial for the biological activity against PknB but also for the biological activity against M. tuberculosis. Moreover, the results obtained from MD simulations show that these moieties are the key fragments for binding of aminopyrimidine compounds in PknB. The combination of QSAR analysis and MD simulations helps us to provide a structural concept that could guide future design of PknB inhibitors with improved potency against both the purified enzyme and whole M. tuberculosis cells.

Total Synthesis and Structure-Activity Investigation of the Marine Natural Product Neopeltolide

PubMed Central

Custar, Daniel W.; Zabawa, Thomas P.; Hines, John; Crews, Craig M.; Scheidt, Karl A.

2009-01-01

The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity. PMID:19663512

Raman Optical Activity of Biological Molecules

NASA Astrophysics Data System (ADS)

Blanch, Ewan W.; Barron, Laurence D.

Now an incisive probe of biomolecular structure, Raman optical activity (ROA) measures a small difference in Raman scattering from chiral molecules in right- and left-circularly polarized light. As ROA spectra measure vibrational optical activity, they contain highly informative band structures sensitive to the secondary and tertiary structures of proteins, nucleic acids, viruses and carbohydrates as well as the absolute configurations of small molecules. In this review we present a survey of recent studies on biomolecular structure and dynamics using ROA and also a discussion of future applications of this powerful new technique in biomedical research.

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology

PubMed Central

Galdeano, Carles; Ciulli, Alessio

2017-01-01

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity. PMID:27193077

Design of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes: A History Driven by Biology to Chemistry.

PubMed

Cai, Wenqing; Jiang, Linlin; Xie, Yafei; Liu, Yuqiang; Liu, Wei; Zhao, Guilong

2015-01-01

A brief history of the design of sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors is reviewed. The design of O-glucoside SGLT2 inhibitors by structural modification of phlorizin, a naturally occurring O-glucoside, in the early stage was a process mainly driven by biology with anticipation of improving SGLT2/SGLT1 selectivity and increasing metabolic stability. Discovery of dapagliflozin, a pioneering C-glucoside SGLT2 inhibitor developed by Bristol-Myers Squibb, represents an important milestone in this history. In the second stage, the design of C-glycoside SGLT2 inhibitors by modifications of the aglycone and glucose moiety of dapagliflozin, an original structural template for almost all C-glycoside SGLT2 inhibitors, was mainly driven by synthetic organic chemistry due to the challenge of designing dapagliflozin derivatives that are patentable, biologically active and synthetically accessible. Structure-activity relationships (SAR) of the SGLT2 inhibitors are also discussed.

Synthesis and biological activities of turkesterone 11α-acyl derivatives

PubMed Central

Dinan, Laurence; Bourne, Pauline; Whiting, Pensri; Tsitsekli, Ada; Saatov, Ziyadilla; Dhadialla, Tarlochan S.; Hormann, Robert E.; Lafont, René; Coll, Josep

2003-01-01

Turkesterone is a phytoecdysteroid possessing an 11α-hydroxyl group. It is an analogue of the insect steroid hormone 20-hydroxyecdysone. Previous ecdysteroid QSAR and molecular modelling studies predicted that the cavity of the ligand binding domain of the ecdysteroid receptor would possess space in the vicinity of C-11/C-12 of the ecdysteroid. We report the regioselective synthesis of a series of turkesterone 11α-acyl derivatives in order to explore this possibility. The structures of the analogues have been unambiguously determined by spectroscopic means (NMR and low-resolution mass spectrometry). Purity was verified by HPLC. Biological activities have been determined in Drosophila melanogaster BII cell-based bioassay for ecdysteroid agonists and in an in vitro radioligand-displacement assay using bacterially-expressed D. melanogaster EcR/USP receptor proteins. The 11α-acyl derivatives do retain a significant amount of biological activity relative to the parent ecdysteroid. Further, although activity initially drops with the extension of the acyl chain length (C2 to C4), it then increases (C6 to C10), before decreasing again (C14 and C20). The implications of these findings for the interaction of ecdysteroids with the ecdysteroid receptor and potential applications in the generation of affinity-labelled and fluorescently-tagged ecdysteroids are discussed. Abbreviation: CoMFA comparative molecular field analysis DCM dichloromethane DMF dimethylformamide DMP 2,2-dimethoxypropane 4D-QSAR 4-dimensional quantitative structure-activity relationship EcR ecdysteroid receptor EcRE ecdysteroid response element HPLC high-performance liquid chromatography LBD ligand-binding domain NMR nuclear magnetic resonance ponA ponasterone A QSAR quantitative structure-activity relationship RXR retinoid X receptor SAR structure-activity relationship SPE solid-phase extraction THF tetrahydrofuran TLC thin-layer chromatography p-TsOH para-toluenesulphonic acid USP ultraspiracle UV-VIS ultraviolet-visible PMID:15841223

Statistical molecular design of balanced compound libraries for QSAR modeling.

PubMed

Linusson, A; Elofsson, M; Andersson, I E; Dahlgren, M K

2010-01-01

A fundamental step in preclinical drug development is the computation of quantitative structure-activity relationship (QSAR) models, i.e. models that link chemical features of compounds with activities towards a target macromolecule associated with the initiation or progression of a disease. QSAR models are computed by combining information on the physicochemical and structural features of a library of congeneric compounds, typically assembled from two or more building blocks, and biological data from one or more in vitro assays. Since the models provide information on features affecting the compounds' biological activity they can be used as guides for further optimization. However, in order for a QSAR model to be relevant to the targeted disease, and drug development in general, the compound library used must contain molecules with balanced variation of the features spanning the chemical space believed to be important for interaction with the biological target. In addition, the assays used must be robust and deliver high quality data that are directly related to the function of the biological target and the associated disease state. In this review, we discuss and exemplify the concept of statistical molecular design (SMD) in the selection of building blocks and final synthetic targets (i.e. compounds to synthesize) to generate information-rich, balanced libraries for biological testing and computation of QSAR models.

Lysine acetyltransferase inhibitors: structure-activity relationships and potential therapeutic implications.

PubMed

Fiorentino, Francesco; Mai, Antonello; Rotili, Dante

2018-05-01

Lysine acetylation is a post-translational modification of both histone and nonhistone proteins that is catalyzed by lysine acetyltransferases and plays a key role in numerous biological contexts. The dysregulation of this enzyme activity is implicated in many human pathologies such as cancer, neurological and inflammatory disorders. Many lysine acetyltransferase inhibitors (KATi) have been developed so far, but there is still the need for new, more potent, metabolically stable and selective KATi as chemical tools for studying KAT biology and/or as potential therapeutic agents. This review will examine the features of KAT enzymes and related diseases, with particular emphasis on KATi (bisubstrate analogs, natural compounds and synthetic derivatives), analyzing their mechanism of action, structure-activity relationships, pharmacokinetic/pharmacodynamic properties and potential future applications.

Synthesis and biological evaluation of Raddeanin A, a triterpene saponin isolated from Anemone raddeana.

PubMed

Qian, Shan; Chen, Quan Long; Guan, Jin Long; Wu, Yong; Wang, Zhou Yu

2014-01-01

First, Raddeanin A, a cytotoxic oleanane-type triterpenoid saponin isolated from Anemone raddeana REGEL, was synthesized. Stepwise glycosylation was adopted in the synthesis from oleanolic acid, employing arabinosyl, glucosyl and rhamnosyl trichloroacetimidate as donors. The chemical structure of Raddeanin A was confirmed by means of (1)H-NMR, (13)C-NMR, IR, MS and elemental analysis, which elucidated the structure to be 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranoside oleanolic acid. Biological activity tests showed that in the range of low concentrations, Raddeanin A displayed moderate inhibitory activity against histone deacetylases (HDACs), indicating that the HDACs' inhibitory activity of Raddeanin A may contribute to its cytotoxicity.

Total synthesis and biological activity of the proposed structure of phaeosphaeride A.

PubMed

Chatzimpaloglou, Anthoula; Yavropoulou, Maria P; Rooij, Karien E; Biedermann, Ralf; Mueller, Uwe; Kaskel, Stefan; Sarli, Vasiliki

2012-11-02

The total synthesis of the structure assigned to the natural product phaeosphaeride A 1a was accomplished. The key steps involve the addition of vinyllithium reagent 7 to the acetonide-protected aldehyde 8 to access the carbon backbone of 1a, the introduction of the methoxylamino group followed by intramolecular hetero-Michael cyclization, and methanol elimination to form the dihydropyran ring. In this study, both enantiomers of 1a were synthesized and tested for biological activity. Preliminary results showed that (6R,7R,8R)-1a and (6S,7S,8S)-1a inhibit STAT3-dependent transcriptional activity in a dose-dependent manner and exhibit antiproliferative properties in breast (MDA-MB-231) and pancreatic (PANC-1) cancer cells.

The Androgen Receptor and Its Use in Biological Assays: Looking Toward Effect-Based Testing and Its Applications

PubMed Central

Cadwallader, Amy B.; Lim, Carol S.; Rollins, Douglas E.; Botrè, Francesco

2015-01-01

Steroid abuse is a growing problem among amateur and professional athletes. Because of an inundation of newly and illegally synthesized steroids with minor structural modifications and other designer steroid receptor modulators, there is a need to develop new methods of detection which do not require prior knowledge of the abused steroid structure. The number of designer steroids currently being abused is unknown because detection methods in general are only identifying substances with a known structure. The detection of doping is moving away from merely checking for exposure to prohibited substance toward detecting an effect of prohibited substances, as biological assays can do. Cell-based biological assays are the next generation of assays which should be utilized by antidoping laboratories; they can detect androgenic anabolic steroid and other human androgen receptor (hAR) ligand presence without knowledge of their structure and assess the relative biological activity of these compounds. This review summarizes the hAR and its action and discusses its relevance to sports doping and its use in biological assays. PMID:22080898

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation.

PubMed

Zayed, Ehab M; Zayed, M A

2015-05-15

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N',N'″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2'-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and (1)H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE(∗), ΔH(∗), ΔS(∗) and ΔG(∗) were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis of novel Schiff's bases of highly potential biological activities and their structure investigation

NASA Astrophysics Data System (ADS)

Zayed, Ehab M.; Zayed, M. A.

2015-05-01

Novel bisaldehyde-hydrazide Schiff's bases AS1 (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde terephthalohydrazide) and AS2 (N‧,N‧″-(((ethane-1,2-diylbis(oxy))bis(2,1-phenylene))bis(methanylylidene))di(benzohydrazide)) were prepared as new macrocyclic compounds via condensation reactions. AS1 had been prepared by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and terephthalohydrazide in a ratio1:1. AS2 had been obtained by condensation between (2,2‧-(ethane-1,2-diylbis(oxy))dibenzaldehyde) bisaldehyde and benzohydrazide in ratio 1:2. The structures of AS1 and AS2 were characterized by elemental analysis (EA), mass (MS), FT-IR and 1H-NMR spectra, and thermal analyses (TG, DTG). The activation thermodynamic parameters such as ΔE∗, ΔH∗, ΔS∗ and ΔG∗ were calculated from the TG curves using Coats-Redfern method. It is important to investigate their molecular structures to know the active groups and weak bonds responsible for their biological activities. Consequently in the present work, the obtained thermal (TA) and mass (MS) practical results are confirmed by semi-empirical MO-calculations (MOCS) using PM3 procedure. Their biological activities had been tested in vitro against Escherichia coli, Proteus vulgaris, Bacillus subtilis and Staphylococcus aurous bacteria in order to assess their anti-microbial potential.

Auto-induction for high level production of biologically active reteplase in Escherichia coli.

PubMed

Fathi-Roudsari, Mehrnoosh; Maghsoudi, Nader; Maghsoudi, Amirhossein; Niazi, Sepideh; Soleiman, Morvarid

2018-06-07

Reteplase is a third generation tissue plasminogen activator (tPA) with a modified structure and prolonged half-life in comparison to native tPA. As a non-glycosylated protein, reteplase is expressed in Escherichia coli. Due to presence of several disulfide bonds, high level production of reteplase is complicated and needs extra steps for conversion to biologically active form. Auto-induction represents a method for high-yield growth of bacterial cells and higher expression of recombinant proteins. Here we have tried to optimize the auto-induction procedure for soluble and active expression of reteplase in E. coli. Results showed that using auto-induction strategy at 37 °C, Rosetta-gami (DE3) had the highest level of active and soluble reteplase production in comparison to E. coli strains BL21 (DE3), and Shuffel T7. Temperature dominantly affected the level of active reteplase production. Decreasing the temperature to 25 and 18 °C increased the level of active reteplase by 20 and 60%, respectively. The composition of auto-induction medium also dramatically changed the active production of reteplase in cytoplasm. Using higher enriched auto-induction medium, super broth base including trace elements, significantly increased biologically active reteplase by 30%. It is demonstrated here that auto-induction is a powerful method for expression of biologically active reteplase in oxidative cytoplasm of Rosetta-gami. Optimizing expression condition by decreasing temperature and using an enriched auto-induction medium resulted in at least three times higher level of active reteplase production. Production of correctly folded and active reteplase in spite of its complex structure helps for removal of inefficient and cumbersome step of refolding. Copyright © 2018. Published by Elsevier Inc.

Structure and Chemical Synthesis of a Biologically Active Form of Renilla (Sea Pansy) Luciferin*

PubMed Central

Hori, Kazuo; Cormier, Milton J.

1973-01-01

The structure of a biologically active form of Renilla (sea pansy) luciferin has been elucidated; this structure, confirmed by total chemical synthesis, is 3,7-dihydro-2-methyl-6-(p-hydroxyphenyl)-8-benzylimidazo [1,2-a] pyrazin-3-one. In the natural compound the methyl group at the 2 position is replaced by an unknown, more complex group. For this reason the synthetic compound is 10% as active as the natural compound in producing light with Renilla luciferase. However, the spectral properties of the two compounds are identical. In addition the rates of the luminescent reaction with both compounds are similar, and the color of the light produced is identical in each case. A compound isolated from the calcium-triggered photoprotein aequorin has been identified by Shimomura and Johnson [(1972) Biochemistry 11, 1602] to be 2-amino-3-benzyl-5-(p-hydroxyphenyl)pyrazine. This compound forms an integral part of the structure of Renilla luciferin. This, and other evidence, suggests that the structure elucidated for Renilla luciferin is a more general one associated with the luciferins of most, if not all, bioluminescent coelenterates. PMID:16592045

The application of the multi-alternative approach in active neural network models

NASA Astrophysics Data System (ADS)

Podvalny, S.; Vasiljev, E.

2017-02-01

The article refers to the construction of intelligent systems based artificial neuron networks are used. We discuss the basic properties of the non-compliance of artificial neuron networks and their biological prototypes. It is shown here that the main reason for these discrepancies is the structural immutability of the neuron network models in the learning process, that is, their passivity. Based on the modern understanding of the biological nervous system as a structured ensemble of nerve cells, it is proposed to abandon the attempts to simulate its work at the level of the elementary neurons functioning processes and proceed to the reproduction of the information structure of data storage and processing on the basis of the general enough evolutionary principles of multialternativity, i.e. the multi-level structural model, diversity and modularity. The implementation method of these principles is offered, using the faceted memory organization in the neuron network with the rearranging active structure. An example of the implementation of the active facet-type neuron network in the intellectual decision-making system in the conditions of critical events development in the electrical distribution system.

Marine Antifreeze Proteins: Structure, Function, and Application to Cryopreservation as a Potential Cryoprotectant

PubMed Central

Kim, Hak Jun; Lee, Jun Hyuck; Hur, Young Baek; Lee, Chang Woo; Park, Sun-Ha; Koo, Bon-Won

2017-01-01

Antifreeze proteins (AFPs) are biological antifreezes with unique properties, including thermal hysteresis (TH), ice recrystallization inhibition (IRI), and interaction with membranes and/or membrane proteins. These properties have been utilized in the preservation of biological samples at low temperatures. Here, we review the structure and function of marine-derived AFPs, including moderately active fish AFPs and hyperactive polar AFPs. We also survey previous and current reports of cryopreservation using AFPs. Cryopreserved biological samples are relatively diverse ranging from diatoms and reproductive cells to embryos and organs. Cryopreserved biological samples mainly originate from mammals. Most cryopreservation trials using marine-derived AFPs have demonstrated that addition of AFPs can improve post-thaw viability regardless of freezing method (slow-freezing or vitrification), storage temperature, and types of biological sample type. PMID:28134801

Synthesis and molecular docking of some novel anticancer sulfonamides carrying a biologically active pyrrole and pyrrolopyrimidine moieties.

PubMed

Ghorab, Mostafa M; Alsaid, Mansour S; Nissan, Yassin M

2014-01-01

Abstract: A novel series of pyrroles and pyrrolopyrimdines carrying a biologically active sulfonamide moiety have been synthesized. The structures were confirmed by elemental analyses and spectral data. All the target compounds were subjected to in vitro cytotoxic screening on breast cancer cell line (MCF-7). Most of the synthesized compounds showed good activity as cytotoxic agents with better IC50 than doxorubicin as a reference drug. In order to suggest a mechanism of action for their activity, molecular docking on the active site of human c-Src was performed for all synthesized compounds.

Overview on Biological Activities and Molecular Characteristics of Sulfated Polysaccharides from Marine Green Algae in Recent Years

PubMed Central

Wang, Lingchong; Wang, Xiangyu; Wu, Hao; Liu, Rui

2014-01-01

Among the three main divisions of marine macroalgae (Chlorophyta, Phaeophyta and Rhodophyta), marine green algae are valuable sources of structurally diverse bioactive compounds and remain largely unexploited in nutraceutical and pharmaceutical areas. Recently, a great deal of interest has been developed to isolate novel sulfated polysaccharides (SPs) from marine green algae because of their numerous health beneficial effects. Green seaweeds are known to synthesize large quantities of SPs and are well established sources of these particularly interesting molecules such as ulvans from Ulva and Enteromorpha, sulfated rhamnans from Monostroma, sulfated arabinogalactans from Codium, sulfated galacotans from Caulerpa, and some special sulfated mannans from different species. These SPs exhibit many beneficial biological activities such as anticoagulant, antiviral, antioxidative, antitumor, immunomodulating, antihyperlipidemic and antihepatotoxic activities. Therefore, marine algae derived SPs have great potential for further development as healthy food and medical products. The present review focuses on SPs derived from marine green algae and presents an overview of the recent progress of determinations of their structural types and biological activities, especially their potential health benefits. PMID:25257786

Fishy Activities for Your Small Fry. A Unit Plan in Fish Biology for Grades Kindergarten through Sixth. Educational Series Number 28.

ERIC Educational Resources Information Center

Sparrow, Mary E.; And Others

This unit in fish biology is suitable for kindergarten through sixth grade. Provided in the unit are: (1) behavioral objectives for grades K-3 and 4-6; (2) an overview of activities and instructional strategies; (3) background information on fishes; (4) diagrams of internal/external fish structure; (5) list of key vocabulary words; (6) discussion…

Biology Division progress report, October 1, 1991--September 30, 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hartman, F.C.; Cook, J.S.

This Progress Report summarizes the research endeavors of the Biology Division of the Oak Ridge National Laboratory during the period October 1, 1991, through September 30, 1993. The report is structured to provide descriptions of current activities and accomplishments in each of the Division`s major organizational units. Lists of information to convey the entire scope of the Division`s activities are compiled at the end of the report.

Novel coumarins and related copper complexes with biological activity: DNA binding, molecular docking and in vitro antiproliferative activity.

PubMed

Pivetta, Tiziana; Valletta, Elisa; Ferino, Giulio; Isaia, Francesco; Pani, Alessandra; Vascellari, Sarah; Castellano, Carlo; Demartin, Francesco; Cabiddu, Maria Grazia; Cadoni, Enzo

2017-12-01

Coumarins show biological activity and are widely exploited for their therapeutic effects. Although a great number of coumarins substituted by heterocyclic moieties have been prepared, few studies have been carried out on coumarins containing pyridine heterocycle, which is known to modulate their physiological activities. We prepared and characterized three novel 3-(pyridin-2-yl)coumarins and their corresponding copper(II) complexes. We extended our investigations also to three known similar coumarins, since no data about their biochemical activity was previously been reported. The antiproliferative activity of the studied compounds was tested against human derived tumor cell lines and one human normal cell line. The DNA binding constants were determined and docking studies with DNA carried out. Selected Quantitative Structure-Activity Relationship (QSAR) descriptors were calculated in order to relate a set of structural and topological descriptors of the studied compounds to their DNA interaction and cytotoxic activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

NASA Astrophysics Data System (ADS)

Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

2013-06-01

Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

Recent Advances in the Chemistry and Biology of Podophyllotoxins.

PubMed

Yu, Xiang; Che, Zhiping; Xu, Hui

2017-04-03

Podophyllotoxin and its related aryltetralin cyclolignans belong to a family of important products that exhibit various biological properties (e.g., cytotoxic, insecticidal, antifungal, antiviral, anti-inflammatory, neurotoxic, immunosuppressive, antirheumatic, antioxidative, antispasmogenic, and hypolipidemic activities). This Review provides a survey of podophyllotoxin and its analogues isolated from plants. In particular, recent developments in the elegant total chemical synthesis, structural modifications, biosynthesis, and biotransformation of podophyllotoxin and its analogues are summarized. Moreover, a deoxypodophyllotoxin-based chemosensor for selective detection of mercury ion is described. In addition to the most active podophyllotoxin derivatives in each series against human cancer cell lines and insect pests listed in the tables, the structure-activity relationships of podophyllotoxin derivatives as cytotoxic and insecticidal agents are also outlined. Future prospects and further developments in this area are covered at the end of the Review. We believe that this Review will provide necessary information for synthetic, medicinal, and pesticidal chemistry researchers who are interested in the chemistry and biology of podophyllotoxins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A structured viroid RNA serves as a substrate for dicer-like cleavage to produce biologically active small RNAs but is resistant to RNA-induced silencing complex-mediated degradation.

PubMed

Itaya, Asuka; Zhong, Xuehua; Bundschuh, Ralf; Qi, Yijun; Wang, Ying; Takeda, Ryuta; Harris, Ann R; Molina, Carlos; Nelson, Richard S; Ding, Biao

2007-03-01

RNA silencing is a potent means of antiviral defense in plants and animals. A hallmark of this defense response is the production of 21- to 24-nucleotide viral small RNAs via mechanisms that remain to be fully understood. Many viruses encode suppressors of RNA silencing, and some viral RNAs function directly as silencing suppressors as counterdefense. The occurrence of viroid-specific small RNAs in infected plants suggests that viroids can trigger RNA silencing in a host, raising the question of how these noncoding and unencapsidated RNAs survive cellular RNA-silencing systems. We address this question by characterizing the production of small RNAs of Potato spindle tuber viroid (srPSTVds) and investigating how PSTVd responds to RNA silencing. Our molecular and biochemical studies provide evidence that srPSTVds were derived mostly from the secondary structure of viroid RNAs. Replication of PSTVd was resistant to RNA silencing, although the srPSTVds were biologically active in guiding RNA-induced silencing complex (RISC)-mediated cleavage, as shown with a sensor system. Further analyses showed that without possessing or triggering silencing suppressor activities, the PSTVd secondary structure played a critical role in resistance to RISC-mediated cleavage. These findings support the hypothesis that some infectious RNAs may have evolved specific secondary structures as an effective means to evade RNA silencing in addition to encoding silencing suppressor activities. Our results should have important implications in further studies on RNA-based mechanisms of host-pathogen interactions and the biological constraints that shape the evolution of infectious RNA structures.

Super-resolution binding activated localization microscopy through reversible change of DNA conformation.

PubMed

Szczurek, Aleksander; Birk, Udo; Knecht, Hans; Dobrucki, Jurek; Mai, Sabine; Cremer, Christoph

2018-01-01

Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine.

Super-resolution binding activated localization microscopy through reversible change of DNA conformation

PubMed Central

Knecht, Hans; Dobrucki, Jurek; Mai, Sabine

2018-01-01

ABSTRACT Methods of super-resolving light microscopy (SRM) have found an exponentially growing range of applications in cell biology, including nuclear structure analyses. Recent developments have proven that Single Molecule Localization Microscopy (SMLM), a type of SRM, is particularly useful for enhanced spatial analysis of the cell nucleus due to its highest resolving capability combined with very specific fluorescent labeling. In this commentary we offer a brief review of the latest methodological development in the field of SMLM of chromatin designated DNA Structure Fluctuation Assisted Binding Activated Localization Microscopy (abbreviated as fBALM) as well as its potential future applications in biology and medicine. PMID:29297245

Spacer conformation in biologically active molecules. Part 1. Structure and conformational preferences of 2-substituted benzoxazoles

NASA Astrophysics Data System (ADS)

Czylkowski, R.; Karolak-Wojciechowska, J.; Mrozek, A.; Yalçin, I.; Aki-Şener, E.

2001-12-01

The mutual position of two pharmacophoric elements in flexible biologically active molecules depends on the spacer conformation. This is true even for a two-atomic chain put to use as a spacer. It was established for 2-substituted-benzoxazoles containing two aromatic centres joined by -CH2-X- (X=S or O). From crystallographic studies of four molecules it was found that the role of heteroatom is essential for the whole molecule conformation. The spacer with X=S adopts the (-)synclinal conformation while for X=O the (+)antiperiplanar one. Such preferences were also found in the statistical data from Cambridge Structural Database (CSD).

High yield bacterial expression, purification and characterisation of bioactive Human Tousled-like Kinase 1B involved in cancer.

PubMed

Bhoir, Siddhant; Shaik, Althaf; Thiruvenkatam, Vijay; Kirubakaran, Sivapriya

2018-03-19

Human Tousled-like kinases (TLKs) are highly conserved serine/threonine protein kinases responsible for cell proliferation, DNA repair, and genome surveillance. Their possible involvement in cancer via efficient DNA repair mechanisms have made them clinically relevant molecular targets for anticancer therapy. Innovative approaches in chemical biology have played a key role in validating the importance of kinases as molecular targets. However, the detailed understanding of the protein structure and the mechanisms of protein-drug interaction through biochemical and biophysical techniques demands a method for the production of an active protein of exceptional stability and purity on a large scale. We have designed a bacterial expression system to express and purify biologically active, wild-type Human Tousled-like Kinase 1B (hTLK1B) by co-expression with the protein phosphatase from bacteriophage λ. We have obtained remarkably high amounts of the soluble and homogeneously dephosphorylated form of biologically active hTLK1B with our unique, custom-built vector design strategy. The recombinant hTLK1B can be used for the structural studies and may further facilitate the development of new TLK inhibitors for anti-cancer therapy using a structure-based drug design approach.

Chemistry and Pharmacology of Thioflavones.

PubMed

Dong, Jinyun; Zhang, Qijing; Meng, Qingqing; Wang, Zengtao; Li, Shaoshun; Cui, Jiahua

2018-05-15

Thioflavone derivatives are the thio analogs of the core constituent of the natural product class of flavones. Based on the position and oxidation level of sulfur, they can be divided into three major categories: 4-thioflavones, 1-thioflavones and 1-thioflavones 1,1-dioxide. In recent years, great efforts have been made to develop an approach to thioflavones, especially 1-thioflavones with high functional group compatibility, high yields, low toxicity as well as proceeding under a mild condition, and a variety of synthetic protocols have been developed, the method of choice being dependent on the nature of substrates. As isosteric analogs of biologically active flavones, likewise thioflavones exhibit various pharmaceutical properties, such as antimicrobial, anticancer and neuroprotective activities. Replacement of the oxygen atom on flavone skeleton by a sulfur atom resulted in modified biological effects due in most part to the change of structural properties. However, these varying effects depend on the substituents present and the test species. To provide a comprehensive vision of this class of compounds, this review primarily focuses on the structure, synthetic methods, biological properties as well as structure-activity relationships of thioflavones. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synthesis of Novel Aza-aromatic Curcuminoids with Improved Biological Activities towards Various Cancer Cell Lines.

PubMed

Theppawong, Atiruj; Van de Walle, Tim; Grootaert, Charlotte; Bultinck, Margot; Desmet, Tom; Van Camp, John; D'hooghe, Matthias

2018-05-01

Curcumin, a natural compound extracted from the rhizomes of Curcuma longa , displays pronounced anticancer properties but lacks good bioavailability and stability. In a previous study, we initiated structure modification of the curcumin scaffold by imination of the labile β-diketone moiety to produce novel β-enaminone derivatives. These compounds showed promising properties for elaborate follow-up studies. In this work, we focused on another class of nitrogen-containing curcuminoids with a similar objective: to address the bioavailability and stability issues and to improve the biological activity of curcumin. This paper thus reports on the synthesis of new pyridine-, indole-, and pyrrole-based curcumin analogues (aza-aromatic curcuminoids) and discusses their water solubility, antioxidant activity, and antiproliferative properties. In addition, multivariate statistics, including hierarchical clustering analysis and principal component analysis, were performed on a broad set of nitrogen-containing curcuminoids. Compared to their respective mother structures, that is, curcumin and bisdemethoxycurcumin, all compounds, and especially the pyridin-3-yl β-enaminone analogues, showed better water solubility profiles. Interestingly, the pyridine-, indole-, and pyrrole-based curcumin derivatives demonstrated improved biological effects in terms of mitochondrial activity impairment and protein content, in addition to comparable or decreased antioxidant properties. Overall, the biologically active N -alkyl β-enaminone aza-aromatic curcuminoids were shown to offer a desirable balance between good solubility and significant bioactivity.

Rich in life but poor in data: the known knowns and known unknowns of modelling how soil biology drives soil structure

NASA Astrophysics Data System (ADS)

Hallett, Paul; Ogden, Mike

2015-04-01

Soil biology has a fascinating capacity to manipulate pore structure by altering or overcoming hydrological and mechanical properties of soil. Many have postulated, quite rightly, that this capacity of soil biology to 'engineer' its habitat drives its diversity, improves competitiveness and increases resilience to external stresses. A large body of observational research has quantified pore structure evolution accompanied by the growth of organisms in soil. Specific compounds that are exuded by organisms or the biological structures they create have been isolated and found to correlate well with observed changes to pore structure or soil stability. This presentation will provide an overview of basic mechanical and hydrological properties of soil that are affected by biology, and consider missing data that are essential to model how they impact soil structure evolution. Major knowledge gaps that prevent progress will be identified and suggestions will be made of how research in this area should progress. We call for more research to gain a process based understanding of structure formation by biology, to complement observational studies of soil structure before and after imposed biological activity. Significant advancement has already been made in modelling soil stabilisation by plant roots, by combining data on root biomechanics, root-soil interactions and soil mechanical properties. Approaches for this work were developed from earlier materials science and geotechnical engineering research, and the same ethos should be adopted to model the impacts of other biological compounds. Fungal hyphae likely reinforce soils in a similar way to plant roots, with successful biomechanical measurements of these micron diameter structures achieved with micromechanical test frames. Extending root reinforcement models to fungi would not be a straightforward exercise, however, as interparticle bonding and changes to pore water caused by fungal exudates could have a major impact on structure formation and stability. Biological exudates from fungi, bacteria or roots have been found to decrease surface tension and increase viscosity of pore water, with observed impacts to soil strength and water retention. Modelling approaches developed in granular mechanics and geotechnical engineering could be built upon to incorporate biological transformations of hydrological and mechanical properties of soil. With new testing approaches, adapted from materials science, pore scale hydromechanical impacts from biological exudates can be quantified. The research can be complemented with model organisms with differences in biological structures (e.g. root hair mutants), exudation or other properties. Coupled with technological advances that provide 4D imaging of soil structure at relatively rapid capture rates, the potential opportunities to disentangle and model how biology drives soil structure evolution and stability are vast. By quantifying basic soil hydrological and mechanical processes that are driven by soil biology, unknown unknowns may also emerge, providing new insight into how soils function.

Evolution of structural diversity of trichothecene mycotoxins

USDA-ARS?s Scientific Manuscript database

Fungal secondary metabolites (SMs) are diverse in structure and biological activity. Most can be divided into families of analogs that share a core structure but vary in patterns of functional groups (substituents) attached to the core. Typically, fungal genes responsible for synthesis of the same S...

Structural and Chemical Biology of Terpenoid Cyclases

PubMed Central

2017-01-01

The year 2017 marks the twentieth anniversary of terpenoid cyclase structural biology: a trio of terpenoid cyclase structures reported together in 1997 were the first to set the foundation for understanding the enzymes largely responsible for the exquisite chemodiversity of more than 80000 terpenoid natural products. Terpenoid cyclases catalyze the most complex chemical reactions in biology, in that more than half of the substrate carbon atoms undergo changes in bonding and hybridization during a single enzyme-catalyzed cyclization reaction. The past two decades have witnessed structural, functional, and computational studies illuminating the modes of substrate activation that initiate the cyclization cascade, the management and manipulation of high-energy carbocation intermediates that propagate the cyclization cascade, and the chemical strategies that terminate the cyclization cascade. The role of the terpenoid cyclase as a template for catalysis is paramount to its function, and protein engineering can be used to reprogram the cyclization cascade to generate alternative and commercially important products. Here, I review key advances in terpenoid cyclase structural and chemical biology, focusing mainly on terpenoid cyclases and related prenyltransferases for which X-ray crystal structures have informed and advanced our understanding of enzyme structure and function. PMID:28841019

Structures and biological activities of azaphilones produced by Penicillium sp. KCB11A109 from a ginseng field.

PubMed

Son, Sangkeun; Ko, Sung-Kyun; Kim, Jong Won; Lee, Jae Kyoung; Jang, Mina; Ryoo, In-Ja; Hwang, Gwi Ja; Kwon, Min Cheol; Shin, Kee-Sun; Futamura, Yushi; Hong, Young-Soo; Oh, Hyuncheol; Kim, Bo Yeon; Ueki, Masashi; Takahashi, Shunji; Osada, Hiroyuki; Jang, Jae-Hyuk; Ahn, Jong Seog

2016-02-01

Twelve metabolites, including five highly oxygenated azaphilones, geumsanols A-E, along with seven known analogues were isolated from Penicillium sp. KCB11A109, a fungus derived from a ginseng field. Their structures were assigned by spectroscopic means (NMR and MS), and stereochemistries were determined by extensive spectroscopic analyses ((1)H-(1)H coupling constants, NOESY, and HETLOC) and chemical derivatizations (modified Mosher's method and acetonide formation). The isolates were evaluated for their anticancer, antimicrobial, antimalarial activities, and phenotypic effects in zebrafish development. Of these compounds possessing no pyranoquinone core, only geumsanol E exhibited cytotoxic activities and toxic effects on zebrafish embryos, suggesting that a double bond at C-11 and C-12 is important for biological activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Visual event-related potentials to biological motion stimuli in autism spectrum disorders

PubMed Central

Bletsch, Anke; Krick, Christoph; Siniatchkin, Michael; Jarczok, Tomasz A.; Freitag, Christine M.; Bender, Stephan

2014-01-01

Atypical visual processing of biological motion contributes to social impairments in autism spectrum disorders (ASD). However, the exact temporal sequence of deficits of cortical biological motion processing in ASD has not been studied to date. We used 64-channel electroencephalography to study event-related potentials associated with human motion perception in 17 children and adolescents with ASD and 21 typical controls. A spatio-temporal source analysis was performed to assess the brain structures involved in these processes. We expected altered activity already during early stimulus processing and reduced activity during subsequent biological motion specific processes in ASD. In response to both, random and biological motion, the P100 amplitude was decreased suggesting unspecific deficits in visual processing, and the occipito-temporal N200 showed atypical lateralization in ASD suggesting altered hemispheric specialization. A slow positive deflection after 400 ms, reflecting top-down processes, and human motion-specific dipole activation differed slightly between groups, with reduced and more diffuse activation in the ASD-group. The latter could be an indicator of a disrupted neuronal network for biological motion processing in ADS. Furthermore, early visual processing (P100) seems to be correlated to biological motion-specific activation. This emphasizes the relevance of early sensory processing for higher order processing deficits in ASD. PMID:23887808

Relationship between sugar chain structure and biological activity of recombinant human erythropoietin produced in Chinese hamster ovary cells.

PubMed Central

Takeuchi, M; Inoue, N; Strickland, T W; Kubota, M; Wada, M; Shimizu, R; Hoshi, S; Kozutsumi, H; Takasaki, S; Kobata, A

1989-01-01

Two forms of erythropoietin, EPO-bi and EPO-tetra, with different biological activities were isolated from the culture medium of a recombinant Chinese hamster ovary cell line, B8-300, into which the human erythropoietin gene had been introduced. EPO-bi, an unusual form, showed only one-seventh the in vivo activity and 3 times higher in vitro activity of the previously described recombinant human EPO (standard EPO). In contrast, EPO-tetra showed both in vivo and in vitro activities comparable to those of the standard EPO. EPO-bi, EPO-tetra, and the standard EPO had the same amino acid composition and immunoreactivity. However, structural analyses of their N-linked sugar chains revealed that EPO-bi contains the biantennary complex type as the major sugar chain, while EPO-tetra and the standard EPO contain the tetraantennary complex type as the major sugar chain. From examination of various preparations of recombinant human EPO, we found a positive correlation between the in vivo activity of EPO and the ratio of tetraantennary to biantennary oligosaccharides. These results suggest that higher branching of the N-linked sugar chains is essential for effective expression of in vivo biological activity of EPO. PMID:2813359

Returning to Overuse Activity Following a Supraspinatus and Infraspinatus Tear Leads to Joint Damage in a Rat Model

PubMed Central

Reuther, Katherine E.; Thomas, Stephen J.; Evans, Elisabeth F.; Tucker, Jennica J.; Sarver, Joseph J.; Ilkhani-Pour, Sarah; Gray, Chancellor F.; Voleti, Pramod; Glaser, David L.; Soslowsky, Louis J.

2013-01-01

Large rotator cuff tears (supraspinatus and infraspinatus) are common in patients that perform overhead activities (laborers, athletes). In addition, following large cuff tears, these patients commonly attempt to return to pre-injury activity levels. However, there is a limited understanding of the damaging effects on the uninjured joint tissues when doing so. Therefore, the objective of this study was to investigate the effect of returning to overuse activity following a supraspinatus and infraspinatus tear on shoulder function and the structural and biological properties of the intact tendons and glenoid cartilage. Forty rats underwent four weeks of overuse followed by detachment of the supraspinatus and infraspinatus tendons and were then randomized into two groups: return to overuse or cage activity. Ambulatory measurements were performed over time and structural and biologic properties of the adjacent tendons and cartilage were evaluated. Results demonstrated that animals returning to overuse activity did not have altered shoulder function but despite this, did have altered cartilage and tendon properties. These mechanical changes corresponded to altered transcriptional regulation of chondrogenic genes within cartilage and tendon. This study helps define the mechanical and biologic mechanisms leading to joint damage and provides a framework for treating active cuff tear patients. PMID:23764174

Cell-based composite materials with programmed structures and functions

DOEpatents

None

2016-03-01

The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

Cell-based composite materials with programmed structures and functions

DOEpatents

Kaehr, Bryan J.; Brinker, C. Jeffrey; Townson, Jason L.

2018-05-15

The present invention is directed to the use of silicic acid to transform biological materials, including cellular architecture into inorganic materials to provide biocomposites (nanomaterials) with stabilized structure and function. In the present invention, there has been discovered a means to stabilize the structure and function of biological materials, including cells, biomolecules, peptides, proteins (especially including enzymes), lipids, lipid vesicles, polysaccharides, cytoskeletal filaments, tissue and organs with silicic acid such that these materials may be used as biocomposites. In many instances, these materials retain their original biological activity and may be used in harsh conditions which would otherwise destroy the integrity of the biological material. In certain instances, these biomaterials may be storage stable for long periods of time and reconstituted after storage to return the biological material back to its original form. In addition, by exposing an entire cell to form CSCs, the CSCs may function to provide a unique system to study enzymes or a cascade of enzymes which are otherwise unavailable.

A Theoretical Approach to Selection of a Biologically Active Substance in Ultra-Low Doses for Effective Action on a Biological System.

PubMed

Boldyreva, Liudmila Borisovna

2018-05-01

 An approach is offered to selecting a biologically active substance (BAS) in ultra-low dose for effective action on a biological system (BS). The technique is based on the assumption that BAS in ultra-low doses exerts action on BS by means of spin supercurrent emerging between the spin structure created by BAS, on the one hand, and the spin structure created by BS, on the other hand. According to modern quantum-mechanical concepts, these spin structures may be virtual particles pairs having precessing spin (that is, be essentially spin vortices in the physical vacuum) and created by the quantum entities that BAS and BS consist of. The action is effective provided there is equality of precession frequencies of spins in these spin structures.  In this work, some methods are considered for determining the precession frequencies of spins in virtual particles pairs: (1) determination of energy levels of quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of the virtual particles pair spin, the effect being initiated by action of magnetic vector potential (the spin-flip effect takes place when the varied frequency of the magnetic vector potential equals the precession frequency of the spin); (3) determining the frequencies of photons effectively acting on BS.  It is shown that the effect of BAS in ultra-low doses on BS can be replaced by the effect of a beam of low-intensity photons, if the frequency of photons equals the precession frequency of spin in spin structures created by BS. Consequently, the color of bodies placed near a biological system is able to exert an effective action on the biological system: that is "color therapy" is possible. It is also supposed that the spin-flip effect may be used not only for determining the precession frequency of spin in spin structures created by BS but also for therapeutic action on biological systems. The Faculty of Homeopathy.

Numerical simulation on the adaptation of forms in trabecular bone to mechanical disuse and basic multi-cellular unit activation threshold at menopause

NASA Astrophysics Data System (ADS)

Gong, He; Fan, Yubo; Zhang, Ming

2008-04-01

The objective of this paper is to identify the effects of mechanical disuse and basic multi-cellular unit (BMU) activation threshold on the form of trabecular bone during menopause. A bone adaptation model with mechanical- biological factors at BMU level was integrated with finite element analysis to simulate the changes of trabecular bone structure during menopause. Mechanical disuse and changes in the BMU activation threshold were applied to the model for the period from 4 years before to 4 years after menopause. The changes in bone volume fraction, trabecular thickness and fractal dimension of the trabecular structures were used to quantify the changes of trabecular bone in three different cases associated with mechanical disuse and BMU activation threshold. It was found that the changes in the simulated bone volume fraction were highly correlated and consistent with clinical data, and that the trabecular thickness reduced significantly during menopause and was highly linearly correlated with the bone volume fraction, and that the change trend of fractal dimension of the simulated trabecular structure was in correspondence with clinical observations. The numerical simulation in this paper may help to better understand the relationship between the bone morphology and the mechanical, as well as biological environment; and can provide a quantitative computational model and methodology for the numerical simulation of the bone structural morphological changes caused by the mechanical environment, and/or the biological environment.

Chemical Properties of Caffeic and Ferulic Acids in Biological System: Implications in Cancer Therapy. A Review.

PubMed

Damasceno, Sarah S; Dantas, Bruna B; Ribeiro-Filho, Jaime; Antônio M Araújo, Demetrius; Galberto M da Costa, José

2017-01-01

The antioxidant properties of caffeic and ferulic acids in biological systems have been extensively demonstrated. As antioxidants, these compounds prevent the production of reactive oxygen species (ROS), which cause cell lesions that are associated with the development of several diseases, including cancer. Recent findings suggest that the chemoprotective action of these phenolic acids occurs through the following mechanisms: regulation of gene expression, chelation and / or reduction of transition metals, formation of covalent adducts and direct toxicity. The biological efficacy of these promising chemoprotective agents is strongly related with their chemical structure. Therefore, in this study, we discuss the structural characteristics of ferulic and caffeic acids that are responsible for their biological activities, as well as the mechanisms of action involved with the anti-cancer activity. Several reports indicated that the antioxidant effect of these phenylpropanoids results from reactions with free radicals with formation of stable products in the cells. The chelating effect of these compounds was also reported as an important protective mechanism against oxidative. Finally, the lipophilicity of these agents facilitates their entry into the cells, and thus, contributes to the anticancer activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Structural Stereochemistry of Androstene Hormones Determines Interactions with Human Androgen, Estrogen, and Glucocorticoid Receptors

PubMed Central

Shaak, Thomas L.; Wijesinghe, Dayanjan S.; Chalfant, Charles E.; Diegelmann, Robert F.; Ward, Kevin R.; Loria, Roger M.

2013-01-01

DHEA, 17α-AED, 17β-AED, and 17β-AET exhibit strong biological activity that has been attributed to androgenic, estrogenic, or antiglucocorticoid activity in vivo and in vitro. This study compared DHEA, 17α-AED, 17β-AED, and 17β-AET for their ability to activate the human AR, ER, and GR and determine the relative androgenicity, estrogenicity, and glucocorticoid activity. The results show that, at the receptor level, these androstene hormones are weak AR and even weaker ER activators. Direct androstene hormone activation of the human AR, ERα, and ERβ may not be essential for their biological function. Similarly, these hormones indirectly activated the human GR, only in the presence of high dexamethasone concentrations. These results underscore the major difference between androstene hormone interactions with these nuclear receptors and their biological effects. PMID:24729874

Chemistry and Biological Activities of Flavonoids: An Overview

PubMed Central

Kumar, Shashank; Pandey, Abhay K.

2013-01-01

There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production. PMID:24470791

Normal form from biological motion despite impaired ventral stream function.

PubMed

Gilaie-Dotan, S; Bentin, S; Harel, M; Rees, G; Saygin, A P

2011-04-01

We explored the extent to which biological motion perception depends on ventral stream integration by studying LG, an unusual case of developmental visual agnosia. LG has significant ventral stream processing deficits but no discernable structural cortical abnormality. LG's intermediate visual areas and object-sensitive regions exhibit abnormal activation during visual object perception, in contrast to area V5/MT+ which responds normally to visual motion (Gilaie-Dotan, Perry, Bonneh, Malach, & Bentin, 2009). Here, in three studies we used point light displays, which require visual integration, in adaptive threshold experiments to examine LG's ability to detect form from biological and non-biological motion cues. LG's ability to detect and discriminate form from biological motion was similar to healthy controls. In contrast, he was significantly deficient in processing form from non-biological motion. Thus, LG can rely on biological motion cues to perceive human forms, but is considerably impaired in extracting form from non-biological motion. Finally, we found that while LG viewed biological motion, activity in a network of brain regions associated with processing biological motion was functionally correlated with his V5/MT+ activity, indicating that normal inputs from V5/MT+ might suffice to activate his action perception system. These results indicate that processing of biologically moving form can dissociate from other form processing in the ventral pathway. Furthermore, the present results indicate that integrative ventral stream processing is necessary for uncompromised processing of non-biological form from motion. Copyright © 2011 Elsevier Ltd. All rights reserved.

Teaching Flower Structure & Floral Formulae--A Mix of the Real & Virtual Worlds

ERIC Educational Resources Information Center

Burrows, Geoff

2010-01-01

The study of flower structure is essential in plant identification and in understanding sexual reproduction in plants, pollination syndromes, plant breeding, and fruit structure. Thus, study of flower structure and construction of floral formulae are standard parts of first-year university botany and biology courses. These activities involve…

Biomedical and Catalytic Opportunities of Virus-Like Particles in Nanotechnology

PubMed Central

Schwarz, B.; Uchida, M.; Douglas, T.

2016-01-01

Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials’ assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials. PMID:28057256

Influence of culture medium growth variables on Ganoderma lucidum exopolysaccharides structural features.

PubMed

Fraga, Irene; Coutinho, João; Bezerra, Rui M; Dias, Albino A; Marques, Guilhermina; Nunes, Fernando M

2014-10-13

In this work the effect of carbon and nitrogen levels and initial pH of the wheat extract culture medium of submerged culture of Ganoderma lucidum on the amount, purity and structural features of exopolysaccharides (EPS) were studied. A low peptone level (1.65 g L(-1)) favored mycelium biomass, EPS purity, but a higher supply of peptone (4.80 g L(-1)) is needed for maximum EPS production. The carbohydrate composition of the EPS and structural features also changed significantly according to the different growing conditions, being observed significant differences in the (1 → 3)/(1 → 4)-Glcp ratio and also on the branching degree of EPS. As the biological activities of EPS are highly dependent on the polysaccharide structural features, this variability can have implications on the EPS biological activities, but can also be used advantageously to produce tailor made polysaccharides with specific applications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure Biology of Membrane Bound Enzymes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fu, Dax

The overall goal of the proposed research is to understand the membrane-associated active processes catalyzed by an alkanemore » $$\\square$$-hydroxylase (AlkB) from eubacterium Pseudomonase oleovorans. AlkB performs oxygenation of unactivated hydrocarbons found in crude oils. The enzymatic reaction involves energy-demanding steps in the membrane with the uses of structurally unknown metal active sites featuring a diiron [FeFe] center. At present, a critical barrier to understanding the membrane-associated reaction mechanism is the lack of structural information. The structural biology efforts have been challenged by technical difficulties commonly encountered in crystallization and structural determination of membrane proteins. The specific aims of the current budget cycle are to crystalize AlkB and initiate X-ray analysis to set the stage for structural determination. The long-term goals of our structural biology efforts are to provide an atomic description of AlkB structure, and to uncover the mechanisms of selective modification of hydrocarbons. The structural information will help elucidating how the unactivated C-H bonds of saturated hydrocarbons are oxidized to initiate biodegradation and biotransformation processes. The knowledge gained will be fundamental to biotechnological applications to biofuel transformation of non-edible oil feedstock. Renewable biodiesel is a promising energy carry that can be used to reduce fossil fuel dependency. The proposed research capitalizes on prior BES-supported efforts on over-expression and purification of AlkB to explore the inner workings of a bioenergy-relevant membrane-bound enzyme.« less

Challenges and complexity of functionality evaluation of flavan-3-ol derivatives.

PubMed

Saito, Akiko

2017-06-01

Flavan-3-ol derivatives are common plant-derived bioactive compounds. In particular, (-)-epigallocatechin-3-O-gallate shows various moderate biological activities without severe toxicity, and its health-promoting effects have been widely studied because it is a main ingredient in green tea and is commercially available at low cost. Although various biologically active flavan-3-ol derivatives are present as minor constituents in plants as well as in green tea, their biological activities have yet to be revealed, mainly due to their relative unavailability. Here, I outline the major factors contributing to the complexity of functionality studies of flavan-3-ol derivatives, including proanthocyanidins and oligomeric flavan-3-ols. I emphasize the importance of conducting structure-activity relationship studies using synthesized flavan-3-ol derivatives that are difficult to obtain from plant extracts in pure form to overcome this challenge. Further discovery of these minor constituents showing strong biological activities is expected to produce useful information for the development of functional health foods.

DNA in a Tunnel: A Comfy Spot for Recognition - or -The Structure of BsoBI Complexed with DNA. What can we Learn about Function via Structure Determination and how can this be Applied to Bone or Muscle Biology?

NASA Technical Reports Server (NTRS)

vanderWoerd, Mark

2004-01-01

The structure and function of a biologically active molecule are related. To understand its function, it is necessary (but not always sufficient) to know the structure of the molecule. There are many ways of relating the molecular function with the structure. Mutation analysis can identify pertinent amino acids of an enzyme, or alternatively structure comparison of the of two similar molecules with different function may lead to understanding which parts are responsible for a functional aspect, or a series of "structural cartoons" - enzyme structure, enzyme plus substrate, enzyme with transition state analog, and enzyme with product - may give insight in the function of a molecule. As an example we will discuss the structure and function of the restriction enzyme BsoBI from Bacillus stearothemzophilus in complex with its cognate DNA. The enzyme forms a unique complex with DNA in that it completely encircles the DNA. The structure reveals the enzyme-DNA contacts, how the DNA is distorted compared with the canonical forms, and elegantly shows how two distinct DNA sequences can be recognized with the same efficiency. Based on the structure we may also propose a hypothesis how the enzymatic mechanism works. The knowledge gained thru studies such as this one can be used to alter the function by changing the molecular structure. Usually this is done by design of inhibitors specifically active against and fitting into an active site of the enzyme of choice. In the case of BsoBI one of the objectives of the study was to alter the enzyme specificity. In bone biology there are many candidates available for molecular study in order to explain, alter, or (temporarily) suspend activity. For example, the understanding of a pathway that negatively regulates bone formation may be a good target for drug design to stimulate bone formation and have good potential as the basis for new countermeasures against bone loss. In principle the same approach may aid muscle atrophy, radiation damage, immune response changes and other risks identified for long-duration Space travel.

Effect of atmospheric pressure dielectric barrier discharge plasma on the biological activity of naringin.

PubMed

Kim, Hyun-Joo; Yong, Hae In; Park, Sanghoo; Kim, Kijung; Kim, Tae Hoon; Choe, Wonho; Jo, Cheorun

2014-10-01

The biological activity of naringin treated with atmospheric pressure plasma was evaluated to investigate whether exposure to plasma can be used as a method to improve the biological activity of natural materials. Naringin was dissolved in methanol (at 500 ppm) and transferred to a container. A dielectric barrier discharge (DBD) (250 W, 15 kHz, ambient air) was then generated. Treatment with the plasma for 20 min increased the radical-scavenging activity, FRAP value, and the total phenolic compound content of naringin from 1.45% to 38.20%, from 27.78 to 207.78 μM/g, and from 172.50 to 225.83 ppm, respectively. Moreover, the tyrosinase-inhibition effect of naringin increased from 6.12% to 83.30% upon plasma treatment. Naringin treated with plasma exhibited antimicrobial activity against foodborne pathogens, especially Salmonella Typhimurium; an activity that was absent before plasma treatment. Structural modifications induced in the naringin molecule by plasma might be responsible for improving the biological activity of naringin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rationally designed mutations convert complexes of human recombinant T cell receptor ligands into monomers that retain biological activity

PubMed Central

Huan, Jianya Y; Meza-Romero, Roberto; Mooney, Jeffery L; Chou, Yuan K; Edwards, David M; Rich, Cathleen; Link, Jason M; Vandenbark, Arthur A; Bourdette, Dennis N; Bächinger, Hans-Peter; Burrows, Gregory G

2012-01-01

Single-chain human recombinant T cell receptor ligands derived from the peptide binding/TCR recognition domain of human HLA-DR2b (DRA*0101/DRB1*1501) produced in Escherichia coli with and without amino-terminal extensions containing antigenic peptides have been described previously. While molecules with the native sequence retained biological activity, they formed higher order aggregates in solution. In this study, we used site-directed mutagenesis to modify the β-sheet platform of the DR2-derived RTLs, obtaining two variants that were monomeric in solution by replacing hydrophobic residues with polar (serine) or charged (aspartic acid) residues. Size exclusion chromatography and dynamic light scattering demonstrated that the modified RTLs were monomeric in solution, and structural characterization using circular dichroism demonstrated the highly ordered secondary structure of the RTLs. Peptide binding to the `empty' RTLs was quantified using biotinylated peptides, and functional studies showed that the modified RTLs containing covalently tethered peptides were able to inhibit antigen-specific T cell proliferation in vitro, as well as suppress experimental autoimmune encephalomyelitis in vivo. These studies demonstrated that RTLs encoding the Ag-binding/TCR recognition domain of MHC class II molecules are innately very robust structures, capable of retaining potent biological activity separate from the Ig-fold domains of the progenitor class II structure, with prevention of aggregation accomplished by modification of an exposed surface that was buried in the progenitor structure. PMID:22973070

DNA Structure.

ERIC Educational Resources Information Center

Henderson, Paula

This autoinstructional lesson deals with the study of molecular biology. It is suggested as relevant to high school biology courses. No prerequisites are suggested. Two behavioral objectives are given leading to the learning of nucleotide bases, their parts, and the ways they pair as they do. The time suggested for this learning activity is about…

An Undergraduate Laboratory Activity on Molecular Dynamics Simulations

ERIC Educational Resources Information Center

Spitznagel, Benjamin; Pritchett, Paige R.; Messina, Troy C.; Goadrich, Mark; Rodriguez, Juan

2016-01-01

Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we…

Why Do We Keep Catching the Common Cold?

ERIC Educational Resources Information Center

Gillen, Alan L.; Mayor, Heather D.

1995-01-01

Describes activities for biology teachers that will stimulate discussions on virus structure, cell biology, rhino viruses, and new trends in treating the common cold. Provides opportunity for inquiry and problem solving in exercises that emphasize an understanding of how common cold viruses might pack inside nasal epithelial cells. (14 references)…

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions.

PubMed

Tran, Tran T; Kulis, Christina; Long, Steven M; Bryant, Darryn; Adams, Peter; Smythe, Mark L

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

Defining scaffold geometries for interacting with proteins: geometrical classification of secondary structure linking regions

NASA Astrophysics Data System (ADS)

Tran, Tran T.; Kulis, Christina; Long, Steven M.; Bryant, Darryn; Adams, Peter; Smythe, Mark L.

2010-11-01

Medicinal chemists synthesize arrays of molecules by attaching functional groups to scaffolds. There is evidence suggesting that some scaffolds yield biologically active molecules more than others, these are termed privileged substructures. One role of the scaffold is to present its side-chains for molecular recognition, and biologically relevant scaffolds may present side-chains in biologically relevant geometries or shapes. Since drug discovery is primarily focused on the discovery of compounds that bind to proteinaceous targets, we have been deciphering the scaffold shapes that are used for binding proteins as they reflect biologically relevant shapes. To decipher the scaffold architecture that is important for binding protein surfaces, we have analyzed the scaffold architecture of protein loops, which are defined in this context as continuous four residue segments of a protein chain that are not part of an α-helix or β-strand secondary structure. Loops are an important molecular recognition motif of proteins. We have found that 39 clusters reflect the scaffold architecture of 89% of the 23,331 loops in the dataset, with average intra-cluster and inter-cluster RMSD of 0.47 and 1.91, respectively. These protein loop scaffolds all have distinct shapes. We have used these 39 clusters that reflect the scaffold architecture of protein loops as biological descriptors. This involved generation of a small dataset of scaffold-based peptidomimetics. We found that peptidomimetic scaffolds with reported biological activities matched loop scaffold geometries and those peptidomimetic scaffolds with no reported biologically activities did not. This preliminary evidence suggests that organic scaffolds with tight matches to the preferred loop scaffolds of proteins, implies the likelihood of the scaffold to be biologically relevant.

The dimer interface of the membrane type 1 matrix metalloproteinase hemopexin domain: crystal structure and biological functions.

PubMed

Tochowicz, Anna; Goettig, Peter; Evans, Richard; Visse, Robert; Shitomi, Yasuyuki; Palmisano, Ralf; Ito, Noriko; Richter, Klaus; Maskos, Klaus; Franke, Daniel; Svergun, Dmitri; Nagase, Hideaki; Bode, Wolfram; Itoh, Yoshifumi

2011-03-04

Homodimerization is an essential step for membrane type 1 matrix metalloproteinase (MT1-MMP) to activate proMMP-2 and to degrade collagen on the cell surface. To uncover the molecular basis of the hemopexin (Hpx) domain-driven dimerization of MT1-MMP, a crystal structure of the Hpx domain was solved at 1.7 Å resolution. Two interactions were identified as potential biological dimer interfaces in the crystal structure, and mutagenesis studies revealed that the biological dimer possesses a symmetrical interaction where blades II and III of molecule A interact with blades III and II of molecule B. The mutations of amino acids involved in the interaction weakened the dimer interaction of Hpx domains in solution, and incorporation of these mutations into the full-length enzyme significantly inhibited dimer-dependent functions on the cell surface, including proMMP-2 activation, collagen degradation, and invasion into the three-dimensional collagen matrix, whereas dimer-independent functions, including gelatin film degradation and two-dimensional cell migration, were not affected. These results shed light on the structural basis of MT1-MMP dimerization that is crucial to promote cellular invasion.

Rapid Scanning Structure-Activity Relationships in Combinatorial Data Sets: Identification of Activity Switches

PubMed Central

Medina-Franco, José L.; Edwards, Bruce S.; Pinilla, Clemencia; Appel, Jon R.; Giulianotti, Marc A.; Santos, Radleigh G.; Yongye, Austin B.; Sklar, Larry A.; Houghten, Richard A.

2013-01-01

We present a general approach to describe the structure-activity relationships (SAR) of combinatorial data sets with activity for two biological endpoints with emphasis on the rapid identification of substitutions that have a large impact on activity and selectivity. The approach uses Dual-Activity Difference (DAD) maps that represent a visual and quantitative analysis of all pairwise comparisons of one, two, or more substitutions around a molecular template. Scanning the SAR of data sets using DAD maps allows the visual and quantitative identification of activity switches defined as specific substitutions that have an opposite effect on the activity of the compounds against two targets. The approach also rapidly identifies single- and double-target R-cliffs, i.e., compounds where a single or double substitution around the central scaffold dramatically modifies the activity for one or two targets, respectively. The approach introduced in this report can be applied to any analogue series with two biological activity endpoints. To illustrate the approach, we discuss the SAR of 106 pyrrolidine bis-diketopiperazines tested against two formylpeptide receptors obtained from positional scanning deconvolution methods of mixture-based libraries. PMID:23705689

Indonesian propolis: chemical composition, biological activity and botanical origin.

PubMed

Trusheva, Boryana; Popova, Milena; Koendhori, Eko Budi; Tsvetkova, Iva; Naydenski, Christo; Bankova, Vassya

2011-03-01

From a biologically active extract of Indonesian propolis from East Java, 11 compounds were isolated and identified: four alk(en)ylresorcinols (obtained as an inseparable mixture) (1-4) were isolated for the first time from propolis, along with four prenylflavanones (6-9) and three cycloartane-type triterpenes (5, 10 and 11). The structures of the components were elucidated based on their spectral properties. All prenylflavanones demonstrated significant radical scavenging activity against diphenylpicrylhydrazyl radicals, and compound 6 showed significant antibacterial activity against Staphylococcus aureus. For the first time Macaranga tanarius L. and Mangifera indica L. are shown as plant sources of Indonesian propolis.

Synthesis and antioxidant activity of curcumin analogs.

PubMed

Zheng, Qu-Tong; Yang, Ze-Hua; Yu, Liu-Ying; Ren, Yu-Yan; Huang, Qiu-Xia; Liu, Qiu; Ma, Xiang-Yu; Chen, Zi-Kang; Wang, Zong-Bao; Zheng, Xing

2017-05-01

Numerous biological activities including antioxidant, antitumor, anti-inflammation, and antivirus of the natural product curcumin were reported. However, the clinical application of it was significantly limited by its instability, poor solubility, less body absorbing, and low bioavailability. This review focuses on the structure modification and antioxidant activity evaluation of curcumin. To study the structure-activity relationship (SAR), five series of curcumin analogs were synthesized and their antioxidant activity were evaluated in vitro. The results showed that electron-donating groups, especially the phenolic hydroxyl group are an essential component to improve the antioxidant activity.

Acenaphthenequinone thiosemicarbazone and its transition metal complexes: synthesis, structure, and biological activity.

PubMed

Rodriguez-Argüelles, M C; Belicchi Ferrari, M; Gasparri Fava, G; Pelizzi, C; Pelosi, G; Albertini, R; Bonati, A; Dall'Aglio, P P; Lunghi, P; Pinelli, S

1997-04-01

The reaction of iron, nickel, copper, and zinc chlorides or acetates with acenaphthenequinone thiosemicarbazone, Haqtsc leads to the formation of novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the free ligand Haqtsc 1 and of the compound [Ni(aqtsc)2].DMF 2, have also been determined by X-ray methods from diffractometer data. In 1, the conformation of the two nonequivalent molecules is governed by intramolecular hydrogen bonds, while an intermolecular hydrogen bond is responsible for dimer-like groups formation. In 2, the coordination geometry about nickel is distorted octahedral, and the two ligand molecules are terdentate monodeprotonated. Biological studies have shown that, for the first time at least up the used doses, a free ligand is active both in the inhibition of cell proliferation and in the induced differentiation on Friend erythroleukemia cells (FLC).

Monoalkylated barbiturate derivatives: X-ray crystal structure, theoretical studies, and biological activities

NASA Astrophysics Data System (ADS)

Barakat, Assem; Al-Majid, Abdullah Mohammed; Soliman, Saied M.; Islam, Mohammad Shahidul; Ghawas, Hussain Mansur; Yousuf, Sammer; Choudhary, M. Iqbal; Wadood, Abdul

2017-08-01

Barbiturate derivatives are privileged structures with a broad range of pharmaceutical applications. We prepared a series of 5-monoalkylated barbiturate derivatives (3a-l) and evaluated, in vitro, their antioxidant (DPPH assay), and α-glucosidase inhibitory activities. Compounds 3a-l were synthesized via Michael addition. The structure of compound 3k was determined using X-ray single-crystal diffraction, and geometric parameters were calculated using density functional theory at the B3LYP/6-311G(d,p) level of theory. Further, the structural analysis of 3k were also investigated. Biological studies revealed that compounds 3b (IC50 = 133.1 ± 3.2 μM), 3d (IC50 = 305 ± 7.7 μM), and 3e (IC50 = 184 ± 2.3 μM) have potent α-glucosidase enzyme inhibitors and showed greater activity than the standard drug acarbose (IC50 = 841 ± 1.73 μM). Compounds 3a-3i were found to show weak antioxidant activity against 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radicals (IC50 = 91 ± 0.75 to 122 ± 1.0 μM) when tested against a standard antioxidant, gallic acid (IC50 = 23 ± 0.43 μM).

Structure-activity relationship of karrikin germination stimulants.

PubMed

Flematti, Gavin R; Scaffidi, Adrian; Goddard-Borger, Ethan D; Heath, Charles H; Nelson, David C; Commander, Lucy E; Stick, Robert V; Dixon, Kingsley W; Smith, Steven M; Ghisalberti, Emilio L

2010-08-11

Karrikins (2H-furo[2,3-c]pyran-2-ones) are potent smoke-derived germination promoters for a diverse range of plant species but, to date, their mode of action remains unknown. This paper reports the structure-activity relationship of numerous karrikin analogues to increase understanding of the key structural features of the molecule that are required for biological activity. The results demonstrate that modification at the C5 position is preferred over modification at the C3, C4, or C7 positions for retaining the highest bioactivity.

Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

PubMed

Dong, Zheng; Zhou, Hongyu; Tao, Peng

2018-02-01

PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

Brain processing of biologically relevant odors in the awake rat, as revealed by manganese-enhanced MRI.

PubMed

Lehallier, Benoist; Rampin, Olivier; Saint-Albin, Audrey; Jérôme, Nathalie; Ouali, Christian; Maurin, Yves; Bonny, Jean-Marie

2012-01-01

So far, an overall view of olfactory structures activated by natural biologically relevant odors in the awake rat is not available. Manganese-enhanced MRI (MEMRI) is appropriate for this purpose. While MEMRI has been used for anatomical labeling of olfactory pathways, functional imaging analyses have not yet been performed beyond the olfactory bulb. Here, we have used MEMRI for functional imaging of rat central olfactory structures and for comparing activation maps obtained with odors conveying different biological messages. Odors of male fox feces and of chocolate flavored cereals were used to stimulate conscious rats previously treated by intranasal instillation of manganese (Mn). MEMRI activation maps showed Mn enhancement all along the primary olfactory cortex. Mn enhancement elicited by male fox feces odor and to a lesser extent that elicited by chocolate odor, differed from that elicited by deodorized air. This result was partly confirmed by c-Fos immunohistochemistry in the piriform cortex. By providing an overall image of brain structures activated in awake rats by odorous stimulation, and by showing that Mn enhancement is differently sensitive to different stimulating odors, the present results demonstrate the interest of MEMRI for functional studies of olfaction in the primary olfactory cortex of laboratory small animals, under conditions close to natural perception. Finally, the factors that may cause the variability of the MEMRI signal in response to different odor are discussed.

New Insights in Thrombin Inhibition Structure-Activity Relationships by Characterization of Octadecasaccharides from Low Molecular Weight Heparin.

PubMed

Mourier, Pierre A J; Guichard, Olivier Y; Herman, Fréderic; Sizun, Philippe; Viskov, Christian

2017-03-08

Low Molecular Weight Heparins (LMWH) are complex anticoagulant drugs that mainly inhibit the blood coagulation cascade through indirect interaction with antithrombin. While inhibition of the factor Xa is well described, little is known about the polysaccharide structure inhibiting thrombin. In fact, a minimal chain length of 18 saccharides units, including an antithrombin (AT) binding pentasaccharide, is mandatory to form the active ternary complex for LMWH obtained by alkaline β-elimination (e.g., enoxaparin). However, the relationship between structure of octadecasaccharides and their thrombin inhibition has not been yet assessed on natural compounds due to technical hurdles to isolate sufficiently pure material. We report the preparation of five octadecasaccharides by using orthogonal separation methods including size exclusion, AT affinity, ion pairing and strong anion exchange chromatography. Each of these octadecasaccharides possesses two AT binding pentasaccharide sequences located at various positions. After structural elucidation using enzymatic sequencing and NMR, in vitro aFXa and aFIIa were determined. The biological activities reveal the critical role of each pentasaccharide sequence position within the octadecasaccharides and structural requirements to inhibit thrombin. Significant differences in potency, such as the twenty-fold magnitude difference observed between two regioisomers, further highlights the importance of depolymerisation process conditions on LMWH biological activity.

Synthesis of N-(6-Arylbenzo[d]thiazole-2-acetamide Derivatives and Their Biological Activities: An Experimental and Computational Approach.

PubMed

Gull, Yasmeen; Rasool, Nasir; Noreen, Mnaza; Altaf, Ataf Ali; Musharraf, Syed Ghulam; Zubair, Muhammad; Nasim, Faiz-Ul-Hassan; Yaqoob, Asma; DeFeo, Vincenzo; Zia-Ul-Haq, Muhammad

2016-02-25

A new series of N-(6-arylbenzo[d]thiazol-2-yl)acetamides were synthesized by C-C coupling methodology in the presence of Pd(0) using various aryl boronic pinacol ester/acids. The newly synthesized compounds were evaluated for various biological activities like antioxidant, haemolytic, antibacterial and urease inhibition. In bioassays these compounds were found to have moderate to good activities. Among the tested biological activities screened these compounds displayed the most significant activity for urease inhibition. In urease inhibition, all compounds were found more active than the standard used. The compound N-(6-(p-tolyl)benzo[d]thiazol-2-yl)acetamide was found to be the most active. To understand this urease inhibition, molecular docking studies were performed. The in silico studies showed that these acetamide derivatives bind to the non-metallic active site of the urease enzyme. Structure-activity studies revealed that H-bonding of compounds with the enzyme is important for its inhibition.

[Studies on the structure-activity relationship of retinoids--Hansch analysis and 3D-OSAR studies on specific ligands of retinoid x receptor].

PubMed

Huang, N; Chu, F; Guo, Z

1998-06-01

Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retinoids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitative structure-activity relationships of specific ligands of RXR, we carried out mimesis of environment of ligands interacting with their receptor and, to some extent, mapping the topological and physico-chemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.

Increased structure and active learning reduce the achievement gap in introductory biology.

PubMed

Haak, David C; HilleRisLambers, Janneke; Pitre, Emile; Freeman, Scott

2011-06-03

Science, technology, engineering, and mathematics instructors have been charged with improving the performance and retention of students from diverse backgrounds. To date, programs that close the achievement gap between students from disadvantaged versus nondisadvantaged educational backgrounds have required extensive extramural funding. We show that a highly structured course design, based on daily and weekly practice with problem-solving, data analysis, and other higher-order cognitive skills, improved the performance of all students in a college-level introductory biology class and reduced the achievement gap between disadvantaged and nondisadvantaged students--without increased expenditures. These results support the Carnegie Hall hypothesis: Intensive practice, via active-learning exercises, has a disproportionate benefit for capable but poorly prepared students.

Acetylated Triterpene Glycosides and Their Biological Activity from Holothuroidea Reported in the Past Six Decades

PubMed Central

Bahrami, Yadollah; Franco, Christopher M. M.

2016-01-01

Sea cucumbers have been valued for many centuries as a tonic and functional food, dietary delicacies and important ingredients of traditional medicine in many Asian countries. An assortment of bioactive compounds has been described in sea cucumbers. The most important and abundant secondary metabolites from sea cucumbers are triterpene glycosides (saponins). Due to the wide range of their potential biological activities, these natural compounds have gained attention and this has led to their emergence as high value compounds with extended application in nutraceutical, cosmeceutical, medicinal and pharmaceutical products. They are characterized by bearing a wide spectrum of structures, such as sulfated, non-sulfated and acetylated glycosides. Over 700 triterpene glycosides have been reported from the Holothuroidea in which more than 145 are decorated with an acetoxy group having 38 different aglycones. The majority of sea cucumber triterpene glycosides are of the holostane type containing a C18 (20) lactone group and either Δ7(8) or Δ9(11) double bond in their genins. The acetoxy group is mainly connected to the C-16, C-22, C-23 and/or C-25 of their aglycone. Apparently, the presence of an acetoxy group, particularly at C-16 of the aglycone, plays a significant role in the bioactivity; including induction of caspase, apoptosis, cytotoxicity, anticancer, antifungal and antibacterial activities of these compounds. This manuscript highlights the structure of acetylated saponins, their biological activity, and their structure-activity relationships. PMID:27527190

A Structured Viroid RNA Serves as a Substrate for Dicer-Like Cleavage To Produce Biologically Active Small RNAs but Is Resistant to RNA-Induced Silencing Complex-Mediated Degradation▿

PubMed Central

Itaya, Asuka; Zhong, Xuehua; Bundschuh, Ralf; Qi, Yijun; Wang, Ying; Takeda, Ryuta; Harris, Ann R.; Molina, Carlos; Nelson, Richard S.; Ding, Biao

2007-01-01

RNA silencing is a potent means of antiviral defense in plants and animals. A hallmark of this defense response is the production of 21- to 24-nucleotide viral small RNAs via mechanisms that remain to be fully understood. Many viruses encode suppressors of RNA silencing, and some viral RNAs function directly as silencing suppressors as counterdefense. The occurrence of viroid-specific small RNAs in infected plants suggests that viroids can trigger RNA silencing in a host, raising the question of how these noncoding and unencapsidated RNAs survive cellular RNA-silencing systems. We address this question by characterizing the production of small RNAs of Potato spindle tuber viroid (srPSTVds) and investigating how PSTVd responds to RNA silencing. Our molecular and biochemical studies provide evidence that srPSTVds were derived mostly from the secondary structure of viroid RNAs. Replication of PSTVd was resistant to RNA silencing, although the srPSTVds were biologically active in guiding RNA-induced silencing complex (RISC)-mediated cleavage, as shown with a sensor system. Further analyses showed that without possessing or triggering silencing suppressor activities, the PSTVd secondary structure played a critical role in resistance to RISC-mediated cleavage. These findings support the hypothesis that some infectious RNAs may have evolved specific secondary structures as an effective means to evade RNA silencing in addition to encoding silencing suppressor activities. Our results should have important implications in further studies on RNA-based mechanisms of host-pathogen interactions and the biological constraints that shape the evolution of infectious RNA structures. PMID:17202210

Novel Structures of Self-Associating Stapled Peptides

PubMed Central

Bhattacharya, Shibani; Zhang, Hongtao; Cowburn, David; Debnath, Asim K.

2012-01-01

Hydrocarbon stapling of peptides is a powerful technique to transform linear peptides into cell-permeable helical structures that can bind to specific biological targets. In this study, we have used high resolution solution NMR techniques complemented by Dynamic Light Scattering to characterize extensively a family of hydrocarbon stapled peptides with known inhibitory activity against HIV-1 capsid assembly to evaluate the various factors that modulate activity. The helical peptides share a common binding motif but differ in charge, the length and position of the staple. An important outcome of the study was to show the peptides share a propensity to self-associate into organized polymeric structures mediated predominantly by hydrophobic interactions between the olefinic chain and the aromatic side-chains from the peptide. We have also investigated in detail the structural significance of the length and position of the staple, and of olefinic bond isomerization in stabilizing the helical conformation of the peptides as potential factors driving polymerization. This study presents the numerous challenges of designing biologically active stapled peptides and the conclusions have broad implications for optimizing a promising new class of compounds in drug discovery. PMID:22170623

Identification of three critical regions within mouse interleukin 2 by fine structural deletion analysis.

PubMed Central

Zurawski, S M; Zurawski, G

1988-01-01

We have analyzed structure--function relationships of the protein hormone murine interleukin 2 by fine structural deletion mapping. A total of 130 deletion mutant proteins, together with some substitution and insertion mutant proteins, was expressed in Escherichia coli and analyzed for their ability to sustain the proliferation of a cloned murine T cell line. This analysis has permitted a functional map of the protein to be drawn and classifies five segments of the protein, which together contain 48% of the sequence, as unessential to the biological activity of the protein. A further 26% of the protein is classified as important, but not crucial, for the activity. Three regions, consisting of amino acids 32-35, 66-77 and 119-141 contain the remaining 26% of the protein and are critical to the biological activity of the protein. The functional map is discussed in the context of the possible role of the identified critical regions in the structure of the hormone and its binding to the interleukin 2 receptor complex. Images PMID:3261239

TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan indigenous plants.

PubMed

Tung, Chun-Wei; Lin, Ying-Chi; Chang, Hsun-Shuo; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng

2014-01-01

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure-activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein-ligand docking. Database URL: http://cwtung.kmu.edu.tw/tipdb. © The Author(s) 2014. Published by Oxford University Press.

Omnipresence of the polyproline II helix in fibrous and globular proteins.

PubMed

Esipova, Natalia G; Tumanyan, Vladimir G

2017-02-01

Left-handed helical conformation of a polypeptide chain (PPII) is the third type of the protein backbone structure. This conformation universally exists in fibrous, globular proteins, and biologically active peptides. It has unique physical and chemical properties determining a wide range of biological functions, from the protein folding to the tissue differentiation. New examples of the structure have been appearing in spite of difficulties in their detection and investigation. The annotation and prediction of the PPII was also a challenging task. Recently, many PPII motifs with new and/or unexpected functions are being accumulated in databases. In this review we describe the major structural and dynamic forms of PPII, the diversity of its functions, and the role in different biological processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

The material and biological characteristics of osteoinductive calcium phosphate ceramics

PubMed Central

Tang, Zhurong; Li, Xiangfeng; Tan, Yanfei

2018-01-01

Abstract The discovery of osteoinductivity of calcium phosphate (Ca-P) ceramics has set an enduring paradigm of conferring biological regenerative activity to materials with carefully designed structural characteristics. The unique phase composition and porous structural features of osteoinductive Ca-P ceramics allow it to interact with signaling molecules and extracellular matrices in the host system, creating a local environment conducive to new bone formation. Mounting evidence now indicate that the osteoinductive activity of Ca-P ceramics is linked to their physicochemical and three-dimensional structural properties. Inspired by this conceptual breakthrough, many laboratories have shown that other materials can be also enticed to join the rank of tissue-inducing biomaterials, and besides the bones, other tissues such as cartilage, nerves and blood vessels were also regenerated with the assistance of biomaterials. Here, we give a brief historical recount about the discovery of the osteoinductivity of Ca-P ceramics, summarize the underlying material factors and biological characteristics, and discuss the mechanism of osteoinduction concerning protein adsorption, and the interaction with different types of cells, and the involvement of the vascular and immune systems. PMID:29423267

Biological activity of aldose reductase and lipophilicity of pyrrolyl-acetic acid derivatives

NASA Astrophysics Data System (ADS)

Kumari, A.; Kumari, R.; Kumar, R.; Gupta, M.

2011-12-01

Quantitative Structure-Activity Relationship modeling is a powerful approach for correlating an organic compound to its lipophilicity. In this paper QSAR models are established for estimation of correlation of the lipophilicity of a series of pyrrolyl-acetic acid derivatives, inhibitors of the aldose reductase enzyme, in the n-octanol-water system with biological activity of aldose reductase. Lipophilicity, expressed by the logarithm of n-octnol-water partition coefficient log P and biological activity of aldose reductase inhibitory activity by log it. Result obtained by QSAR modeling of compound series reveal a definite trend in biological activity and a further improvement in quantitative relationships are established if, beside log P, Hammett electronic constant σ and connectivity index chi-3 (3 χ) term included in the regression equation. The tri-parametric model with log P, 3 χ and σ as correlating parameters have been found to be the best which gives a variance of 87% ( R 2 = 0.8743). A compound has been found to be serious outlier and when the same has been excluded the model explains about 94% variance of the data set ( R 2 = 0.9447). The topological index (3 χ) has been found to be a good parameter for modeling the biological activity.

Isolation and biological evaluation of jatrophane diterpenoids from Euphorbia dendroides.

PubMed

Aljancić, Ivana S; Pesić, Milica; Milosavljević, Slobodan M; Todorović, Nina M; Jadranin, Milka; Milosavljević, Goran; Povrenović, Dragan; Banković, Jasna; Tanić, Nikola; Marković, Ivanka D; Ruzdijić, Sabera; Vajs, Vlatka E; Tesević, Vele V

2011-07-22

From the Montenegrin spurge Euphorbia dendroides, seven new diterpenoids [jatrophanes (1-6) and a tigliane (7)] were isolated and their structures elucidated by spectroscopic techniques. The biological activity of the new compounds was studied against four human cancer cell lines. The most effective jatrophane-type compound (2) and its structurally closely related derivative (1) were evaluated for their interactions with paclitaxel and doxorubicin using a multi-drug-resistant cancer cell line. Both compounds exerted a strong reversal potential resulting from inhibition of P-glycoprotein transport.

Towards noninvasive drug distribution in tissues: coherent Raman microspectroscopy of chiral molecules

NASA Astrophysics Data System (ADS)

Petrov, Georgi I.; Yakovlev, Vladislav V.

2017-02-01

Many biologically active molecules are chiral. Many drugs, which are currently in use, are supplied as an equimolar mixture of enantiomers. Although they have the same chemical structure, i.e. are not distinguishable by conventional Raman spectroscopy, most isomers of chiral drugs exhibit marked differences in biological activities such as pharmacology, toxicology, pharmacokinetics, metabolism, etc. In this report we introduced a new spectroscopic tool to extend nonlinear Raman spectroscopy to chiral substances.

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology.

PubMed

Fajkus, J; Simícková, M; Maláska, J

2002-04-29

The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

"Pruning of biomolecules and natural products (PBNP)": an innovative paradigm in drug discovery.

PubMed

Bathula, Surendar Reddy; Akondi, Srirama Murthy; Mainkar, Prathama S; Chandrasekhar, Srivari

2015-06-21

The source or inspiration of many marketed drugs can be traced back to natural product research. However, the chemical structure of natural products covers a wide spectrum from very simple to complex. With more complex structures it is often desirable to simplify the molecule whilst retaining the desired biological activity. This approach seeks to identify the structural unit or pharmacophore responsible for the desired activity. Such pharmacophores have been the start point for a wide range of lead generation and optimisation programmes using techniques such as Biology Oriented Synthesis, Diversity Oriented Synthesis, Diverted Total Synthesis, and Fragment Based Drug Discovery. This review discusses the literature precedence of simplification strategies in four areas of natural product research: proteins, polysaccharides, nucleic acids, and compounds isolated from natural product extracts, and their impact on identifying therapeutic products.

Spacer conformation in biologically active molecules. Part 2. Structure and conformation of 4-[2-(diphenylmethylamino)ethyl]-1-(2-methoxyphenyl) piperazine and its diphenylmethoxy analog—potential 5-HT 1A receptor ligands

NASA Astrophysics Data System (ADS)

Karolak-Wojciechowska, J.; Fruziński, A.; Czylkowski, R.; Paluchowska, M. H.; Mokrosz, M. J.

2003-09-01

As a part of studies on biologically active molecule structures with aliphatic linking chain, the structures of 4-[2-diphenylmethylamino)ethyl]-1-(2-methoxyphenyl)piperazine dihydrochloride ( 1) and 4-[2-diphenylmethoxy)ethyl]-1-(2-methoxyphenyl)piperazine fumarate ( 2) have been reported. In both compounds, four atomic non-all-carbons linking chains (N)C-C-X-C are present. The conformation of that linking spacer depends on the nature of the X-atom. The preferred conformation for chain with XNH has been found to be fully extended while for that with XO—the bend one. It was confirmed by conformational calculations (strain energy distribution and random search) and crystallographic data, including statistics from CCDC.

TIPdb-3D: the three-dimensional structure database of phytochemicals from Taiwan indigenous plants

PubMed Central

Tung, Chun-Wei; Lin, Ying-Chi; Chang, Hsun-Shuo; Wang, Chia-Chi; Chen, Ih-Sheng; Jheng, Jhao-Liang; Li, Jih-Heng

2014-01-01

The rich indigenous and endemic plants in Taiwan serve as a resourceful bank for biologically active phytochemicals. Based on our TIPdb database curating bioactive phytochemicals from Taiwan indigenous plants, this study presents a three-dimensional (3D) chemical structure database named TIPdb-3D to support the discovery of novel pharmacologically active compounds. The Merck Molecular Force Field (MMFF94) was used to generate 3D structures of phytochemicals in TIPdb. The 3D structures could facilitate the analysis of 3D quantitative structure–activity relationship, the exploration of chemical space and the identification of potential pharmacologically active compounds using protein–ligand docking. Database URL: http://cwtung.kmu.edu.tw/tipdb. PMID:24930145

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar

PubMed Central

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-01-01

Objective To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Methods Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Results Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) µg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) µg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. Conclusions The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. PMID:24075342

Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar.

PubMed

Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

2013-10-01

To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) μg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) μg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Structure-function similarities between a plant receptor-like kinase and the human interleukin-1 receptor-associated kinase-4.

PubMed

Klaus-Heisen, Dörte; Nurisso, Alessandra; Pietraszewska-Bogiel, Anna; Mbengue, Malick; Camut, Sylvie; Timmers, Ton; Pichereaux, Carole; Rossignol, Michel; Gadella, Theodorus W J; Imberty, Anne; Lefebvre, Benoit; Cullimore, Julie V

2011-04-01

Phylogenetic analysis has previously shown that plant receptor-like kinases (RLKs) are monophyletic with respect to the kinase domain and share an evolutionary origin with the animal interleukin-1 receptor-associated kinase/Pelle-soluble kinases. The lysin motif domain-containing receptor-like kinase-3 (LYK3) of the legume Medicago truncatula shows 33% amino acid sequence identity with human IRAK-4 over the kinase domain. Using the structure of this animal kinase as a template, homology modeling revealed that the plant RLK contains structural features particular to this group of kinases, including the tyrosine gatekeeper and the N-terminal extension α-helix B. Functional analysis revealed the importance of these conserved features for kinase activity and suggests that kinase activity is essential for the biological role of LYK3 in the establishment of the root nodule nitrogen-fixing symbiosis with rhizobia bacteria. The kinase domain of LYK3 has dual serine/threonine and tyrosine specificity, and mass spectrometry analysis identified seven serine, eight threonine, and one tyrosine residue as autophosphorylation sites in vitro. Three activation loop serine/threonine residues are required for biological activity, and molecular dynamics simulations suggest that Thr-475 is the prototypical phosphorylated residue that interacts with the conserved arginine in the catalytic loop, whereas Ser-471 and Thr-472 may be secondary sites. A threonine in the juxtamembrane region and two threonines in the C-terminal lobe of the kinase domain are important for biological but not kinase activity. We present evidence that the structure-function similarities that we have identified between LYK3 and IRAK-4 may be more widely applicable to plant RLKs in general.

Discovery of a Manduca sexta Allatotropin Antagonist from a Manduca sexta Allatotropin Receptor Homology Model.

PubMed

Kai, Zhen-Peng; Zhu, Jing-Jing; Deng, Xi-Le; Yang, Xin-Ling; Chen, Shan-Shan

2018-04-03

Insect G protein coupled receptors (GPCRs) have important roles in modulating biology, physiology and behavior. They have been identified as candidate targets for next-generation insecticides, yet these targets have been relatively poorly exploited for insect control. In this study, we present a pipeline of novel Manduca sexta allatotropin (Manse-AT) antagonist discovery with homology modeling, docking, molecular dynamics simulation and structure-activity relationship. A series of truncated and alanine-replacement analogs of Manse-AT were assayed for the stimulation of juvenile hormone biosynthesis. The minimum sequence required to retain potent biological activity is the C -terminal amidated octapeptide Manse-AT (6-13). We identified three residues essential for bioactivity (Thr⁴, Arg6 and Phe⁸) by assaying alanine-replacement analogs of Manse-AT (6-13). Alanine replacement of other residues resulted in reduced potency but bioactivity was retained. The 3D structure of the receptor (Manse-ATR) was built and the binding pocket was identified. The binding affinities of all the analogs were estimated by calculating the free energy of binding. The calculated binding affinities corresponded to the biological activities of the analogs, which supporting our localization of the binding pocket. Then, based on the docking and molecular dynamics studies of Manse-AT (10-13), we described it can act as a potent Manse-AT antagonist. The antagonistic effect on JH biosynthesis of Manse-AT (10-13) validated our hypothesis. The IC 50 value of antagonist Manse-AT (10-13) is 0.9 nM. The structure-activity relationship of antagonist Manse-AT (10-13) was also studied for the further purpose of investigating theoretically the structure factors influencing activity. These data will be useful for the design of new Manse-AT agonist and antagonist as potential pest control agents.

In Silico Docking of Small-Molecule Inhibitors to the Escherichia coli Type III Secretion System EscN ATPase

DTIC Science & Technology

2014-07-01

coordinates of the EscN protein (Zarivach et al., 2007) were downloaded in pdb file format from the Research Collaboratory for Structural Biology...catalytic activity. Two structurally related compounds were observed to adopt extended conformations in the active-site cleft and essentially...adopt a very compact conformation that occupied only one side of the cleft. Our goal was to determine the three-dimensional structures of the

Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

PubMed

Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

2018-05-17

In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses

PubMed Central

Brosey, Chris A.; Ahmed, Zamal; Lees-Miller, Susan P.; Tainer, John A.

2017-01-01

DNA damage outcomes depend upon the efficiency and fidelity of DNA damage responses (DDRs) for different cells and damage. As such, DDRs represent tightly regulated prototypical systems for linking nanoscale biomolecular structure and assembly to the biology of genomic regulation and cell signaling. However, the dynamic and multifunctional nature of DDR assemblies can render elusive the correlation between the structures of DDR factors and specific biological disruptions to the DDR when these structures are altered. In this chapter, we discuss concepts and strategies for combining structural, biophysical, and imaging techniques to investigate DDR recognition and regulation, and thus bridge sequence-level structural biochemistry to quantitative biological outcomes visualized in cells. We focus on representative DDR responses from PARP/PARG/AIF damage signaling in DNA single-strand break repair and nonhomologous end joining complexes in double-strand break repair. Methods with exemplary experimental results are considered with a focus on strategies for probing flexibility, conformational changes, and assembly processes that shape a predictive understanding of DDR mechanisms in a cellular context. Integration of structural and imaging measurements promises to provide foundational knowledge to rationally control and optimize DNA damage outcomes for synthetic lethality and for immune activation with resulting insights for biology and cancer interventions. PMID:28668129

Quantitative structure-antifungal activity relationships of some benzohydrazides against Botrytis cinerea.

PubMed

Reino, José L; Saiz-Urra, Liane; Hernandez-Galan, Rosario; Aran, Vicente J; Hitchcock, Peter B; Hanson, James R; Gonzalez, Maykel Perez; Collado, Isidro G

2007-06-27

Fourteen benzohydrazides have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The best antifungal activity was observed for the N',N'-dibenzylbenzohydrazides 3b-d and for the N-aminoisoindoline-derived benzohydrazide 5. A quantitative structure-activity relationship (QSAR) study has been developed using a topological substructural molecular design (TOPS-MODE) approach to interpret the antifungal activity of these synthetic compounds. The model described 98.3% of the experimental variance, with a standard deviation of 4.02. The influence of an ortho substituent on the conformation of the benzohydrazides was investigated by X-ray crystallography and supported by QSAR study. Several aspects of the structure-activity relationships are discussed in terms of the contribution of different bonds to the antifungal activity, thereby making the relationships between structure and biological activity more transparent.

Biological and Chemical Aspects of Natural Biflavonoids from Plants: A Brief Review.

PubMed

Gontijo, Vanessa Silva; Dos Santos, Marcelo Henrique; Viegas, Claudio

2017-01-01

Biflavonoids belong to a subclass of the plant flavonoids family and are limited to several species in the plant kingdom. In the literature, biflavonoids are extensively reported for their pharmacological properties including anti-inflammatory, antioxidant, inhibitory activity against phospholipase A2 (PLA2) and antiprotozoal activity. These activities have been discovered from the small number of biflavonoid structures that have been investigated, although the natural biflavonoids library is likely to be large. In addition, many medicinal properties and traditional use of plants are attributed to the presence of bioflavonoids among their secondary metabolites. Structurally, biflavonoids are polyphenol compounds comprising of two identical or non-identical flavonflavonoid units joined in a symmetrical or unsymmetrical manner through an alkyl or an alkoxy-based linker of varying length. Due to their chemical and biological importance, several bioprospective phytochemical studies and chemical approaches using coupling and molecular rearrangement strategies have been developed to identify and synthesize new bioactive biflavonoids. In this brief review, we present some basic structural aspects for classification and nomenclature of bioflavonoids and a compilation of the literature data published in the last 7 years, concerning the discovery of new natural biflavonoids of plant origin and their pharmacological and biological properties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of capping agents: Structural, optical and biological properties of ZnO nanoparticles

NASA Astrophysics Data System (ADS)

Javed, Rabia; Usman, Muhammad; Tabassum, Saira; Zia, Muhammad

2016-11-01

Different biological activities of capped and uncapped ZnO nanoparticles were investigated, and the effects of potential capping agents on these biological activities were studied. ZnO nanoparticles were synthesized and capped by polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) using a simple chemical method of co-precipitation. Characterization by X-ray diffraction (XRD), Fourier transform Infrared spectroscopy (FTIR) and UV-vis spectroscopy confirmed the crystallinity, size, functional group, and band gap of synthesized nanoparticles. Reduction in size occurred from 34 nm to 26 nm due to surfactant. Results of all biological activities indicated significantly higher values in capped as compared to uncapped nanoparticles. Antibacterial activity against Staphylococcus aureus (ATCC 6538), Bacillus subtilis (ATCC 6633), Escherichia coli (ATCC15224), and Acetobacter was obtained. This activity was more prominent against Gram-positive bacteria, and ZnO-PVP nanoparticles elucidated highest antibacterial activity (zone of inhibition 17 mm) against Gram-positive, Bacillus subtilis species. Antioxidant activities including total flavonoid content, total phenolic content, total antioxidant capacity, total reducing power and %age inhibition of DPPH, and antidiabetic activity against α-amylase enzyme found to be exhibited highest by ZnO-PEG nanoparticles.

Short-term C mineralization (aka the flush of CO2) as an indicator of soil biological health

USDA-ARS?s Scientific Manuscript database

Soil biological activity is a key component of soil health assessments, as it (a) indicates soil nutrient cycling capacity from various organic matter sources to inorganic availability, (b) relates to soil structural conditions, (c) informs about the potential to harbor biodiversity in soil, and (d)...

Novel Natural Products from Extremophilic Fungi.

PubMed

Zhang, Xuan; Li, Shou-Jie; Li, Jin-Jie; Liang, Zi-Zhen; Zhao, Chang-Qi

2018-06-04

Extremophilic fungi have been found to develop unique defences to survive extremes of pressure, temperature, salinity, desiccation, and pH, leading to the biosynthesis of novel natural products with diverse biological activities. The present review focuses on new extremophilic fungal natural products published from 2005 to 2017, highlighting the chemical structures and their biological potential.

Early integration of the individual student in academic activities: a novel classroom concept for graduate education in molecular biophysics and structural biology

PubMed Central

2014-01-01

Background A key challenge in interdisciplinary research is choosing the best approach from a large number of techniques derived from different disciplines and their interfaces. Results To address this challenge in the area of Biophysics and Structural Biology, we have designed a graduate level course to teach students insightful use of experimental biophysical approaches in relationship to addressing biological questions related to biomolecular interactions and dynamics. A weekly seminar and data and literature club are used to compliment the training in class. The course contains wet-laboratory experimental demonstration and real-data analysis as well as lectures, grant proposal preparation and assessment, and student presentation components. Active student participation is mandatory in all aspects of the class. Students prepare materials for the class receiving individual and iterative feedback from course directors and local experts generating high quality classroom presentations. Conclusions The ultimate goal of the course is to teach students the skills needed to weigh different experimental approaches against each other in addressing a specific biological question by thinking and executing academic tasks like faculty. PMID:25132964

Early integration of the individual student in academic activities: a novel classroom concept for graduate education in molecular biophysics and structural biology.

PubMed

Leuba, Sanford H; Carney, Sean M; Dahlburg, Elizabeth M; Eells, Rebecca J; Ghodke, Harshad; Yanamala, Naveena; Schauer, Grant; Klein-Seetharaman, Judith

2014-01-01

A key challenge in interdisciplinary research is choosing the best approach from a large number of techniques derived from different disciplines and their interfaces. To address this challenge in the area of Biophysics and Structural Biology, we have designed a graduate level course to teach students insightful use of experimental biophysical approaches in relationship to addressing biological questions related to biomolecular interactions and dynamics. A weekly seminar and data and literature club are used to compliment the training in class. The course contains wet-laboratory experimental demonstration and real-data analysis as well as lectures, grant proposal preparation and assessment, and student presentation components. Active student participation is mandatory in all aspects of the class. Students prepare materials for the class receiving individual and iterative feedback from course directors and local experts generating high quality classroom presentations. The ultimate goal of the course is to teach students the skills needed to weigh different experimental approaches against each other in addressing a specific biological question by thinking and executing academic tasks like faculty.

Isolation, structural elucidation and immunomodulatory activity of fructans from aged garlic extract.

PubMed

Chandrashekar, Puthanapura M; Prashanth, Keelara V Harish; Venkatesh, Yeldur P

2011-02-01

Traditionally, garlic (Allium sativum) is known to be a significant immune booster. Aged garlic extract (AGE) possesses superior immunomodulatory effects than raw garlic; these effects are attributed to the transformed organosulfur compounds. AGE is also known to contain fructans; the amount of fructans in AGE represents a small fraction (0.22%) of the total fructans in raw garlic. In order to evaluate the biological activity of fructans present in AGE, both high molecular weight (>3.5 kDa; HF) and low molecular weight (<3 kDa; LF) fructans were isolated. The structures of purified HF and LF from AGE determined by (1)H NMR and (13)C NMR spectroscopy revealed that both have (2→1) β-D-fructofuranosyl bonds linked to a terminal glucose at the non-reducing end and β-D-fructofuranosyl branching on its backbone. Biological activity of fructans was assessed by immunostimulatory activity using murine lymphocytes and peritoneal exudate cells (source of macrophages). Both HF and LF displayed mitogenic activity and activation of macrophages including phagocytosis. These activities were comparable to that of known polysaccharide immunomodulators such as zymosan and mannan. This study clearly demonstrates that garlic fructans also contribute to the immunomodulatory properties of AGE, and is the first such study on the biological effects of garlic fructans. Copyright © 2010 Elsevier Ltd. All rights reserved.

Biophysical principles of regulatory action of low-intensity laser irradiation

NASA Astrophysics Data System (ADS)

Mostovnikov, Vasili A.; Mostovnikova, Galina R.; Plavski, Vitali Y.; Plavskaja, Ljudmila G.

1996-01-01

The investigations carried out in our group on biological systems of various organization level (enzyme molecules in solution, human and animal cell cultures), allowed us to conclude, that the light-induced changes of spatial structure of cells components form the basis of biological activity (and as a consequence therapeutic effect) of various wavelength low-intensity laser emission. Photophysical mechanism of these changes lies in the reorientation of highregulated anisotropic parts (domains) with the liquid-crystalline type of ordering of the cell components due to the interaction between the electric field and the light induced integral electric dipole of the domain. The mechanism of such reorientation is well established in physics of liquid crystals of nematic type and is known as light induced analogue of Frederix's effect. The following results enable us to draw the conclusion about the determining role of the orientations effects on the biological activity mechanism of low-intensity laser radiation: (1) the possibility of reversible modification of spatial structure and enzyme molecules functional activity under the influence of laser radiation outside the band of their own or admixture absorption; (2) the dependence of biological effect of laser radiation on the functional activity of cells vs. polarization degree of the light with the maximum photobiological effects observed for linear-polarized radiation; (3) the equivalence of a static magnetic field and low-intensity laser radiation in action on functional activity of the cells and the lowering of the laser field intensity for the achieving the definite changes of the cell functional activity in the presence of static magnetic field.

Ancient cellular structures and modern humans: change of survival strategies before prolonged low solar activity period

NASA Astrophysics Data System (ADS)

Ragulskaya, Mariya; Rudenchik, Evgeniy; Gromozova, Elena; Voychuk, Sergei; Kachur, Tatiana

The study of biotropic effects of modern space weather carries the information about the rhythms and features of adaptation of early biological systems to the outer space influence. The influence of cosmic rays, ultraviolet waves and geomagnetic field on early life has its signs in modern biosphere processes. These phenomena could be experimentally studied on present-day biological objects. Particularly inorganic polyphosphates, so-called "fossil molecules", attracts special attention as the most ancient molecules which arose in inanimate nature and have been accompanying biological objects at all stages of evolution. Polyphosphates-containing graves of yeast's cells of Saccharomyces cerevisiae strain Y-517, , from the Ukrainian Collection of Microorganisms was studied by daily measurements during 2000-2013 years. The IZMIRAN daily data base of physiological parameters dynamics during 2000-2013 years were analyzed simultaneously (25 people). The analysis showed significant simultaneous changes of the statistical parameters of the studied biological systems in 2004 -2006. The similarity of simultaneous changes of adaptation strategies of human organism and the cell structures of Saccharomyces cerevisiae during the 23-24 cycles of solar activity are discussed. This phenomenon could be due to a replacement of bio-effective parameters of space weather during the change from 23rd to 24th solar activity cycle and nonstandard geophysical peculiarities of the 24th solar activity cycle. It could be suggested that the observed similarity arose as the optimization of evolution selection of the living systems in expectation of probable prolonged period of low solar activity (4-6 cycles of solar activity).

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

PubMed

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Low Resolution Solution Structure of HAMLET and the Importance of Its Alpha-Domains in Tumoricidal Activity

PubMed Central

Ho CS, James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells. PMID:23300861

Chemical composition and biological activity of ripe pumpkin fruits (Cucurbita pepo L.) cultivated in Egyptian habitats.

PubMed

Badr, Sherif E A; Shaaban, Mohamed; Elkholy, Yehya M; Helal, Maher H; Hamza, Akila S; Masoud, Mohamed S; El Safty, Mounir M

2011-09-01

The chemical composition and biological activity of three parts (rind, flesh and seeds) of pumpkin fruits (Cucurbita pepo L.) cultivated in Egypt were studied. Chemical analysis of fibre, protein, β-carotene, carbohydrates, minerals and fatty acids present in the rind, flesh, seeds and defatted seeds meal was conducted. Chemical, GC-MS and biological assays of organic extracts of the main fruit parts, rind and flesh established their unique constituents. Chromatographic purification of the extracts afforded triglyceride fatty acid mixture (1), tetrahydro-thiophene (2), linoleic acid (3), calotropoleanly ester (4), cholesterol (5) and 13(18)-oleanen-3-ol (6). GC-MS analysis of the extract's unpolar fraction revealed the existence of dodecane and tetradecane. Structures of the isolated compounds (1-6) were confirmed by NMR and EI-MS spectrometry. Antimicrobial, antiviral and antitumour activities of the fruit parts were discussed. The promising combined extract of rind and flesh was biologically studied for microbial and cytotoxic activities in comparison with the whole isolated components.

Discovery of chitin in skeletons of non-verongiid Red Sea demosponges.

PubMed

Ehrlich, Hermann; Shaala, Lamiaa A; Youssef, Diaa T A; Żółtowska-Aksamitowska, Sonia; Tsurkan, Mikhail; Galli, Roberta; Meissner, Heike; Wysokowski, Marcin; Petrenko, Iaroslav; Tabachnick, Konstantin R; Ivanenko, Viatcheslav N; Bechmann, Nicole; Joseph, Yvonne; Jesionowski, Teofil

2018-01-01

Marine demosponges (Porifera: Demospongiae) are recognized as first metazoans which have developed over millions of years of evolution effective survival strategies based on unique metabolic pathways to produce both biologically active secondary metabolites and biopolymer-based stiff skeletons with 3D architecture. Up to date, among marine demosponges, only representatives of the Verongiida order have been known to synthetize biologically active substances as well as skeletons made of structural polysaccharide chitin. This work, to our knowledge, demonstrates for the first time that chitin is an important structural component within skeletons of non-verongiid demosponges Acarnus wolffgangi and Echinoclathria gibbosa collected in the Red Sea. Calcofluor white staining, FTIR and Raman analysis, ESI-MS, SEM, and fluorescence microscopy as well as a chitinase digestion assay were applied in order to confirm, with strong evidence, the finding of α-chitin in the skeleton of both species. We suggest that, the finding of chitin within these representatives of Poecilosclerida order is a promising step in the evaluation of these sponges as novel renewable sources for both biologically active metabolites and chitin, which are of prospective application for pharmacology and biomedicine.

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs

PubMed Central

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-01-01

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent. PMID:19725977

Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs.

PubMed

Padhye, Subhash; Ahmad, Aamir; Oswal, Nikhil; Sarkar, Fazlul H

2009-09-02

Garcinol, harvested from Garcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.

Occurrence, biological activity and metabolism of 6-shogaol.

PubMed

Kou, Xingran; Wang, Xiaoqi; Ji, Ruya; Liu, Lang; Qiao, Yening; Lou, Zaixiang; Ma, Chaoyang; Li, Shiming; Wang, Hongxin; Ho, Chi-Tang

2018-03-01

As one of the main bioactive compounds of dried ginger, 6-shogaol has been widely used to alleviate many ailments. It is also a major pungent flavor component, and its precursor prior to dehydration is 6-gingerol, which is reported to be responsible for the pungent flavor and biological activity of fresh ginger. Structurally, gingerols including 6-gingerol have a β-hydroxyl ketone moiety and is liable to dehydrate to generate an α,β-unsaturated ketone under heat and/or acidic conditions. The conjugation of the α,β-unsaturated ketone skeleton in the chemical structure of 6-shogaol explicates its higher potency and efficacy than 6-gingerol in terms of antioxidant, anti-inflammatory, anticancer, antiemetic and other bioactivities. Research on the health benefits of 6-shogaol has been conducted and results have been reported recently; however, scientific data are scattered due to a lack of systematic collection. In addition, action mechanisms of the preventive and/or therapeutic actions of 6-shogaol remain obscurely non-collective. Herein, we review the preparations, biological activity and mechanisms, and metabolism of 6-shogaol as well as the properties of 6-shogaol metabolites.

Biomedical and Catalytic Opportunities of Virus-Like Particles in Nanotechnology.

PubMed

Schwarz, B; Uchida, M; Douglas, T

2017-01-01

Within biology, molecules are arranged in hierarchical structures that coordinate and control the many processes that allow for complex organisms to exist. Proteins and other functional macromolecules are often studied outside their natural nanostructural context because it remains difficult to create controlled arrangements of proteins at this size scale. Viruses are elegantly simple nanosystems that exist at the interface of living organisms and nonliving biological machines. Studied and viewed primarily as pathogens to be combatted, viruses have emerged as models of structural efficiency at the nanoscale and have spurred the development of biomimetic nanoparticle systems. Virus-like particles (VLPs) are noninfectious protein cages derived from viruses or other cage-forming systems. VLPs provide incredibly regular scaffolds for building at the nanoscale. Composed of self-assembling protein subunits, VLPs provide both a model for studying materials' assembly at the nanoscale and useful building blocks for materials design. The robustness and degree of understanding of many VLP structures allow for the ready use of these systems as versatile nanoparticle platforms for the conjugation of active molecules or as scaffolds for the structural organization of chemical processes. Lastly the prevalence of viruses in all domains of life has led to unique activities of VLPs in biological systems most notably the immune system. Here we discuss recent efforts to apply VLPs in a wide variety of applications with the aim of highlighting how the common structural elements of VLPs have led to their emergence as paradigms for the understanding and design of biological nanomaterials. © 2017 Elsevier Inc. All rights reserved.

Physico-chemical properties and cytotoxic effects of sugar-based surfactants: Impact of structural variations.

PubMed

Lu, Biao; Vayssade, Muriel; Miao, Yong; Chagnault, Vincent; Grand, Eric; Wadouachi, Anne; Postel, Denis; Drelich, Audrey; Egles, Christophe; Pezron, Isabelle

2016-09-01

Surfactants derived from the biorefinery process can present interesting surface-active properties, low cytotoxicity, high biocompatibility and biodegradability. They are therefore considered as potential sustainable substitutes to currently used petroleum-based surfactants. To better understand and anticipate their performances, structure-property relationships need to be carefully investigated. For this reason, we applied a multidisciplinary approach to systematically explore the effect of subtle structural variations on both physico-chemical properties and biological effects. Four sugar-based surfactants, each with an eight carbon alkyl chain bound to a glucose or maltose head group by an amide linkage, were synthesized and evaluated together along with two commercially available standard surfactants. Physico-chemical properties including solubility, Krafft point, surface-tension lowering and critical micellar concentration (CMC) in water and biological medium were explored. Cytotoxicity evaluation by measuring proliferation index and metabolic activity against dermal fibroblasts showed that all surfactants studied may induce cell death at low concentrations (below their CMC). Results revealed significant differences in both physico-chemical properties and cytotoxic effects depending on molecule structural features, such as the position of the linkage on the sugar head-group, or the orientation of the amide linkage. Furthermore, the cytotoxic response increased with the reduction of surfactant CMC. This study underscores the relevance of a methodical and multidisciplinary approach that enables the consideration of surfactant solution properties when applied to biological materials. Overall, our results will contribute to a better understanding of the concomitant impact of surfactant structure at physico-chemical and biological levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Disulfide Bond Formation and Activation of Escherichia coli β-Galactosidase under Oxidizing Conditions

PubMed Central

Seras-Franzoso, Joaquin; Affentranger, Roman; Ferrer-Navarro, Mario; Daura, Xavier; Villaverde, Antonio

2012-01-01

Escherichia coli β-galactosidase is probably the most widely used reporter enzyme in molecular biology, cell biology, and biotechnology because of the easy detection of its activity. Its large size and tetrameric structure make this bacterial protein an interesting model for crystallographic studies and atomic mapping. In the present study, we investigate a version of Escherichia coli β-galactosidase produced under oxidizing conditions, in the cytoplasm of an Origami strain. Our data prove the activation of this microbial enzyme under oxidizing conditions and clearly show the occurrence of a disulfide bond in the β-galactosidase structure. Additionally, the formation of this disulfide bond is supported by the analysis of a homology model of the protein that indicates that two cysteines located in the vicinity of the catalytic center are sufficiently close for disulfide bond formation. PMID:22286993

Chemical and bioactive diversities of the genus Chaetomium secondary metabolites.

PubMed

Zhang, Q; Li, H-Q; Zong, S-C; Gao, J-M; Zhang, A-L

2012-02-01

The genus Chaetomium fungi are considered to be a rich source of novel and bioactive secondary metabolites of great importance. Up till now, a variety of more than 200 secondary metabolites belonging to diverse structural types of chaetoglobosins, epipolythiodioxopiperazines, azaphilones, xanthones, anthraquinones, chromones, depsidones, terpenoids, and steroids have been discovered. Most of these fungal metabolites exhibited antitumor, cytotoxic, antimalarial, enzyme inhibitory, antibiotic, and other activities. This review covers the extraction, structure elucidation, structural diversity, and biological activities of natural products isolated from about 30 fungi associated with marine- and terrestrial- origins, and highlights some bioactive compounds as well as their mechanisms of action and structure-activity relationships.

New Peptides Isolated from Marine Cyanobacteria, an Overview over the Past Decade.

PubMed

Mi, Yue; Zhang, Jinrong; He, Shan; Yan, Xiaojun

2017-05-05

Marine cyanobacteria are significant sources of structurally diverse marine natural products with broad biological activities. In the past 10 years, excellent progress has been made in the discovery of marine cyanobacteria-derived peptides with diverse chemical structures. Most of these peptides exhibit strong pharmacological activities, such as neurotoxicity and cytotoxicity. In the present review, we summarized peptides isolated from marine cyanobacteria since 2007.

Sodium and Potassium Ions in Proteins and Enzyme Catalysis.

PubMed

Vašák, Milan; Schnabl, Joachim

2016-01-01

The group I alkali metal ions Na(+) and K(+) are ubiquitous components of biological fluids that surround biological macromolecules. They play important roles other than being nonspecific ionic buffering agents or mediators of solute exchange and transport. Molecular evolution and regulated high intracellular and extracellular M(+) concentrations led to incorporation of selective Na(+) and K(+) binding sites into enzymes to stabilize catalytic intermediates or to provide optimal positioning of substrates. The mechanism of M(+) activation, as derived from kinetic studies along with structural analysis, has led to the classification of cofactor-like (type I) or allosteric effector (type II) activated enzymes. In the type I mechanism substrate anchoring to the enzyme active site is mediated by M(+), often acting in tandem with a divalent cation like Mg(2+), Mn(2+) or Zn(2+). In the allosteric type II mechanism, M(+) binding enhances enzyme activity through conformational transitions triggered upon binding to a distant site. In this chapter, following the discussion of the coordination chemistry of Na(+) and K(+) ions and the structural features responsible for the metal binding site selectivity in M(+)-activated enzymes, well-defined examples of M(+)-activated enzymes are used to illustrate the structural basis for type I and type II activation by Na(+) and K(+).

Phytochemical and biological studies of Atriplex inflata f. Muell.: isolation of secondary bioactive metabolites.

PubMed

Ben Nejma, Aymen; Znati, Mansour; Nguir, Asma; Daich, Adam; Othman, Mohamed; Lawson, Ata Martin; Ben Jannet, Hichem

2017-08-01

This work describes the phytochemical and biological investigation of the Tunisian Atriplex inflata F. Muell (Chenopodiaceae). Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D NMR and 2D NMR, ESI-HRMS and comparison with available literature data. The isolates were evaluated for their antioxidant activity by the DPPH • , ABTS +• , Fe 3+ and catalase assays and also for their antibacterial and anticholinesterase activity. The chemical study of Atriplex inflata F. Muell led to the isolation of two fatty acids (9E)-methyl-8,11,12-trihydroxyoctadec-9-enoate 1 and (9E)-8,11,12-trihydroxyoctadecenoic acid 2 together with (Z)-litchiol B 3 and 20-hydroxyecdysone 4. Three of which are reported here for the first time in Atriplex genus. Based on the biosynthesis of hydroxylated arachidonic acid and derivatives, a plausible biogenesis pathway of the two fatty acids (1 and 2) was proposed. (Z)-litchiol B (3) was found to be the most active against Staphylococcus aureus. According to the literature, this is the first time that compounds 1, 2 and 3 were tested for their eventual biological activity. In the results of the present work, we have proposed the biogenesis pathway of unsaturated fatty acid and described the structure-activity relationship. © 2017 Royal Pharmaceutical Society.

Structural and functional characterization of recombinant napin-like protein of Momordica charantia expressed in methylotrophic yeast Pichia pastoris.

PubMed

Yadav, Shailesh Kumar R; Sahu, Tejram; Dixit, Aparna

2016-08-01

Napin and napin-like proteins belong to the 2S albumin seed storage family of proteins and have been shown to display a variety of biological activities. However, due to a high degree of polymorphism, purification of a single napin or napin-like protein exhibiting biological activity is extremely difficult. In the present study, we have produced the napin-like protein of Momordica charantia using the methylotrophic Pichia pastoris expression system. The recombinant napin-like protein (rMcnapin) secreted in the extracellular culture supernatant was enriched by ammonium sulfate precipitation, and purified using size exclusion chromatography at a yield of ∼290 mg/L of culture. Secondary structure analysis of the purified rMcnapin revealed it to be predominantly α-helical with minimal β strand content. CD spectroscopic and fluorescence spectroscopic analyses revealed the rMcnapin to be stable at a wide range of temperatures and pH. The rMcnapin exhibited antifungal activity against Trichoderma viride with an IC50 of ∼3.7 μg/ml and trypsin inhibitor activity with an IC50 of 4.2 μM. Thus, large amounts of homogenous preparations of the biologically active rMcnapin could be obtained at shake flask level, which is otherwise difficult from its natural source.

Influence of powdered activated carbon addition on water quality, sludge properties, and microbial characteristics in the biological treatment of commingled industrial wastewater.

PubMed

Hu, Qing-Yuan; Li, Meng; Wang, Can; Ji, Min

2015-09-15

A powdered activated carbon-activated sludge (PAC-AS) system, a traditional activated sludge (AS) system, and a powdered activated carbon (PAC) system were operated to examine the insights into the influence of PAC addition on biological treatment. The average COD removal efficiencies of the PAC-AS system (39%) were nearly double that of the AS system (20%). Compared with the average efficiencies of the PAC system (7%), COD removal by biodegradation in the PAC-AS system was remarkably higher than that in the AS system. The analysis of the influence of PAC on water quality and sludge properties showed that PAC facilitated the removal of hydrophobic matter and metabolic acidic products, and also enhanced the biomass accumulation, sludge settleability, and specific oxygen uptake rate inside the biological system. The microbial community structures in the PAC-AS and AS systems were monitored. The results showed that the average well color development in the PAC-AS system was higher than that in the AS system. The utilization of various substrates by microorganisms in the two systems did not differ. The dissimilarity index was far less than one; thus, showing that the microbial community structures of the two systems were the same. Copyright © 2015 Elsevier B.V. All rights reserved.

Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.

PubMed

Mor, Marco; Rivara, Silvia; Lodola, Alessio; Lorenzi, Simone; Bordi, Fabrizio; Plazzi, Pier Vincenzo; Spadoni, Gilberto; Bedini, Annalida; Duranti, Andrea; Tontini, Andrea; Tarzia, Giorgio

2005-11-01

Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.

Synthesis, crystal structure, cytotoxic, antileishmanial activities and docking studies on N,N‧-(ethane-1,2-diyl)bis(3-methylbenzamide)

NASA Astrophysics Data System (ADS)

Aziz, Hamid; Saeed, Aamer; Jabeen, Farukh; Simpson, Jim; Munawar, Amna; Qasim, Muhammad

2018-03-01

Amide derivatives have gained considerable attention because of their extensive range of biological activities and pharmaceutical applications. The current paper presents the synthesis of N, N‧-(ethane-1,2-diyl) bis (3-methylbenzamide), (I), its molecular and crystal structure and an evaluation of its likely biological activity, including cytotoxicity (LD50 = 37.21 μg/ml) and antileishmanial activity (IC50 = 5.77 μg/ml). Moreover, a docking simulation was used to determine the possible interaction sites of the compound (I) with TryR, an enzyme involved in the redox metabolism of the leishmania parasite. Docking computations demonstrate that the compound established prominent binding interactions with the key residues of the TryR and possess the potential to effectively inhibit the catalytic activities of the enzyme. Thus the results suggest that this compound can serve as a potential scaffold for the treatment of leishmaniasis and deserves further development.

Chemical structure and biological activity of the diazepines

PubMed Central

Danneberg, P.; Weber, K. H.

1983-01-01

1 Since the introduction of chlordiazepoxide and diazepam many diazepines have been developed. Use of these drugs is increasing and considerable knowledge has accumulated about their mechanisms of action. 2 The structural and pharmacological properties of these drugs are surveyed briefly. PMID:6140944

Preparation and biological activities of anti-HER2 monoclonal antibodies with fully core-fucosylated homogeneous bi-antennary complex-type glycans.

PubMed

Tsukimura, Wataru; Kurogochi, Masaki; Mori, Masako; Osumi, Kenji; Matsuda, Akio; Takegawa, Kaoru; Furukawa, Kiyoshi; Shirai, Takashi

2017-12-01

Recently, the absence of a core-fucose residue in the N-glycan has been implicated to be important for enhancing antibody-dependent cellular cytotoxicity (ADCC) activity of immunoglobulin G monoclonal antibodies (mAbs). Here, we first prepared anti-HER2 mAbs having two core-fucosylated N-glycan chains with the single G2F, G1aF, G1bF, or G0F structure, together with those having two N-glycan chains with a single non-core-fucosylated corresponding structure for comparison, and determined their biological activities. Dissociation constants of mAbs with core-fucosylated N-glycans bound to recombinant Fcγ-receptor type IIIa variant were 10 times higher than those with the non-core-fucosylated N-glycans, regardless of core glycan structures. mAbs with the core-fucosylated N-glycans had markedly reduced ADCC activities, while those with the non-core-fucosylated N-glycans had high activities. These results indicate that the presence of a core-fucose residue in the N-glycan suppresses the binding to the Fc-receptor and the induction of ADCC of anti-HER2 mAbs.

Designing synthetic RNAs to determine the relevance of structural motifs in picornavirus IRES elements

NASA Astrophysics Data System (ADS)

Fernandez-Chamorro, Javier; Lozano, Gloria; Garcia-Martin, Juan Antonio; Ramajo, Jorge; Dotu, Ivan; Clote, Peter; Martinez-Salas, Encarnacion

2016-04-01

The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems. Our data supports the hypothesis that structural sequestration of the pyrimidine-tract within a stable hairpin inactivates IRES activity, since the stronger the stability of the hairpin the higher the inhibition of protein synthesis. Destabilization of the stem-loop immediately upstream of the pyrimidine-tract also decreases IRES activity. Our work introduces a hybrid computational/experimental method to determine the importance of structural motifs for biological function. Specifically, we show the feasibility of using the software RNAiFold to design synthetic RNAs with particular sequence and structural motifs that permit subsequent experimental determination of the importance of such motifs for biological function.

How protein materials balance strength, robustness, and adaptability

PubMed Central

Buehler, Markus J.; Yung, Yu Ching

2010-01-01

Proteins form the basis of a wide range of biological materials such as hair, skin, bone, spider silk, or cells, which play an important role in providing key functions to biological systems. The focus of this article is to discuss how protein materials are capable of balancing multiple, seemingly incompatible properties such as strength, robustness, and adaptability. To illustrate this, we review bottom-up materiomics studies focused on the mechanical behavior of protein materials at multiple scales, from nano to macro. We focus on alpha-helix based intermediate filament proteins as a model system to explain why the utilization of hierarchical structural features is vital to their ability to combine strength, robustness, and adaptability. Experimental studies demonstrating the activation of angiogenesis, the growth of new blood vessels, are presented as an example of how adaptability of structure in biological tissue is achieved through changes in gene expression that result in an altered material structure. We analyze the concepts in light of the universality and diversity of the structural makeup of protein materials and discuss the findings in the context of potential fundamental evolutionary principles that control their nanoscale structure. We conclude with a discussion of multiscale science in biology and de novo materials design. PMID:20676305

Structure—activity relationships for insecticidal carbamates*

PubMed Central

Metcalf, Robert L.

1971-01-01

Carbamate insecticides are biologically active because of their structural complementarity to the active site of acetylcholinesterase (AChE) and their consequent action as substrates with very low turnover numbers. Carbamates behave as synthetic neurohormones that produce their toxic action by interrupting the normal action of AChE so that acetylcholine accumulates at synaptic junctions. The necessary properties for a suitable insecticidal carbamate are lipid solubility, suitable structural complementarity to AChE, and sufficient stability to multifunction-oxidase detoxification. The relationships between the structure and the activity of a large number of synthetic carbamates are analysed in detail, with particular attention to the second of these properties. PMID:5315358

Studies on Some Biologically Cobalt(II), Copper(II) and Zinc(II) Complexes With ONO, NNO and SNO Donor Pyrazinoylhydrazine-Derived Ligands

PubMed Central

Praveen, Marapaka; Sherazi, Syed K. A.

1998-01-01

Biologically active complexes of Co(II), Ni(II), Cu(II) and Zn(II) with novel ONO, NNO and SNO donor pyrazinoylhydrazine-derived compounds have been prepared and characterized on the basis of analytical data and various physicochemical studies. Distorted octahedral structures for all the complexes have been proposed. The synthesized ligands and their complexes have been screened for their antibacterial activity against bacterial species Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. The activity data show the metal complexes to be more active than the parent free ligands against one or more bacterial species. PMID:18475857

Diverse Molecular Targets for Chalcones with Varied Bioactivities

PubMed Central

Zhou, Bo; Xing, Chengguo

2015-01-01

Natural or synthetic chalcones with different substituents have revealed a variety of biological activities that may benefit human health. The underlying mechanisms of action, particularly with respect to the direct cellular targets and the modes of interaction with the targets, have not been rigorously characterized, which imposes challenges to structure-guided rational development of therapeutic agents or chemical probes with acceptable target-selectivity profile. This review summarizes literature evidence on chalcones’ direct molecular targets in the context of their biological activities. PMID:26798565

Potential Pharmacological Resources: Natural Bioactive Compounds from Marine-Derived Fungi

PubMed Central

Jin, Liming; Quan, Chunshan; Hou, Xiyan; Fan, Shengdi

2016-01-01

In recent years, a considerable number of structurally unique metabolites with biological and pharmacological activities have been isolated from the marine-derived fungi, such as polyketides, alkaloids, peptides, lactones, terpenoids and steroids. Some of these compounds have anticancer, antibacterial, antifungal, antiviral, anti-inflammatory, antioxidant, antibiotic and cytotoxic properties. This review partially summarizes the new bioactive compounds from marine-derived fungi with classification according to the sources of fungi and their biological activities. Those fungi found from 2014 to the present are discussed. PMID:27110799

Biology Notes.

ERIC Educational Resources Information Center

School Science Review, 1981

1981-01-01

Presents a computer program for analyzing diets, a game designed to supplement a topic on insects, a technique for demonstrating the role of ethene in fruit ripening, an apparatus for removing arthropods from soil samples, activities using cichlids, and an activity on bonds stabilizing protein structure. (JN)

QSAR studies of macrocyclic diterpenes with P-glycoprotein inhibitory activity.

PubMed

Sousa, Inês J; Ferreira, Maria-José U; Molnár, Joseph; Fernandes, Miguel X

2013-02-14

Multidrug resistance (MDR) represents a major limitation for cancer chemotherapy. There are several mechanisms of MDR but the most important is associated with P-glycoprotein (P-gp) overexpression. The development of modulators of P-gp that are able to re-establish drug sensitivity of resistant cells has been considered a promising approach for overcoming MDR. Macrocyclic lathyrane and jatrophane-type diterpenes from Euphorbia species were found to be strong MDR reversing agents. In this study we applied quantitative structure-activity relationship (QSAR) methodology in order to identify the most relevant molecular features of macrocyclic diterpenes with P-gp inhibitory activity and to determine which structural modifications can be performed to improve their activity. Using experimental biological data at two concentrations (4 and 40 μg/ml), we developed a QSAR model for a set of 51 bioactive diterpenic compounds which includes lathyrane and jatrophane-type diterpenes and another model just for jatrophanes. The cross-validation correlation values for all diterpenes QSAR models developed for biological activities at compound concentrations of 4 and 40 μg/ml were 0.758 and 0.729, respectively. Regarding the prediction ability, we get R²(pred) values of 0.765 and 0.534 for biological activities at compound concentrations of 4 and 40 μg/ml, respectively. Applying the cross-validation test to jatrophanes QSAR models, we obtained 0.680 and 0.787 for biological activities at compound concentrations of 4 and 40 μg/ml concentrations, respectively. For the same concentrations, the obtained R²(pred) values for jatrophanes models were 0.541 and 0.534, respectively. The obtained models were statistically valid and showed high prediction ability. Copyright © 2012 Elsevier B.V. All rights reserved.

Higher-order assembly of BRCC36–KIAA0157 is required for DUB activity and biological function

DOE PAGES

Zeqiraj, Elton; Tian, Lei; Piggott, Christopher  A.; ...

2015-09-03

BRCC36 is a Zn 2+-dependent deubiquitinating enzyme (DUB) that hydrolyzes lysine-63-linked ubiquitin chains as part of distinct macromolecular complexes that participate in either interferon signaling or DNA-damage recognition. The MPN + domain protein BRCC36 associates with pseudo DUB MPN– proteins KIAA0157 or Abraxas, which are essential for BRCC36 enzymatic activity. Here, to understand the basis for BRCC36 regulation, we have solved the structure of an active BRCC36-KIAA0157 heterodimer and an inactive BRCC36 homodimer. Structural and functional characterizations show how BRCC36 is switched to an active conformation by contacts with KIAA0157. Higher-order association of BRCC36 and KIAA0157 into a dimer ofmore » heterodimers (super dimers) was required for DUB activity and interaction with targeting proteins SHMT2 and RAP80. Lastly, these data provide an explanation of how an inactive pseudo DUB allosterically activates a cognate DUB partner and implicates super dimerization as a new regulatory mechanism underlying BRCC36 DUB activity, subcellular localization, and biological function.« less

Phytotoxicity of vulpia residues: III. Biological activity of identified allelochemicals from Vulpia myuros.

PubMed

An, M; Pratley, J E; Haig, T

2001-02-01

Twenty compounds identified in vulpia (Vulpia myuros) residues as allelochemicals were individually and collectively tested for biological activity. Each exhibited characteristic allelochemical behavior toward the test plant, i.e., inhibition at high concentrations and stimulation or no effect at low concentrations, but individual activities varied. Allelopathins present in large quantities, such as syringic, vanillic, and succinic acids, possessed low activity, while those present in small quantities, such as catechol and hydrocinnamic acid, possessed strong inhibitory activity. The concept of a phytotoxic strength index was developed for quantifying the biological properties of each individual allelopathin in a concise, comprehensive, and meaningful format. The individual contribution of each allelopathin, assessed by comparing the phytotoxic strength index to the overall toxicity of vulpia residues, was variable according to structure and was influenced by its relative proportion in the residue. The majority of compounds possessed low or medium biological activity and contributed most of the vulpia phytotoxicity, while compounds with high biological activity were in the minority and only present at low concentration. Artificial mixtures of these pure allelochemicals also produced phytotoxicity. There were additive/synergistic effects evident in the properties of these mixtures. One such mixture, formulated from allelochemicals found in the same proportions as occur in vulpia extract, produced stronger activity than another formulated from the same set of compounds but in equal proportions. These results suggest that the exploration of the relative composition of a cluster of allelopathins may be more important than simply focusing on the identification of one or two compounds with strong biological activity and that synergism is fundamental to the understanding of allelopathy.

Surface biofunctionalization and production of miniaturized sensor structures using aerosol printing technologies.

PubMed

Grunwald, Ingo; Groth, Esther; Wirth, Ingo; Schumacher, Julian; Maiwald, Marcus; Zoellmer, Volker; Busse, Matthias

2010-03-01

The work described in this paper demonstrates that very small protein and DNA structures can be applied to various substrates without denaturation using aerosol printing technology. This technology allows high-resolution deposition of various nanoscaled metal and biological suspensions. Before printing, metal and biological suspensions were formulated and then nebulized to form an aerosol which is aerodynamically focused on the printing module of the system in order to achieve precise structuring of the nanoscale material on a substrate. In this way, it is possible to focus the aerosol stream at a distance of about 5 mm from the printhead to the surface. This technology is useful for printing fluorescence-marked proteins and printing enzymes without affecting their biological activity. Furthermore, higher molecular weight DNA can be printed without shearing. The advantages, such as printing on complex, non-planar 3D structured surfaces, and disadvantages of the aerosol printing technology are also discussed and are compared with other printing technologies. In addition, miniaturized sensor structures with line thicknesses in the range of a few micrometers are fabricated by applying a silver sensor structure to glass. After sintering using an integrated laser or in an oven process, electrical conductivity is achieved within the sensor structure. Finally, we printed BSA in small micrometre-sized areas within the sensor structure using the same deposition system. The aerosol printing technology combined with material development offers great advantages for future-oriented applications involving biological surface functionalization on small areas. This is important for innovative biomedical micro-device development and for production solutions which bridge the disciplines of biology and electronics.

[A turning point in the knowledge of the structure-function-activity relations of elastin].

PubMed

Alix, A J

2001-01-01

In this review are presented the last new results of our research group dealing with the molecular structures (atomic level) of tropoelastin, elastin and elastin derived peptides studied by using essentially methods of bioinformatics (theoretical predictions and molecular modelling) linked to experimental circular dichroism spectroscopic studies. We already had characterized both the local secondary structure and some parts of the tertiary structure of the tropoelastin and elastin molecules (human, bovine...), by using either theoretical predictions (local secondary structure, linear epitopes...) and/or experimental data (optical spectroscopic methods: Raman scattering, infrared absorption, circular dichroism). Except the cross-linking regions which are in helical conformations, the whole tropoelastin structure displays a lot of beta-reverse turns which usually belong to irregular structures in proteins. These turns play a key role in other regularly structures orientation (alpha-helix, beta-strand), thus they are very important in the native protein 3D architecture. It is particularly true for human tropoelastin, because its sequence is rich in glycines and prolines, and these residues are frequently met in beta-turns (a beta-turn is made of four consecutive residues which are stabilized by an hydrogen bond). Several types of beta-turns can be defined with the dihedral angles values phi and psi of the two central residues. Thus, by using a very recent updated set of propensities for the amino acid residues to belong to given types of reverse beta-turns (extracted from a reference set of known 3-D structures of globular proteins), we have determined, (by using our home made software COUDES), for all possible tetrapeptides of the human tropoelastin sequence, the distribution and the characterization of the possible type of turns. Thus, it is shown that the locations and/or the types of these reverse beta-turns reveal a regularity and are not all random. This confirms our hypothesis that intra-molecular elasticity of tropoelastin could be explained by the possibility of transitions between conformations involving short beta-strands and beta-turns. This result is of great interest in the construction (by using molecular biology) of elastic biomaterials derived from the elastin sequence (particularly, the elastin derived peptides corresponding to the sequence exon 21--(exon 24--exon 24...). Our study permit also to predict the conformations of specific elastin derived peptides which could have interesting biological activity. Peptides resulting from the degradation of elastin, the insoluble polymer of tropoelastin and responsible for the elasticity of vertebrate tissues, can induce biological effects and notably the regulation of matrix metalloproteinases (MMP-s) activity. Recently, it was proposed that some elastin derived hexapeptides resulting from circular permutations of VGVAPG (a three fold repetition sequence in exon 24 of human tropoelastin) possess MMP-1 production and activation regulation properties. This effect depends on the presence of the tropoelastin specific membraneous receptor 67 KDa EBP (Elastin Binding Protein). Our results obtained by using both circular dichroism spectroscopy and linear predictions confirmed the hypothesis of a structure dependent mechanism with a possibly occurring type VIII beta-turn on the first four residues of the GXXPG sequence consensus which is only present among all active peptides. Thus, we have performed extensive molecular dynamics studies, in both implicit and explicit solvent, on these active and inactive elastin derived hexapeptides. Using our own analysis method of pattern recognition of the types of the beta-reverse-turns followed during the molecular dynamics trajectory, we found that active and inactive peptides effectively form two well distinct conformational groups in which active peptides preferentially adopt conformation close to type VIII GXXP (beta-reverse-turn. The structural role of the C terminal G residue could also be explained. Additional molecular simulations on (VGVAPG)2 and (VGVAPG)3 show the formation of two or three GXXP tetrapeptides adopting a structure close to type VIII beta-reverse-turn, suggesting a local conformational preference for this motif. This observation of a specific structural single and/or repeated motif is in agreement with the circular dichroism spectra of the involved (VGVAPG)1, (VGVAPG)2 and (VGVAPG)3 peptides and then it can be proposed that their biological activities have to be linear. The final aim of this type of work is to understand more about the sequence/structure/function/activity relationships of those structured peptides in order to propose specific sequences (corresponding to specific structures) for best biological activity results.

Natural Products from the Lithistida: A Review of the Literature since 2000

PubMed Central

Winder, Priscilla L.; Pomponi, Shirley A.; Wright, Amy E.

2011-01-01

Lithistid sponges are known to produce a diverse array of compounds ranging from polyketides, cyclic and linear peptides, alkaloids, pigments, lipids, and sterols. A majority of these structurally complex compounds have very potent and interesting biological activities. It has been a decade since a thorough review has been published that summarizes the literature on the natural products reported from this amazing sponge order. This review provides an update on the current taxonomic classification of the Lithistida, describes structures and biological activities of 131 new natural products, and discusses highlights from the total syntheses of 16 compounds from marine sponges of the Order Lithistida providing a compilation of the literature since the last review published in 2002. PMID:22363244

Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review.

PubMed

He, Xirui; Wang, Xiaoxiao; Fang, Jiacheng; Chang, Yu; Ning, Ning; Guo, Hao; Huang, Linhong; Huang, Xiaoqiang; Zhao, Zefeng

2017-04-01

Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion's Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Heterocyclic cationic gemini surfactants: a comparative overview of their synthesis, self-assembling, physicochemical, and biological properties.

PubMed

Sharma, Vishnu Dutt; Ilies, Marc A

2014-01-01

Gemini surfactants (GS) are presently receiving substantial attention due to their special self-assembling properties and unique interfacial activity. This comprehensive review is focused on positively charged heterocyclic GS, presenting their major synthetic access routes and examining the impact of structural elements on physicochemical and aggregation properties of this class of amphiphiles. Interaction of geminis surfactants with cells and their biological properties as novel transfection agents are emphasized through a detailed structure-activity relationship analysis. Throughout the review we have also presented the properties of selected ammonium GS, simple surfactants and lipid congeners, in order to emphasize the advantages conferred by using heterocyclic polar heads in GS design. © 2012 Wiley Periodicals, Inc.

Solid-Phase and Microwave-Assisted Syntheses of 2,5-Diketopiperazines: Small Molecules with Great Potential

PubMed Central

O'Neill, J.C.; Blackwell, H. E.

2008-01-01

Diketopiperazines (DKPs) are a well-known class of heterocycles that have recently emerged as a promising biologically active scaffold. Solid-phase organic synthesis has become an important tool in the combinatorial exploration of these privileged structures, expediting the synthesis and, therefore, the discovery of active compounds. To date, certain DKPs have shown potent activities against a range of diseases and biological phenomena, including bacterial infections, various cancers, asthma, infertility, premature labor, and HIV. Recent applications of solid-phase DKP synthesis, with a particular focus on cyclative cleavage and microwave-assisted reactions, are highlighted herein. PMID:18288948

Human skin gene expression: Natural (trans) resveratrol versus five resveratrol analogs for dermal applications.

PubMed

Lephart, Edwin D; Andrus, Merritt B

2017-09-01

Resveratrol (RV) is a polyphenolic compound naturally produced by plants. Polyphenolic compounds incorporated into medicinal products are beneficial but, RV is rapidly metabolized with an associated decline in biological activity. This study tested RV as the standard and compared five structurally modified RV analogs: butyrate, isobutyrate, palmitoate, acetate, and diacetate (to improve functionality) at 1% concentration(s) for 24 h in epiderm full thickness cultures by gene array/qPCR mRNA analysis. When silent mating type information regulation 2 homolog 1, extracellular elements (collagen1A1, 3A1, 4A1; elastin, tissue inhibitor of matrix metalloproteinase 1, fibrillin 1 laminin beta1 and matrix metalloproteinase 9), anti-aging and aging genes, inflammatory biomarkers (interleukin-1A [IL1A], IL1R2, IL-6 and IL-8), nerve growth factor, and the antioxidants (proliferating cell nuclear antigen, catalase, superoxide dismutase and metallothionein 1H/2H) were evaluated, ranking each from highest-to-lowest for gene expression: butyrate > isobutyrate > diacetate > acetate > palmitoate. This study showed that the butyrate and isobutyrate analogs are more biologically active compared to resveratrol and have potential use in topical applications to improve dermal and other health applications. Impact statement Resveratrol has been reported to have a wide variety of health benefits but its rapid metabolism especially after oral ingestion results in very low bioavailability. Notably, the first human skin gene expression study of resveratrol was not published until 2014. The purpose of this study was to determine if increased stability and biological activity could be obtained by modifying the chemical structure of natural (trans) resveratrol and quantifying human gene expression by qPCR of skin biomarkers that enhance dermal health. Five resveratrol analogs were synthesized that increased their lipophilic index to enhance tissue penetration and augment biological activities on the measured parameters that expand the current knowledge of structure/function relationships. The butyrate and isobutyrate modifications displayed gene expression values significantly above resveratrol and suggest that oral application of these and potentially other resveratrol analogs may yield similar results to improve stability and biological activity to benefit/address various disorders/diseases.

CHEMICAL STRUCTURE INDEXING OF TOXICITY DATA ON THE INTERNET: MOVING TOWARDS A FLAT WORLD

EPA Science Inventory

Standardized chemical structure annotation of public toxicity databases and information resources is playing an increasingly important role in the 'flattening' and integration of diverse sets of biological activity data on the Internet. This review discusses public initiatives th...

An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents.

PubMed

Arshad, Laiba; Haque, Md Areeful; Abbas Bukhari, Syed Nasir; Jantan, Ibrahim

2017-04-01

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.

Structural characterization of novel L-galactose-containing oligosaccharide subunits of jojoba seed xyloglucans.

PubMed

Hantus, S; Pauly, M; Darvill, A G; Albersheim, P; York, W S

1997-10-28

Jojoba seed xyloglucan was shown to be a convenient source of biologically active xyloglucan oligosaccharides that contain both L- and D-galactosyl residues [E. Zablackis et al., Science, 272 (1996) 1808-1810]. Oligosaccharides were isolated by liquid chromatography of the mixture of oligosaccharides generated by treating jojoba seed xyloglucan with a beta-(1-->4)-endoglucanase. The purified oligosaccharides were reduced with NaBH4, converting them to oligoglycosyl alditol derivatives that were structurally characterized by a combination of mass spectrometry and 2-dimensional NMR spectroscopy. This analysis established that jojoba xyloglucan oligosaccharides contain the novel side-chain [alpha-L-Gal p-(1-->2)-beta-D-Galp-(1-->2)-alpha-D-Xyl p-(1-->6)-], which is structurally homologous to the fucose-containing side-chain [alpha-L-Fucp-(1-->2)-beta-D-Galp-(1-->2)-alpha-D-Xyl p-(1-->6)-] found in other biologically active xyloglucan oligosaccharides.

Structural diversity of marine cyclic peptides and their molecular mechanisms for anticancer, antibacterial, antifungal, and other clinical applications.

PubMed

Lee, Yeji; Phat, Chanvorleak; Hong, Soon-Cheol

2017-09-01

Many cyclic peptides and analogues derived from marine sources are known to possess biological properties, including anticancer, antitumor, antibacterial, antifungal, antiparasitic, anti-inflammation, anti-proliferative, anti-hypertensive, cytotoxic, and antibiotic properties. These compounds demonstrate different activities and modes of action according to their structure such as cyclic oligopeptide, cyclic lipopeptide, cyclic glycopeptide and cyclic depsipeptide. The recent advances in application of the above-mentioned cyclic peptides were reported in dolastatins, soblidotin, didemnin B, aplidine, salinosporamide A, kahalalide F and bryostatin 1 and they are currently in clinical trials. These cyclic peptides are possible novel drugs discovered and developed from marine origin. Literature data concerning the potential properties of marine cyclic peptides were reviewed here, and the structural diversity and biological activities of marine cyclic peptides are discussed in relation to the molecular mechanisms of these marine cyclic peptides. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of using challenging tasks in biology classrooms on students' cognitive knowledge structure: an empirical video study

NASA Astrophysics Data System (ADS)

Nawani, Jigna; Rixius, Julia; Neuhaus, Birgit J.

2016-08-01

Empirical analysis of secondary biology classrooms revealed that, on average, 68% of teaching time in Germany revolved around processing tasks. Quality of instruction can thus be assessed by analyzing the quality of tasks used in classroom discourse. This quasi-experimental study analyzed how teachers used tasks in 38 videotaped biology lessons pertaining to the topic 'blood and circulatory system'. Two fundamental characteristics used to analyze tasks include: (1) required cognitive level of processing (e.g. low level information processing: repetiition, summary, define, classify and high level information processing: interpret-analyze data, formulate hypothesis, etc.) and (2) complexity of task content (e.g. if tasks require use of factual, linking or concept level content). Additionally, students' cognitive knowledge structure about the topic 'blood and circulatory system' was measured using student-drawn concept maps (N = 970 students). Finally, linear multilevel models were created with high-level cognitive processing tasks and higher content complexity tasks as class-level predictors and students' prior knowledge, students' interest in biology, and students' interest in biology activities as control covariates. Results showed a positive influence of high-level cognitive processing tasks (β = 0.07; p < .01) on students' cognitive knowledge structure. However, there was no observed effect of higher content complexity tasks on students' cognitive knowledge structure. Presented findings encourage the use of high-level cognitive processing tasks in biology instruction.

Can Climate Change Enhance Biology Lessons? A Quasi-Experiment

ERIC Educational Resources Information Center

Monroe, Martha C.; Hall, Stephanie; Li, Christine Jie

2016-01-01

Climate change is a highly charged topic that some adults prefer to ignore. If the same holds true for secondary students, teachers could be challenged to teach about climate change. We structured one activity about the biological concepts of carbon cycle and carbon sequestration in two ways: with and without mention of climate change. Results…

Improving Exam Performance in Introductory Biology through the Use of Preclass Reading Guides

ERIC Educational Resources Information Center

Lieu, Rebekah; Wong, Ashley; Asefirad, Anahita; Shaffer, Justin F.

2017-01-01

High-structure courses or flipped courses require students to obtain course content before class so that class time can be used for active-learning exercises. While textbooks are used ubiquitously in college biology courses for content dissemination, studies have shown that students frequently do not read their textbooks. To address this issue, we…

Diffraction Techniques in Structural Biology

PubMed Central

Egli, Martin

2016-01-01

A detailed understanding of chemical and biological function and the mechanisms underlying the molecular activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy, and neutron diffraction are well established and they have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last 20 years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches, and high-speed computing and visualization, now provide specialists and nonspecialists alike with a steady flow of molecular images of unprecedented detail. The present unit combines a general overview of diffraction methods with a detailed description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis, and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. PMID:27248784

Computational challenges of structure-based approaches applied to HIV.

PubMed

Forli, Stefano; Olson, Arthur J

2015-01-01

Here, we review some of the opportunities and challenges that we face in computational modeling of HIV therapeutic targets and structural biology, both in terms of methodology development and structure-based drug design (SBDD). Computational methods have provided fundamental support to HIV research since the initial structural studies, helping to unravel details of HIV biology. Computational models have proved to be a powerful tool to analyze and understand the impact of mutations and to overcome their structural and functional influence in drug resistance. With the availability of structural data, in silico experiments have been instrumental in exploiting and improving interactions between drugs and viral targets, such as HIV protease, reverse transcriptase, and integrase. Issues such as viral target dynamics and mutational variability, as well as the role of water and estimates of binding free energy in characterizing ligand interactions, are areas of active computational research. Ever-increasing computational resources and theoretical and algorithmic advances have played a significant role in progress to date, and we envision a continually expanding role for computational methods in our understanding of HIV biology and SBDD in the future.

Diffraction Techniques in Structural Biology

PubMed Central

Egli, Martin

2010-01-01

A detailed understanding of chemical and biological function and the mechanisms underlying the activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy and neutron diffraction are well established and have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last 20 years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches and high-speed computing and visualization, now provide specialists and non-specialists alike with a steady flow of molecular images of unprecedented detail. The present chapter combines a general overview of diffraction methods with a step-by-step description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. PMID:20517991

Diffraction Techniques in Structural Biology.

PubMed

Egli, Martin

2016-06-01

A detailed understanding of chemical and biological function and the mechanisms underlying the molecular activities ultimately requires atomic-resolution structural data. Diffraction-based techniques such as single-crystal X-ray crystallography, electron microscopy, and neutron diffraction are well established and they have paved the road to the stunning successes of modern-day structural biology. The major advances achieved in the last twenty years in all aspects of structural research, including sample preparation, crystallization, the construction of synchrotron and spallation sources, phasing approaches, and high-speed computing and visualization, now provide specialists and nonspecialists alike with a steady flow of molecular images of unprecedented detail. The present unit combines a general overview of diffraction methods with a detailed description of the process of a single-crystal X-ray structure determination experiment, from chemical synthesis or expression to phasing and refinement, analysis, and quality control. For novices it may serve as a stepping-stone to more in-depth treatises of the individual topics. Readers relying on structural information for interpreting functional data may find it a useful consumer guide. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

Chemistry and biological activity of platinum amidine complexes.

PubMed

Michelin, Rino A; Sgarbossa, Paolo; Sbovata, Silvia Mazzega; Gandin, Valentina; Marzano, Cristina; Bertani, Roberta

2011-07-04

Platinum amidine complexes represent a new class of potential antitumor drugs that contain the imino moiety HN=C(sp(2)) bonded to the platinum center. They can be related to the iminoether derivatives, which were recently shown to be the first Pt(II) compounds with a trans configuration endowed with anticancer activity. The chemical and biological properties of platinum amidine complexes, and more generally of platinum imino derivatives, can be rationally modified through suitable synthetic procedures with the aim of improving their cytotoxicity and antitumor activity. The addition of protic nucleophiles to nitriles coordinated to platinum in various oxidation states can offer a wide variety of complexes with chemical, structural, and physical properties specifically tuned for a more efficacious biological response. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Experimental and molecular modeling investigation of isopropyl 4-(biphenyl-4-Yl)-2,6,6-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate

NASA Astrophysics Data System (ADS)

Yıldırım, Sema Öztürk; ćetin, Gökalp; Büyükmumcu, Zeki; Şimşek, Rahime; Şafak, Cihat; Butcher, Ray J.; Pekdur, Özlem Savaş

2018-02-01

The most important effect of 1,4-dihydropyridine (1,4-DHP) derivatives with various biological activities is to reduce the influx of extracellular Ca2+ ions. Because of this feature, many 1,4-DHP derivatives have been identified as potent calcium channel blockers and have been included in the treatment as antihypertensive agents. On the other hand, the biphenyl group is an important group in the molecule of biologically active compounds. The active compounds are obtained by introducing the biphenyl group into the structure of various compounds. In this study, the biphenyl group was introduced into the 1,4-DHP ring to reach to hexahydroquinoline (HHQ) derivative as an active calcium channel blocker compound. The structure of the compound was proved by IR, 1H-NMR, Mass spectroscopy, X-ray crystallography and elemental analysis. The cytotoxic properties of the compound has been determined, and biological activity assays continue. The crystal structure of C28H31NO3 was determined by single crystal X-ray diffraction: monoclinic, space group C c, a = 11.9713(3) Å, b = 18.7893(5) Å, c = 10.7358(3) Å, β = 102.411(4)°, Z = 4. The title molecule is twisted with the dihedral angle between two phenyl rings being 50.86(10)°. The optimized geometries of the title compound have been obtained employing DFT method. The calculated geometrical parameters were found to be in agreement with the experimental data.

Genetics and the unity of biology. Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1988-12-31

International Congresses of Genetics, convened just once every five years, provide a rare opportunity for overview in the field of genetic engineering. The Congress, held August 20-27, 1988 in Toronto, Canada focused on the theme Genetics and the Unity of Biology, which was chosen because the concepts of modern genetics have provided biology with a unifying theoretical structure. This program guide contains a schedule of all Congress activities and a listing of all Symposia, Workshops and Poster Sessions held.

Discovering the intelligence in molecular biology.

PubMed

Uberbacher, E

1995-12-01

The Third International Conference on Intelligent Systems in Molecular Biology was truly an outstanding event. Computational methods in molecular biology have reached a new level of maturity and utility, resulting in many high-impact applications. The success of this meeting bodes well for the rapid and continuing development of computational methods, intelligent systems and information-based approaches for the biosciences. The basic technology, originally most often applied to 'feasibility' problems, is now dealing effectively with the most difficult real-world problems. Significant progress has been made in understanding protein-structure information, structural classification, and how functional information and the relevant features of active-site geometry can be gleaned from structures by automated computational approaches. The value and limits of homology-based methods, and the ability to classify proteins by structure in the absence of homology, have reached a new level of sophistication. New methods for covariation analysis in the folding of large structures such as RNAs have shown remarkably good results, indicating the long-term potential to understand very complicated molecules and multimolecular complexes using computational means. Novel methods, such as HMMs, context-free grammars and the uses of mutual information theory, have taken center stage as highly valuable tools in our quest to represent and characterize biological information. A focus on creative uses of intelligent systems technologies and the trend toward biological application will undoubtedly continue and grow at the 1996 ISMB meeting in St Louis.

Lessons from 455 Fusarium polyketide synthases

USDA-ARS?s Scientific Manuscript database

In fungi, polyketide synthases (PKSs) synthesize a structurally diverse array of secondary metabolites (SMs) with a range of biological activities. The most studied SMs are toxic to animals and/or plants, alter plant growth, have beneficial pharmaceutical activities, and/or are brightly colored pigm...

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY: AN EXPANDED VIEW OF CHEMICAL TOXICITY

EPA Science Inventory

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. T...

Anticancer and cancer preventive properties of marine polysaccharides: some results and prospects.

PubMed

Fedorov, Sergey N; Ermakova, Svetlana P; Zvyagintseva, Tatyana N; Stonik, Valentin A

2013-12-02

Many marine-derived polysaccharides and their analogues have been reported as showing anticancer and cancer preventive properties. These compounds demonstrate interesting activities and special modes of action, differing from each other in both structure and toxicity profile. Herein, literature data concerning anticancer and cancer preventive marine polysaccharides are reviewed. The structural diversity, the biological activities, and the molecular mechanisms of their action are discussed.

New Peptides Isolated from Marine Cyanobacteria, an Overview over the Past Decade

PubMed Central

Mi, Yue; Zhang, Jinrong; He, Shan; Yan, Xiaojun

2017-01-01

Marine cyanobacteria are significant sources of structurally diverse marine natural products with broad biological activities. In the past 10 years, excellent progress has been made in the discovery of marine cyanobacteria-derived peptides with diverse chemical structures. Most of these peptides exhibit strong pharmacological activities, such as neurotoxicity and cytotoxicity. In the present review, we summarized peptides isolated from marine cyanobacteria since 2007. PMID:28475149

Response of soil microbial activities and microbial community structure to vanadium stress.

PubMed

Xiao, Xi-Yuan; Wang, Ming-Wei; Zhu, Hui-Wen; Guo, Zhao-Hui; Han, Xiao-Qing; Zeng, Peng

2017-08-01

High levels of vanadium (V) have long-term, hazardous impacts on soil ecosystems and biological processes. In the present study, the effects of V on soil enzymatic activities, basal respiration (BR), microbial biomass carbon (MBC), and the microbial community structure were investigated through 12-week greenhouse incubation experiments. The results showed that V content affected soil dehydrogenase activity (DHA), BR, and MBC, while urease activity (UA) was less sensitive to V stress. The average median effective concentration (EC 50 ) thresholds of V were predicted using a log-logistic dose-response model, and they were 362mgV/kg soil for BR and 417mgV/kg soil for DHA. BR and DHA were more sensitive to V addition and could be used as biological indicators for soil V pollution. According to a polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis, the structural diversity of the microbial community decreased for soil V contents ranged between 254 and 1104mg/kg after 1 week of incubation. As the incubation time increased, the diversity of the soil microbial community structure increased for V contents ranged between 354 and 1104mg/kg, indicating that some new V-tolerant bacterial species might have replicated under these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Object-oriented parsing of biological databases with Python.

PubMed

Ramu, C; Gemünd, C; Gibson, T J

2000-07-01

While database activities in the biological area are increasing rapidly, rather little is done in the area of parsing them in a simple and object-oriented way. We present here an elegant, simple yet powerful way of parsing biological flat-file databases. We have taken EMBL, SWISSPROT and GENBANK as examples. EMBL and SWISS-PROT do not differ much in the format structure. GENBANK has a very different format structure than EMBL and SWISS-PROT. Extracting the desired fields in an entry (for example a sub-sequence with an associated feature) for later analysis is a constant need in the biological sequence-analysis community: this is illustrated with tools to make new splice-site databases. The interface to the parser is abstract in the sense that the access to all the databases is independent from their different formats, since parsing instructions are hidden.

A Short Review of the Generation of Molecular Descriptors and Their Applications in Quantitative Structure Property/Activity Relationships.

PubMed

Sahoo, Sagarika; Adhikari, Chandana; Kuanar, Minati; Mishra, Bijay K

2016-01-01

Synthesis of organic compounds with specific biological activity or physicochemical characteristics needs a thorough analysis of the enumerable data set obtained from literature. Quantitative structure property/activity relationships have made it simple by predicting the structure of the compound with any optimized activity. For that there is a paramount data set of molecular descriptors (MD). This review is a survey on the generation of the molecular descriptors and its probable applications in QSP/AR. Literatures have been collected from a wide class of research journals, citable web reports, seminar proceedings and books. The MDs were classified according to their generation. The applications of the MDs on the QSP/AR have also been reported in this review. The MDs can be classified into experimental and theoretical types, having a sub classification of the later into structural and quantum chemical descriptors. The structural parameters are derived from molecular graphs or topology of the molecules. Even the pixel of the molecular image can be used as molecular descriptor. In QSPR studies the physicochemical properties include boiling point, heat capacity, density, refractive index, molar volume, surface tension, heat of formation, octanol-water partition coefficient, solubility, chromatographic retention indices etc. Among biological activities toxicity, antimalarial activity, sensory irritant, potencies of local anesthetic, tadpole narcosis, antifungal activity, enzyme inhibiting activity are some important parameters in the QSAR studies. The classification of the MDs is mostly generic in nature. The application of the MDs in QSP/AR also has a generic link. Experimental MDs are more suitable in correlation analysis than the theoretical ones but are more expensive for generation. In advent of sophisticated computational tools and experimental design proliferation of MDs is inevitable, but for a highly optimized MD, studies on generation of MD is an unending process.

Biocatalysis and biomimetics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burrington, J.D.; Clark, D.S.

1989-01-01

This book presents recent advances in catalytic science and biotechnology. The chapters illustrate how many of the key challenges in biotechnology can be addressed by bringing together traditionally separate disciplines within chemistry and biology. The authors focus on emerging enabling technologies at the interfaces of catalysis and biology that will provide new opportunities for the chemicals industries. Key aspects to be presented within this major theme of catalysis and biotechnology are biomimetics and hybrid catalysts, biocatalytic applications of computers and expert systems, enzyme solid-state structure and immobilization, enzyme structure-activity relationships, and the use of enzymes under novel conditions.

The structural biology of phenazine biosynthesis

PubMed Central

Blankenfeldt, Wulf; Parsons, James F.

2014-01-01

The phenazines are a class of over 150 nitrogen-containing aromatic compounds of bacterial and archeal origin. Their redox properties not only explain their activity as broad-specificity antibiotics and virulence factors but also enable them to function as respiratory pigments, thus extending their importance to the primary metabolism of phenazine-producing species. Despite their discovery in the mid-19th century, the molecular mechanisms behind their biosynthesis have only been unraveled in the last decade. Here, we review the contribution of structural biology that has led to our current understanding of phenazine biosynthesis. PMID:25215885

Recent advances of pyrrolopyridines derivatives: a patent and literature review.

PubMed

El-Gamal, Mohammed I; Anbar, Hanan S

2017-05-01

Several pyrrolopyridines or azaindoles have been reported in the literature as biologically-active molecules. Most of them are anticancer agents, and few possess other therapeutic effects. Areas covered: The most recent biologically-active pyrrolopyridine derivatives have been reviewed from the patents and research articles published from 2010 to the mid of 2016. Their structural and biological features have been explained. In general, the pyrrolopyridine scaffold mimics the purine ring of the ATP molecule. So the well-designed pyrrolopyridine analogues can successfully act as kinase inhibitors for treatment of cancer and/or other diseases. The most successful pyrrolopyridine derivative that is currently used in the market is vemurafenib, which is used for treatment of melanoma. Its chemical and biological features have been reviewed and explained. Expert opinion: The heterocyclic pyrrolopyridine nucleus mimics the purine ring of ATP. So they can work as inhibitors of the kinase at hinge region. Due to the structural similarity with ATP, these pyrrolopyridine derivatives are estimated to be non-selective kinase inhibitors. The selectivity is conferred mainly from the different substituents attached to the azaindole nucleus. More details are presented in the 'Expert Opinion' section at the end of this article. This section covers the chemistry and the biological properties of therapeutically-efficient pyrrolopyridine-possessing compounds.

Engineering of routes to heparin and related polysaccharides.

PubMed

Bhaskar, Ujjwal; Sterner, Eric; Hickey, Anne Marie; Onishi, Akihiro; Zhang, Fuming; Dordick, Jonathan S; Linhardt, Robert J

2012-01-01

Anticoagulant heparin has been shown to possess important biological functions that vary according to its fine structure. Variability within heparin's structure occurs owing to its biosynthesis and animal tissue-based recovery and adds another dimension to its complex polymeric structure. The structural variations in chain length and sulfation patterns mediate its interaction with many heparin-binding proteins, thereby eliciting complex biological responses. The advent of novel chemical and enzymatic approaches for polysaccharide synthesis coupled with high throughput combinatorial approaches for drug discovery have facilitated an increased effort to understand heparin's structure-activity relationships. An improved understanding would offer potential for new therapeutic development through the engineering of polysaccharides. Such a bioengineering approach requires the amalgamation of several different disciplines, including carbohydrate synthesis, applied enzymology, metabolic engineering, and process biochemistry.

Chemical and structural biology of protein lysine deacetylases

PubMed Central

YOSHIDA, Minoru; KUDO, Norio; KOSONO, Saori; ITO, Akihiro

2017-01-01

Histone acetylation is a reversible posttranslational modification that plays a fundamental role in regulating eukaryotic gene expression and chromatin structure/function. Key enzymes for removing acetyl groups from histones are metal (zinc)-dependent and NAD+-dependent histone deacetylases (HDACs). The molecular function of HDACs have been extensively characterized by various approaches including chemical, molecular, and structural biology, which demonstrated that HDACs regulate cell proliferation, differentiation, and metabolic homeostasis, and that their alterations are deeply involved in various human disorders including cancer. Notably, drug discovery efforts have achieved success in developing HDAC-targeting therapeutics for treatment of several cancers. However, recent advancements in proteomics technology have revealed much broader aspects of HDACs beyond gene expression control. Not only histones but also a large number of cellular proteins are subject to acetylation by histone acetyltransferases (HATs) and deacetylation by HDACs. Furthermore, some of their structures can flexibly accept and hydrolyze other acyl groups on protein lysine residues. This review mainly focuses on structural aspects of HDAC enzymatic activity regulated by interaction with substrates, co-factors, small molecule inhibitors, and activators. PMID:28496053

Structures and physical properties of gaseous metal cationized biological ions.

PubMed

Burt, Michael B; Fridgen, Travis D

2012-01-01

Metal chelation can alter the activity of free biomolecules by modifying their structures or stabilizing higher energy tautomers. In recent years, mass spectrometric techniques have been used to investigate the effects of metal complexation with proteins, nucleobases and nucleotides, where small conformational changes can have significant physiological consequences. In particular, infrared multiple photon dissociation spectroscopy has emerged as an important tool for determining the structure and reactivity of gas-phase ions. Unlike other mass spectrometric approaches, this method is able to directly resolve structural isomers using characteristic vibrational signatures. Other activation and dissociation methods, such as blackbody infrared radiative dissociation or collision-induced dissociation can also reveal information about the thermochemistry and dissociative pathways of these biological ions. This information can then be used to provide information about the structures of the ionic complexes under study. In this article, we review the use of gas-phase techniques in characterizing metal-bound biomolecules. Particular attention will be given to our own contributions, which detail the ability of metal cations to disrupt nucleobase pairs, direct the self-assembly of nucleobase clusters and stabilize non-canonical isomers of amino acids.

Enhancing Bioremediation of Oil-contaminated Soils by Controlling Nutrient Transport using Dual Characteristics of Soil Pore Structure

NASA Astrophysics Data System (ADS)

Mori, Y.; Suetsugu, A.; Matsumoto, Y.; Fujihara, A.; Suyama, K.; Miyamoto, T.

2012-12-01

Soil structure is heterogeneous with cracks or macropores allowing bypass flow, which may lead to applied chemicals avoiding interaction with soil particles or the contaminated area. We investigated the bioremediation efficiency of oil-contaminated soils by applying suction at the bottom of soil columns during bioremediation. Unsaturated flow conditions were investigated so as to avoid bypass flow and achieve sufficient dispersion of chemicals in the soil column. The boundary conditions at the bottom of the soil columns were 0 kPa and -3 kPa, and were applied to a volcanic ash soil with and without macropores. Unsaturated flow was achieved with -3 kPa and an injection rate of 1/10 of the saturated hydraulic conductivity. The resultant biological activities of the effluent increased dramatically in the unsaturated flow with macropores condition. Unsaturated conditions prevented bypass flow and allowed dispersion of the injected nutrients. Unsaturated flow achieved 60-80% of saturation, which enhanced biological activity in the soil column. Remediation results were better for unsaturated conditions because of higher biological activity. Moreover, unsaturated flow with macropores achieved uniform remediation efficiency from upper through lower positions in the column. Finally, taking the applied solution volume into consideration, unsaturated flow with -3 kPa achieved 10 times higher efficiency when compared with conventional saturated flow application. These results suggest that effective use of nutrients or remediation chemicals is possible by avoiding bypass flow and enhancing biological activity using relatively simple and inexpensive techniques.

The recombinant expression and activity detection of MAF-1 fusion protein.

PubMed

Fu, Ping; Wu, Jianwei; Gao, Song; Guo, Guo; Zhang, Yong; Liu, Jian

2015-10-01

This study establishes the recombinant expression system of MAF-1 (Musca domestica antifungal peptide-1) and demonstrates the antifungal activity of the expression product and shows the relationship between biological activity and structure. The gene segments on mature peptide part of MAF-1 were cloned, based on the primers designed according to the cDNA sequence of MAF-1. We constructed the recombinant prokaryotic expression plasmid using prokaryotic expression vector (pET-28a(+)) and converted it to the competent cell of BL21(DE3) to gain recombinant MAF-1 fusion protein with His tag sequence through purifying affinity chromatographic column of Ni-NTA. To conduct the Western Blotting test, recombinant MAF-1 fusion protein was used to produce the polyclonal antibody of rat. The antifungal activity of the expression product was detected using Candida albicans (ATCC10231) as the indicator. The MAF-1 recombinant fusion protein was purified to exhibit obvious antifungal activity, which lays the foundation for the further study of MAF-1 biological activity, the relationship between structure and function, as well as control of gene expression.

Structural characterization of tetranortriterpenes from Pseudrocedrela kotschyi and Trichilia emetica and study of their activity towards the chaperone Hsp90.

PubMed

Piaz, Fabrizio Dal; Malafronte, Nicola; Romano, Adriana; Gallotta, Dario; Belisario, Maria Antonietta; Bifulco, Giuseppe; Gualtieri, Maria Josefine; Sanogo, Rokia; Tommasi, Nunziatina De; Pisano, Claudio

2012-03-01

Investigation of roots extracts Pseudrocedrela kotschyi and Trichilia emetica led to identification of 5 limonoid derivatives, Kotschyins D-H, and 11 known compounds. Their structures were elucidated by extensive 1D and 2D NMR experiments in conjunction with mass spectrometry. A surface plasmon resonance (SPR) approach was adopted to screen their Hsp90 binding capability and kotschyin D showed a significant affinity for the chaperone. Therefore, the characterization of the biological activity of kotschyin D by means of a panel of chemical and biological approaches, including limited proteolysis, molecular docking and biochemical and cellular assays, was performed. Our result indicated this compound as a type of client selective Hsp90 inhibitor, directly binding to the middle domain of the protein and possibly preventing its interaction with the activator of Hsp90 ATPase 1 (Aha1). Copyright © 2011 Elsevier Ltd. All rights reserved.

Synthesis, biological evaluation, and structure-activity relationship of clonazepam, meclonazepam, and 1,4-benzodiazepine compounds with schistosomicidal activity.

PubMed

Menezes, Carla M S; Rivera, Gildardo; Alves, Marina A; do Amaral, Daniel N; Thibaut, Jean Pierre B; Noël, François; Barreiro, Eliezer J; Lima, Lídia M

2012-06-01

The inherent morbidity and mortality caused by schistosomiasis is a serious public health problem in developing countries. Praziquantel is the only drug in therapeutic use, leading to a permanent risk of parasite resistance. In search for new schistosomicidal drugs, meclonazepam, the 3-methyl-derivative of clonazepam, is still considered an interesting lead-candidate because it has a proven schistosomicidal effect in humans but adverse effects on the central nervous system did not allow its clinical use. Herein, the synthesis, in vitro biological evaluation, and molecular modeling of clonazepam, meclonazepam, and analogues are reported to establish the first structure-activity relationship for schistosomicidal benzodiazepines. Our findings indicate that the amide moiety [N(1) H-C(2) (=O)] is the principal pharmacophoric unit of 1,4-benzodiazepine schistosomicidal compounds and that substitution on the amide nitrogen atom (N(1) position) is not tolerated. © 2012 John Wiley & Sons A/S.

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials.

PubMed

Choudhary, Alka; Naughton, Lynn M; Montánchez, Itxaso; Dobson, Alan D W; Rai, Dilip K

2017-08-28

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012-2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds.

Biology and Systematics of Echinococcus.

PubMed

Thompson, R C A

2017-01-01

The biology of Echinococcus, the causative agent of echinococcosis (hydatid disease) is reviewed with emphasis on the developmental biology of the adult and metacestode stages of the parasite. Major advances include determining the origin, structure and functional activities of the laminated layer and its relationship with the germinal layer; and the isolation, in vitro establishment and characterization of the multipotential germinal cells. Future challenges are to identify the mechanisms that provide Echinococcus with its unique developmental plasticity and the nature of activities at the parasite-host interface, particularly in the definitive host. The revised taxonomy of Echinococcus is presented and the solid nomenclature it provides will be essential in understanding the epidemiology of echinococcosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Novel isoguanine derivative of unlocked nucleic acid-Investigations of thermodynamics and biological potential of modified thrombin binding aptamer.

PubMed

Kotkowiak, Weronika; Czapik, Tomasz; Pasternak, Anna

2018-01-01

Thrombin binding aptamer (TBA), is a short DNA 15-mer that forms G-quadruplex structure and possesses anticoagulant properties. Some chemical modifications, including unlocked nucleic acids (UNA), 2'-deoxy-isoguanosine and 2'-deoxy-4-thiouridine were previously found to enhance the biological activity of TBA. In this paper, we present thermodynamic and biological characteristics of TBA variants that have been modified with novel isoguanine derivative of UNA as well as isoguanosine. Additionally, UNA-4-thiouracil and 4-thiouridine were also introduced simultaneously with isoguanine derivatives. Thermodynamic analysis indicates that the presence of isoguanosine in UNA or RNA series significantly decreases the stability of G-quadruplex structure. The highest destabilization is observed for substitution at one of the G-tetrad position. Addition of 4-thiouridine in UNA or RNA series usually decreases the unfavorable energetic cost of the presence of UNA or RNA isoguanine. Circular dichroism and thermal denaturation spectra in connection with thrombin time assay indicate that the introduction of UNA-isoguanine or isoguanosine into TBA negatively affects G-quadruplex folding and TBA anticoagulant properties. These findings demonstrate that the highly-ordered structure of TBA is essential for inhibition of thrombin activity.

Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

PubMed

Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

2014-01-01

The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

Virtual screening applications: a study of ligand-based methods and different structure representations in four different scenarios.

PubMed

Hristozov, Dimitar P; Oprea, Tudor I; Gasteiger, Johann

2007-01-01

Four different ligand-based virtual screening scenarios are studied: (1) prioritizing compounds for subsequent high-throughput screening (HTS); (2) selecting a predefined (small) number of potentially active compounds from a large chemical database; (3) assessing the probability that a given structure will exhibit a given activity; (4) selecting the most active structure(s) for a biological assay. Each of the four scenarios is exemplified by performing retrospective ligand-based virtual screening for eight different biological targets using two large databases--MDDR and WOMBAT. A comparison between the chemical spaces covered by these two databases is presented. The performance of two techniques for ligand--based virtual screening--similarity search with subsequent data fusion (SSDF) and novelty detection with Self-Organizing Maps (ndSOM) is investigated. Three different structure representations--2,048-dimensional Daylight fingerprints, topological autocorrelation weighted by atomic physicochemical properties (sigma electronegativity, polarizability, partial charge, and identity) and radial distribution functions weighted by the same atomic physicochemical properties--are compared. Both methods were found applicable in scenario one. The similarity search was found to perform slightly better in scenario two while the SOM novelty detection is preferred in scenario three. No method/descriptor combination achieved significant success in scenario four.

3-D QSARS FOR RANKING AND PRIORITIZATION OF LARGE CHEMICAL DATASETS: AN EDC CASE STUDY

EPA Science Inventory

The COmmon REactivity Pattern (COREPA) approach is a three-dimensional structure activity (3-D QSAR) technique that permits identification and quantification of specific global and local steroelectronic characteristics associated with a chemical's biological activity. It goes bey...

Design and synthesis of tetraol derivatives of 1,12-dicarba-closo-dodecaborane as non-secosteroidal vitamin D analogs.

PubMed

Fujii, Shinya; Kano, Atsushi; Masuno, Hiroyuki; Songkram, Chalermkiat; Kawachi, Emiko; Hirano, Tomoya; Tanatani, Aya; Kagechika, Hiroyuki

2014-09-15

Vitamin D receptor (VDR), a nuclear receptor for 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3, 1), is a promising target for multiple clinical applications. We recently developed non-secosteroidal VDR ligands based on a carbon-containing boron cluster, 1,12-dicarba-closo-dodecaborane (p-carborane), and examined the binding of one of them to VDR by means of crystallographic analysis. Here, we utilized that X-ray structure to design novel p-carborane-based tetraol-type vitamin D analogs, and we examined the biological activities of the synthesized compounds. Structure-activity relationship study revealed that introduction of an ω-hydroxyalkoxy functionality enhanced the biological activity, and the configuration of the substituent significantly influenced the potency. Among the synthesized compounds, 4-hydroxybutoxy derivative 9a exhibited the most potent activity, which was equal to that of the secosteroidal vitamin D analog, 19-nor-1α,25-dihydroxyvitamin D3 (2). Copyright © 2014 Elsevier Ltd. All rights reserved.

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects

PubMed Central

Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom “yun zhi”, Trametes versicolor, traditionally used for (cit.) “replenish essence and qi (vital energy)”. Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied. PMID:28829786

Tramesan, a novel polysaccharide from Trametes versicolor. Structural characterization and biological effects.

PubMed

Scarpari, Marzia; Reverberi, Massimo; Parroni, Alessia; Scala, Valeria; Fanelli, Corrado; Pietricola, Chiara; Zjalic, Slaven; Maresca, Vittoria; Tafuri, Agostino; Ricciardi, Maria R; Licchetta, Roberto; Mirabilii, Simone; Sveronis, Aris; Cescutti, Paola; Rizzo, Roberto

2017-01-01

Mushrooms represent a formidable source of bioactive compounds. Some of these may be considered as biological response modifiers; these include compounds with a specific biological function: antibiotics (e.g. plectasin), immune system stimulator (e,g, lentinan), antitumor agents (e.g. krestin, PSK) and hypolipidemic agents (e.g. lovastatin) inter alia. In this study, we focused on the Chinese medicinal mushroom "yun zhi", Trametes versicolor, traditionally used for (cit.) "replenish essence and qi (vital energy)". Previous studies indicated the potential activity of extracts from culture filtrate of asexual mycelia of T. versicolor in controlling the growth and secondary metabolism (e.g. mycotoxins) of plant pathogenic fungi. The quest of active principles produced by T. versicolor, allowed us characterising an exo-polysaccharide released in its culture filtrate and naming it Tramesan. Herein we evaluate the biological activity of Tramesan in different organisms: plants, mammals and plant pathogenic fungi. We suggest that the bioactivity of Tramesan relies mostly on its ability to act as pro antioxidant molecule regardless the biological system on which it was applied.

An undergraduate laboratory activity on molecular dynamics simulations.

PubMed

Spitznagel, Benjamin; Pritchett, Paige R; Messina, Troy C; Goadrich, Mark; Rodriguez, Juan

2016-01-01

Vision and Change [AAAS, 2011] outlines a blueprint for modernizing biology education by addressing conceptual understanding of key concepts, such as the relationship between structure and function. The document also highlights skills necessary for student success in 21st century Biology, such as the use of modeling and simulation. Here we describe a laboratory activity that allows students to investigate the dynamic nature of protein structure and function through the use of a modeling technique known as molecular dynamics (MD). The activity takes place over two lab periods that are 3 hr each. The first lab period unpacks the basic approach behind MD simulations, beginning with the kinematic equations that all bioscience students learn in an introductory physics course. During this period students are taught rudimentary programming skills in Python while guided through simple modeling exercises that lead up to the simulation of the motion of a single atom. In the second lab period students extend concepts learned in the first period to develop skills in the use of expert MD software. Here students simulate and analyze changes in protein conformation resulting from temperature change, solvation, and phosphorylation. The article will describe how these activities can be carried out using free software packages, including Abalone and VMD/NAMD. © 2016 The International Union of Biochemistry and Molecular Biology.

A Native Threonine Coordinates Ordered Water to Tune Light-Oxygen-Voltage (LOV) Domain Photocycle Kinetics and Osmotic Stress Signaling in Trichoderma reesei ENVOY.

PubMed

Lokhandwala, Jameela; Silverman Y de la Vega, Rafael I; Hopkins, Hilary C; Britton, Collin W; Rodriguez-Iglesias, Aroa; Bogomolni, Roberto; Schmoll, Monika; Zoltowski, Brian D

2016-07-08

Light-oxygen-voltage (LOV) domain-containing proteins function as small light-activated modules capable of imparting blue light control of biological processes. Their small modular nature has made them model proteins for allosteric signal transduction and optogenetic devices. Despite intense research, key aspects of their signal transduction mechanisms and photochemistry remain poorly understood. In particular, ordered water has been identified as a possible key mediator of photocycle kinetics, despite the lack of ordered water in the LOV active site. Herein, we use recent crystal structures of a fungal LOV protein ENVOY to interrogate the role of Thr(101) in recruiting water to the flavin active site where it can function as an intrinsic base to accelerate photocycle kinetics. Kinetic and molecular dynamic simulations confirm a role in solvent recruitment to the active site and identify structural changes that correlate with solvent recruitment. In vivo analysis of T101I indicates a direct role of the Thr(101) position in mediating adaptation to osmotic stress, thereby verifying biological relevance of ordered water in LOV signaling. The combined studies identify position 101 as a mediator of both allostery and photocycle catalysis that can impact organism physiology. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Inositolphosphoglycan mediators structurally related to glycosyl phosphatidylinositol anchors: synthesis, structure and biological activity.

PubMed

Martín-Lomas, M; Khiar, N; García, S; Koessler, J L; Nieto, P M; Rademacher, T W

2000-10-02

The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.

Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

PubMed

Hou, Jin-Jun; Shen, Yao; Yang, Zhou; Fang, Lin; Cai, Lu-Ying; Yao, Shuai; Long, Hua-Li; Wu, Wan-Ying; Guo, De-An

2017-10-01

Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC 50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Guaiacol peroxidase zymography for the undergraduate laboratory.

PubMed

Wilkesman, Jeff; Castro, Diana; Contreras, Lellys M; Kurz, Liliana

2014-01-01

This laboratory exercise presents a novel way to introduce undergraduate students to the specific detection of enzymatic activity by electrophoresis. First, students prepare a crude peroxidase extract and then analyze the homogenate via electrophoresis. Zymography, that is, a SDS-PAGE method to detect enzyme activity, is used to specifically detect peroxidase activity and furthermore, to analyze the total protein profile. After the assay, students may estimate the apparent molecular mass of the enzyme and discuss its structure. After the 4-h experiment, students gain knowledge concerning biological sample preparation, gel preparation, electrophoresis, and the importance of specific staining procedures for the detection of enzymatic activity. Copyright © 2014 The International Union of Biochemistry and Molecular Biology.

Activity of alkaloids on peptic ulcer: what's new?

PubMed

do Nascimento, Raphaela Francelino; de Sales, Igor Rafael Praxedes; de Oliveira Formiga, Rodrigo; Barbosa-Filho, José Maria; Sobral, Marianna Vieira; Tavares, Josean Fechine; Diniz, Margareth de Fátima Formiga Melo; Batista, Leônia Maria

2015-01-08

Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies.

Structural and functional studies on urease from pigeon pea (Cajanus cajan).

PubMed

Balasubramanian, Anuradha; Durairajpandian, Vishnuprabu; Elumalai, Sagadevan; Mathivanan, Narayanasamy; Munirajan, Arasambattu Kannan; Ponnuraj, Karthe

2013-07-01

Urease is an enzyme that catalyzes the hydrolysis of urea, forming ammonia and carbon dioxide, and is found in plants, microorganisms and invertebrates. Although plant and bacterial ureases are closely related at amino acid and at the structural level, the insecticidal activity is seen only in the plant ureases. In contrast, both plant and bacterial ureases exhibit antifungal activity. These two biological properties are independent of its ureolytic activity. However, till date the mechanism(s) behind the insecticidal and fungicidal activity of ureases are not clearly understood. Here we report the crystal structure of pigeon pea urease (PPU, Cajanus cajan) which is the second structure from the plant source. We have deduced the amino acid sequence of PPU and also report here studies on its stability, insecticidal and antifungal activity. PPU exhibits cellulase activity. Based on the structural analysis of PPU and docking studies with cellopentoase we propose a possible mechanism of antifungal activity of urease. Copyright © 2013 Elsevier B.V. All rights reserved.

Primary Molecular Disorders and Secondary Biological Adaptations in Bartter Syndrome

PubMed Central

Deschênes, Georges; Fila, Marc

2011-01-01

Bartter syndrome is a hereditary disorder that has been characterized by the association of hypokalemia, alkalosis, and the hypertrophy of the juxtaglomerular complex with secondary hyperaldosteronism and normal blood pressure. By contrast, the genetic causes of Bartter syndrome primarily affect molecular structures directly involved in the sodium reabsorption at the level of the Henle loop. The ensuing urinary sodium wasting and chronic sodium depletion are responsible for the contraction of the extracellular volume, the activation of the renin-aldosterone axis, the secretion of prostaglandins, and the biological adaptations of downstream tubular segments, meaning the distal convoluted tubule and the collecting duct. These secondary biological adaptations lead to hypokalemia and alkalosis, illustrating a close integration of the solutes regulation in the tubular structures. PMID:21941653

Close the Textbook & Open "The Cell: An Image Library"

ERIC Educational Resources Information Center

Saunders, Cheston; Taylor, Amy

2014-01-01

Many students leave the biology classroom with misconceptions centered on cellular structure. This article presents an activity in which students utilize images from an online database called "The Cell: An Image Library" (http://www.cellimagelibrary. org/) to gain a greater understanding of the diversity of cellular structure and the…

Fostering Today What Is Needed Tomorrow: Investigating Students' Interest in Science

ERIC Educational Resources Information Center

Blankenburg, Janet Susan; Höffler, Tim Niclas; Parchmann, Ilka

2016-01-01

This paper investigates the structure of German sixth-grade students' interest in science (N = 474; age 11-12 years) by considering different subject-related contexts (biology, chemistry, and physics) and different activities. Confirmatory factor analysis models were designed to validate the hypothetical structure of interest, connecting the whole…

Investigation of the Enzymes Involved in Lantibiotic Biosynthesis: Lacticin 481 and Haloduracin

ERIC Educational Resources Information Center

Ihnken, Leigh Anne Furgerson

2009-01-01

Lantibiotics are cyclic peptides that exhibit a range of biological properties, including antimicrobial activity. They are ribosomally-synthesized as linear precursor peptides that consist of two regions, an N-terminal leader peptide and a C-terminal propeptide (or structural) region. The structural region undergoes extensive enzyme-catalyzed…

Experimental and Theoretical Approaches for the Surface Interaction between Copper and Activated Sludge Microorganisms at Molecular Scale

NASA Astrophysics Data System (ADS)

Luo, Hong-Wei; Chen, Jie-Jie; Sheng, Guo-Ping; Su, Ji-Hu; Wei, Shi-Qiang; Yu, Han-Qing

2014-11-01

Interactions between metals and activated sludge microorganisms substantially affect the speciation, immobilization, transport, and bioavailability of trace heavy metals in biological wastewater treatment plants. In this study, the interaction of Cu(II), a typical heavy metal, onto activated sludge microorganisms was studied in-depth using a multi-technique approach. The complexing structure of Cu(II) on microbial surface was revealed by X-ray absorption fine structure (XAFS) and electron paramagnetic resonance (EPR) analysis. EPR spectra indicated that Cu(II) was held in inner-sphere surface complexes of octahedral coordination with tetragonal distortion of axial elongation. XAFS analysis further suggested that the surface complexation between Cu(II) and microbial cells was the distorted inner-sphere coordinated octahedra containing four short equatorial bonds and two elongated axial bonds. To further validate the results obtained from the XAFS and EPR analysis, density functional theory calculations were carried out to explore the structural geometry of the Cu complexes. These results are useful to better understand the speciation, immobilization, transport, and bioavailability of metals in biological wastewater treatment plants.

Computer-Aided Drug Design Methods.

PubMed

Yu, Wenbo; MacKerell, Alexander D

2017-01-01

Computational approaches are useful tools to interpret and guide experiments to expedite the antibiotic drug design process. Structure-based drug design (SBDD) and ligand-based drug design (LBDD) are the two general types of computer-aided drug design (CADD) approaches in existence. SBDD methods analyze macromolecular target 3-dimensional structural information, typically of proteins or RNA, to identify key sites and interactions that are important for their respective biological functions. Such information can then be utilized to design antibiotic drugs that can compete with essential interactions involving the target and thus interrupt the biological pathways essential for survival of the microorganism(s). LBDD methods focus on known antibiotic ligands for a target to establish a relationship between their physiochemical properties and antibiotic activities, referred to as a structure-activity relationship (SAR), information that can be used for optimization of known drugs or guide the design of new drugs with improved activity. In this chapter, standard CADD protocols for both SBDD and LBDD will be presented with a special focus on methodologies and targets routinely studied in our laboratory for antibiotic drug discoveries.

Savinin, a lignan from Pterocarpus santalinus inhibits tumor necrosis factor-alpha production and T cell proliferation.

PubMed

Cho, J Y; Park, J; Kim, P S; Yoo, E S; Baik, K U; Park, M H

2001-02-01

Two lignans were isolated from the heartwood of Pterocarpus santalinus by activity-guided fractionation and investigated for their biological properties and molecular mechanism of action. On the basis of their spectroscopic data, these compounds were identified as savinin (1) and calocedrin (2), dibenzyl butyrolactone-type lignan compounds having an alpha-arylidene gamma-lactone structure. These lignans significantly inhibited tumor necrosis factor (TNF)-a production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and T cell proliferation elicited by concanavalin (Con A), without displaying cytotoxicity. The molecular inhibitory mechanism of compound 1 was confirmed to be mediated by the non-polar butyrolactone ring, according to a structure-relationship study with structurally related and unrelated compounds, such as arctigenin (a dibenzyl butyrolactone type lignan), eudesmin (a furofuran type lignan), isolariciresinol (a dibenzylbutane type lignan), and cynaropicrin (a sesquiterpene lactone). The results suggest that savinin may act as an active principle in the reported biological activities of P. santalinus, such as antiinflammatory effect, by mediation of the butyrolactone ring as a valuable pharmacophore.

HomoSAR: bridging comparative protein modeling with quantitative structural activity relationship to design new peptides.

PubMed

Borkar, Mahesh R; Pissurlenkar, Raghuvir R S; Coutinho, Evans C

2013-11-15

Peptides play significant roles in the biological world. To optimize activity for a specific therapeutic target, peptide library synthesis is inevitable; which is a time consuming and expensive. Computational approaches provide a promising way to simply elucidate the structural basis in the design of new peptides. Earlier, we proposed a novel methodology termed HomoSAR to gain insight into the structure activity relationships underlying peptides. Based on an integrated approach, HomoSAR uses the principles of homology modeling in conjunction with the quantitative structural activity relationship formalism to predict and design new peptide sequences with the optimum activity. In the present study, we establish that the HomoSAR methodology can be universally applied to all classes of peptides irrespective of sequence length by studying HomoSAR on three peptide datasets viz., angiotensin-converting enzyme inhibitory peptides, CAMEL-s antibiotic peptides, and hAmphiphysin-1 SH3 domain binding peptides, using a set of descriptors related to the hydrophobic, steric, and electronic properties of the 20 natural amino acids. Models generated for all three datasets have statistically significant correlation coefficients (r(2)) and predictive r2 (r(pred)2) and cross validated coefficient ( q(LOO)2). The daintiness of this technique lies in its simplicity and ability to extract all the information contained in the peptides to elucidate the underlying structure activity relationships. The difficulties of correlating both sequence diversity and variation in length of the peptides with their biological activity can be addressed. The study has been able to identify the preferred or detrimental nature of amino acids at specific positions in the peptide sequences. Copyright © 2013 Wiley Periodicals, Inc.

Biological capacitance studies of anodes in microbial fuel cells using electrochemical impedance spectroscopy.

PubMed

Lu, Zhihao; Girguis, Peter; Liang, Peng; Shi, Haifeng; Huang, Guangtuan; Cai, Lankun; Zhang, Lehua

2015-07-01

It is known that cell potential increases while anode resistance decreases during the start-up of microbial fuel cells (MFCs). Biological capacitance, defined as the apparent capacitance attributed to biological activity including biofilm production, plays a role in this phenomenon. In this research, electrochemical impedance spectroscopy was employed to study anode capacitance and resistance during the start-up period of MFCs so that the role of biological capacitance was revealed in electricity generation by MFCs. It was observed that the anode capacitance ranged from 3.29 to 120 mF which increased by 16.8% to 18-20 times over 10-12 days. Notably, lowering the temperature and arresting biological activity via fixation by 4% para formaldehyde resulted in the decrease of biological capacitance by 16.9 and 62.6%, indicating a negative correlation between anode capacitance and anode resistance of MFCs. Thus, biological capacitance of anode should play an important role in power generation by MFCs. We suggest that MFCs are not only biological reactors and/or electrochemical cells, but also biological capacitors, extending the vision on mechanism exploration of electron transfer, reactor structure design and electrode materials development of MFCs.

Pharmaceutically active secondary metabolites of marine actinobacteria.

PubMed

Manivasagan, Panchanathan; Venkatesan, Jayachandran; Sivakumar, Kannan; Kim, Se-Kwon

2014-04-01

Marine actinobacteria are one of the most efficient groups of secondary metabolite producers and are very important from an industrial point of view. Many representatives of the order Actinomycetales are prolific producers of thousands of biologically active secondary metabolites. Actinobacteria from terrestrial sources have been studied and screened since the 1950s, for many important antibiotics, anticancer, antitumor and immunosuppressive agents. However, frequent rediscovery of the same compounds from the terrestrial actinobacteria has made them less attractive for screening programs in the recent years. At the same time, actinobacteria isolated from the marine environment have currently received considerable attention due to the structural diversity and unique biological activities of their secondary metabolites. They are efficient producers of new secondary metabolites that show a range of biological activities including antibacterial, antifungal, anticancer, antitumor, cytotoxic, cytostatic, anti-inflammatory, anti-parasitic, anti-malaria, antiviral, antioxidant, anti-angiogenesis, etc. In this review, an evaluation is made on the current status of research on marine actinobacteria yielding pharmaceutically active secondary metabolites. Bioactive compounds from marine actinobacteria possess distinct chemical structures that may form the basis for synthesis of new drugs that could be used to combat resistant pathogens. With the increasing advancement in science and technology, there would be a greater demand for new bioactive compounds synthesized by actinobacteria from various marine sources in future. Copyright © 2013 Elsevier GmbH. All rights reserved.

An integrated cell-free metabolic platform for protein production and synthetic biology

PubMed Central

Jewett, Michael C; Calhoun, Kara A; Voloshin, Alexei; Wuu, Jessica J; Swartz, James R

2008-01-01

Cell-free systems offer a unique platform for expanding the capabilities of natural biological systems for useful purposes, i.e. synthetic biology. They reduce complexity, remove structural barriers, and do not require the maintenance of cell viability. Cell-free systems, however, have been limited by their inability to co-activate multiple biochemical networks in a single integrated platform. Here, we report the assessment of biochemical reactions in an Escherichia coli cell-free platform designed to activate natural metabolism, the Cytomim system. We reveal that central catabolism, oxidative phosphorylation, and protein synthesis can be co-activated in a single reaction system. Never before have these complex systems been shown to be simultaneously activated without living cells. The Cytomim system therefore promises to provide the metabolic foundation for diverse ab initio cell-free synthetic biology projects. In addition, we describe an improved Cytomim system with enhanced protein synthesis yields (up to 1200 mg/l in 2 h) and lower costs to facilitate production of protein therapeutics and biochemicals that are difficult to make in vivo because of their toxicity, complexity, or unusual cofactor requirements. PMID:18854819

Signal transduction networks and the biology of plant cells.

PubMed

Chrispeels, M J; Holuigue, L; Latorre, R; Luan, S; Orellana, A; Peña-Cortes, H; Raikhel, N V; Ronald, P C; Trewavas, A

1999-01-01

The development of plant transformation in the mid-1980s and of many new tools for cell biology, molecular genetics, and biochemistry has resulted in enormous progress in plant biology in the past decade. With the completion of the genome sequence of Arabidopsis thaliana just around the corner, we can expect even faster progress in the next decade. The interface between cell biology and signal transduction is emerging as a new and important field of research. In the past we thought of cell biology strictly in terms of organelles and their biogenesis and function, and researchers focused on questions such as, how do proteins enter chloroplasts? or, what is the structure of the macromolecules of the cell wall and how are these molecules secreted? Signal transduction dealt primarily with the perception of light (photomorphogenesis) or hormones and with the effect such signals have on enhancing the activity of specific genes. Now we see that the fields of cell biology and signal transduction are merging because signals pass between organelles and a single signal transduction pathway usually involves multiple organelles or cellular structures. Here are some examples to illustrate this new paradigm. How does abscisic acid (ABA) regulate stomatal closure? This pathway involves not only ABA receptors whose location is not yet known, but cation and anion channels in the plasma membrane, changes in the cytoskeleton, movement of water through water channels in the tonoplast and the plasma membrane, proteins with a farnesyl tail that can be located either in the cytosol or attached to a membrane, and probably unidentified ion channels in the tonoplast. In addition there are highly localized calcium oscillations in the cytoplasm resulting from the release of calcium stored in various compartments. The activities of all these cellular structures need to be coordinated during ABA-induced stomatal closure. For another example of the interplay between the proteins of signal transduction pathways and cytoplasmic structures, consider how plants mount defense responses against pathogens. Elicitors produced by pathogens bind to receptors on the plant plasma membrane or in the cytosol and eventually activate a large number of genes. This results in the coordination of activities at the plasma membrane (production of reactive oxygen species), in the cytoskeleton, localized calcium oscillations, and the modulation of protein kinases and protein phosphatases whose locations remain to be determined. The movement of transcription factors into the nucleus to activate the defense genes requires their release from cytosolic anchors and passage through the nuclear pore complexes of the nuclear envelope. This review does not cover all the recent progress in plant signal transduction and cell biology; it is confined to the topics that were discussed at a recent (November 1998) workshop held in Santiago at which lecturers from Chile, the USA and the UK presented recent results from their laboratories.

Improving protein delivery of fibroblast growth factor-2 from bacterial inclusion bodies used as cell culture substrates.

PubMed

Seras-Franzoso, Joaquin; Peebo, Karl; García-Fruitós, Elena; Vázquez, Esther; Rinas, Ursula; Villaverde, Antonio

2014-03-01

Bacterial inclusion bodies (IBs) have recently been used to generate biocompatible cell culture interfaces, with diverse effects on cultured cells such as cell adhesion enhancement, stimulation of cell growth or induction of mesenchymal stem cell differentiation. Additionally, novel applications of IBs as sustained protein delivery systems with potential applications in regenerative medicine have been successfully explored. In this scenario, with IBs gaining significance in the biomedical field, the fine tuning of this functional biomaterial is crucial. In this work, the effect of temperature on fibroblast growth factor-2 (FGF-2) IB production and performance has been evaluated. FGF-2 was overexpressed in Escherichia coli at 25 and 37 °C, producing IBs with differences in size, particle structure and biological activity. Cell culture topographies made with FGF-2 IBs biofabricated at 25 °C showed higher levels of biological activity as well as a looser supramolecular structure, enabling a higher protein release from the particles. In addition, the controlled use of FGF-2 protein particles enabled the generation of functional topographies with multiple biological activities being effective on diverse cell types. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

THE FUTURE OF TOXICOLOGY-PREDICTIVE TOXICOLOGY ...

EPA Pesticide Factsheets

A chemistry approach to predictive toxicology relies on structure−activity relationship (SAR) modeling to predict biological activity from chemical structure. Such approaches have proven capabilities when applied to well-defined toxicity end points or regions of chemical space. These approaches are less well-suited, however, to the challenges of global toxicity prediction, i.e., to predicting the potential toxicity of structurally diverse chemicals across a wide range of end points of regulatory and pharmaceutical concern. New approaches that have the potential to significantly improve capabilities in predictive toxicology are elaborating the “activity” portion of the SAR paradigm. Recent advances in two areas of endeavor are particularly promising. Toxicity data informatics relies on standardized data schema, developed for particular areas of toxicological study, to facilitate data integration and enable relational exploration and mining of data across both historical and new areas of toxicological investigation. Bioassay profiling refers to large-scale high-throughput screening approaches that use chemicals as probes to broadly characterize biological response space, extending the concept of chemical “properties” to the biological activity domain. The effective capture and representation of legacy and new toxicity data into mineable form and the large-scale generation of new bioassay data in relation to chemical toxicity, both employing chemical stru

Cyclic Dipeptides: Secondary Metabolites Isolated from Different Microorganisms with Diverse Biological Activities.

PubMed

Ortiz, Aurelio; Sansinenea, Estibaliz

2017-01-01

Cyclic dipeptides are the simplest peptide derivatives commonly found in nature. These chiral molecules are easily synthesized from readily available α-amino acids using a simple methodology. They are privileged structures with the ability to bind to a wide range of receptors and have a broad variety of biological and pharmacological activities. We will give a brief overview of their status giving and interesting reference list about the last works. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Division of Biological and Medical Research research summary 1984-1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barr, S.H.

1985-08-01

The Division of Biological and Medical Research at Argonne National Laboratory conducts multidisciplinary research aimed at defining the biological and medical hazards to man from energy technologies and new energy options. These technically oriented studies have a strong base in fundamental research in a variety of scientific disciplines, including molecular and cellular biology, biophysics, genetics, radiobiology, pharmacology, biochemistry, chemistry, environmental toxicology, and epidemiology. This research summary is organized into six parts. The first five parts reflect the Divisional structure and contain the scientific program chapters, which summarize the activities of the individual groups during the calendar year 1984 and themore » first half of 1985. To provide better continuity and perspective, previous work is sometimes briefly described. Although the summaries are short, efforts have been made to indicate the range of research activities for each group.« less

Academe and the Threat of Biological Terrorism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atlas, Ronald M.; Weller, Richard E.

1999-04-03

A legally binding protocol to monitor compliance with Biological and Toxin Weapons Convention (BWC) could have a substantial impact on academia. This is because of the large number of academic sites, and the complexity of activities and business relationships found in academia. Several hundred academic institutions could be required to file declarations, depending upon the specific''triggers'' adopted by the Ad Hoc Group to the BWC. Activities at academic sites that might''trigger'' a requirement for declaration include: biological defense, working with listed agents or toxins, production capacity, biopesticide research, vaccine production, high (BL3) biological containment, and aerobiology. The management structure ofmore » academic institutions will make it difficult for them to scrupulously comply with declaration requirements. A major educational program will be required to ensure academic compliance with any mandatory measures adopted to strengthen the BWC.« less

S28 peptidases: lessons from a seemingly 'dysfunctional' family of two.

PubMed

Kozarich, John W

2010-06-28

A recent paper in BMC Structural Biology reports the crystal structure of human prolylcarboxypeptidase (PRCP), one of the two members of the S28 peptidase family. Comparison of the substrate-binding site of PRCP with that of its family partner, dipeptidyl dipeptidase 7 (DPP7), helps to explain the different enzymatic activities of these structurally similar proteins, and also reveals a novel apparent charge-relay system in PRCP involving the active-site catalytic histidine. See research article: http://www.biomedcentral.com/1472-6807/10/16/

Automatic knowledge extraction from chemical structures: the case of mutagenicity prediction.

PubMed

Ferrari, T; Cattaneo, D; Gini, G; Golbamaki Bakhtyari, N; Manganaro, A; Benfenati, E

2013-01-01

This work proposes a new structure-activity relationship (SAR) approach to mine molecular fragments that act as structural alerts for biological activity. The entire process is designed to fit with human reasoning, not only to make the predictions more reliable but also to permit clear control by the user in order to meet customized requirements. This approach has been tested on the mutagenicity endpoint, showing marked prediction skills and, more interestingly, bringing to the surface much of the knowledge already collected in the literature as well as new evidence.

[BIOLOGICAL ACTIVITY OF ANTIMICROBIAL PEPTIDES FROM CHICKENS THROMBOCYTES].

PubMed

Sycheva, M V; Vasilchenko, A S; Rogozhin, E A; Pashkova, T M; Popova, L P; Kartashova, O L

2016-01-01

Isolation and study of biological activity of antimicrobial peptides from chickens thrombocytes. Peptides from chickens thrombocytes, obtained by reverse-phase high-performance liquid chromatography method with stepped and linear gradients of concentration increase of the organic solvent were used in the study. Their antimicrobial activity was determined by microtitration method in broth; mechanism of biological effect--by using fluorescent spectroscopy method with DNA-tropic dyes. Individual fractions of peptides were isolated from chickens thrombocytes, that possess antimicrobial activity against Staphylococcus aureus P209 and Escherichia coli K12. A disruption of integrity of barrier structures of microorganisms under the effect of thrombocyte antimicrobial peptides and predominance of cells with damaged membrane in the population of E. coli was established. The data obtained on antimicrobial activity and mechanism of bactericidal effect of the peptide fractions from chickens thrombocytes isolated for the first time expand the understanding of functional properties of chickens thrombocytes and open a perspective for their further study with the aim of use as antimicrobial means.

Isolation, structures, and structure - cytotoxic activity relationships of withanolides and physalins from Physalis angulata.

PubMed

Damu, Amooru G; Kuo, Ping-Chung; Su, Chung-Ren; Kuo, Tsung-Hsiao; Chen, Tzu-Hsuan; Bastow, Kenneth F; Lee, Kuo-Hsiung; Wu, Tian-Shung

2007-07-01

Phytochemical investigation of Physalis angulata was initiated following primary biological screening. Fractionation of CHCl3 and n-BuOH solubles of the MeOH extract from the whole plant was guided by in vitro cytotoxic activity assay using cultured HONE-1 and NUGC cells and led to the isolation of seven new withanolides, withangulatins B-H (1-7), and a new minor physalin, physalin W (8), along with 14 known compounds, including physaprun A, withaphysanolide, dihydrowithanolide E, physanolide A, withaphysalin A, and physalins B, D, F, G, I, J, T, U, and V. New compounds (1-8) were fully characterized by a combination of spectroscopic methods (1D and 2D NMR and MS) and the relative stereochemical assignments based on NOESY correlations and analysis of coupling constants. Biological evaluation of these compounds against a panel of human cancer cell lines showed broad cytotoxic activity. Withangulatin B (1) and physalins D (10) and F (11) displayed potent cytotoxic activity against a panel of human cancer cell lines with EC50 values ranging from 0.2 to 1.6 microg/mL. Structure-activity relationship analysis indicated that withanolides and physalins with 4beta-hydroxy-2-en-1-one and 5beta,6beta-epoxy moieties are potential cytotoxic agents.

Antimalarial activity of synthetic 1,2,4-trioxanes and cyclic peroxy ketals, a quantum similarity study

NASA Astrophysics Data System (ADS)

Gironés, X.; Gallegos, A.; Carbó-Dorca, R.

2001-12-01

In this work, the antimalarial activity of two series of 20 and 7 synthetic 1,2,4-trioxanes and a set of 20 cyclic peroxy ketals are tested for correlation search by means of Molecular Quantum Similarity Measures (MQSM). QSAR models, dealing with different biological responses (IC90, IC50 and ED90) of the parasite Plasmodium Falciparum, are constructed using MQSM as molecular descriptors and are satisfactorily correlated. The statistical results of the 20 1,2,4-trioxanes are deeply analyzed to elucidate the relevant structural features in the biological activity, revealing the importance of phenyl substitutions.

Glycolipids from seaweeds and their potential biotechnological applications.

PubMed

Plouguerné, Erwan; da Gama, Bernardo A P; Pereira, Renato C; Barreto-Bergter, Eliana

2014-01-01

Marine macroalgae, or seaweeds, are a formidable source of natural compounds with diverse biological activities. In the last five decades it has been estimated that more than 3000 natural compounds were discovered from these organisms. The great majority of the published works have focused on terpenoids. In comparison, glycolipids are a neglected class of macroalgal secondary metabolites therefore remaining as a largely unknown reservoir of molecular diversity. Nevertheless, the interest regarding these compounds has been growing fast in the last decades as activities of ecological or pharmaceutical interest have been highlighted. This paper will review recent work regarding isolation and structural characterization of glycolipids from seaweeds and their prospective biological activities.

A biologically active fructan from the roots of Arctium lappa L., var. Herkules.

PubMed

Kardosová, A; Ebringerová, A; Alföldi, J; Nosál'ová, G; Franová, S; Hríbalová, V

2003-11-01

From the roots of Arctium lappa L., var. Herkules a low-molecular-weight fructofuranan of the inulin-type has been isolated by water extraction and ethanol precipitation, followed by ion-exchange chromatography and gel filtration of the crude precipitate. The methods employed in structural determination were methylation analysis and 1H and 13C NMR spectral measurements. In tests for antitussive activity in cats the fructan was found to be equally active as some non-narcotic, synthetic preparations used in clinical practice to treat coughing, and in mitogenic and comitogenic tests its biological response was comparable to that of the commercial Zymosan immunomodulator.

Teaching structure: student use of software tools for understanding macromolecular structure in an undergraduate biochemistry course.

PubMed

Jaswal, Sheila S; O'Hara, Patricia B; Williamson, Patrick L; Springer, Amy L

2013-01-01

Because understanding the structure of biological macromolecules is critical to understanding their function, students of biochemistry should become familiar not only with viewing, but also with generating and manipulating structural representations. We report a strategy from a one-semester undergraduate biochemistry course to integrate use of structural representation tools into both laboratory and homework activities. First, early in the course we introduce the use of readily available open-source software for visualizing protein structure, coincident with modules on amino acid and peptide bond properties. Second, we use these same software tools in lectures and incorporate images and other structure representations in homework tasks. Third, we require a capstone project in which teams of students examine a protein-nucleic acid complex and then use the software tools to illustrate for their classmates the salient features of the structure, relating how the structure helps explain biological function. To ensure engagement with a range of software and database features, we generated a detailed template file that can be used to explore any structure, and that guides students through specific applications of many of the software tools. In presentations, students demonstrate that they are successfully interpreting structural information, and using representations to illustrate particular points relevant to function. Thus, over the semester students integrate information about structural features of biological macromolecules into the larger discussion of the chemical basis of function. Together these assignments provide an accessible introduction to structural representation tools, allowing students to add these methods to their biochemical toolboxes early in their scientific development. © 2013 by The International Union of Biochemistry and Molecular Biology.

Temporal change in biological community structure in the Fountain Creek basin, Colorado, 2001-2008

USGS Publications Warehouse

Zuellig, Robert E.; Bruce, James F.; Stogner, Sr., Robert W.

2010-01-01

In 2001, the U.S. Geological Survey, in cooperation with Colorado Springs City Engineering, began a study to better understand the relations between environmental characteristics and biological communities in the Fountain Creek basin in order to aide water-resource management and guide future monitoring activities. To accomplish this task, environmental (streamflow, habitat, and water chemistry) and biological (fish and macroinvertebrate) data were collected annually at 24 sites over a 6- or 8-year period (fish, 2003 to 2008; macroinvertebrates, 2001 to 2008). For this report, these data were first analyzed to determine the presence of temporal change in macroinvertebrate and fish community structure among years using nonparametric multivariate statistics. Where temporal change in the biological communities was found, these data were further analyzed using additional nonparametric multivariate techniques to determine which subset of selected streamflow, habitat, or water-chemistry variables best described site-specific changes in community structure relative to a gradient of urbanization. This study identified significant directional patterns of temporal change in macroinvertebrate and fish community structure at 15 of 24 sites in the Fountain Creek basin. At four of these sites, changes in environmental variables were significantly correlated with the concurrent temporal change identified in macroinvertebrate and fish community structure (Monument Creek above Woodmen Road at Colorado Springs, Colo.; Monument Creek at Bijou Street at Colorado Springs, Colo.; Bear Creek near Colorado Springs, Colo.; Fountain Creek at Security, Colo.). Combinations of environmental variables describing directional temporal change in the biota appeared to be site specific as no single variable dominated the results; however, substrate composition variables (percent substrate composition composed of sand, gravel, or cobble) collectively were present in 80 percent of the environmental variable subsets that were significantly correlated with temporal change in the macroinvertebrate and fish community structure. Other important environmental variables related to temporal change in the biological community structure included those describing channel form (streambank height) and streamflow (normalized annual mean daily flow, high flood-pulse count). Site-specific results from this study were derived from a relatively small number of observations (6 or 8 years of data); therefore, additional years of data may reveal other sites with temporal change in biological community structure, or could define stronger and more consistent linkages between environmental variables and observed temporal change. Likewise current variable subsets could become weaker. Nonetheless, there were several sites where temporal change was detected in this study that could not be explained by the available environmental variables studied herein. Modification of current data-collection activities may be necessary to better understand site-specific temporal relations between biological communities and environmental variables.

Advances in the Biology and Chemistry of Sialic Acids

PubMed Central

Chen, Xi; Varki, Ajit

2010-01-01

Sialic acids are a subset of nonulosonic acids, which are nine-carbon alpha-keto aldonic acids. Natural existing sialic acid-containing structures are presented in different sialic acid forms, various sialyl linkages, and on diverse underlying glycans. They play important roles in biological, pathological, and immunological processes. Sialobiology has been a challenging and yet attractive research area. Recent advances in chemical and chemoenzymatic synthesis as well as large-scale E. coli cell-based production have provided a large library of sialoside standards and derivatives in amounts sufficient for structure-activity relationship studies. Sialoglycan microarrays provide an efficient platform for quick identification of preferred ligands for sialic acid-binding proteins. Future research on sialic acid will continue to be at the interface of chemistry and biology. Research efforts will not only lead to a better understanding of the biological and pathological importance of sialic acids and their diversity, but could also lead to the development of therapeutics. PMID:20020717

Design of synthetic biological logic circuits based on evolutionary algorithm.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

2013-08-01

The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

Generation of 3D templates of active sites of proteins with rigid prosthetic groups.

PubMed

Nebel, Jean-Christophe

2006-05-15

With the increasing availability of protein structures, the generation of biologically meaningful 3D patterns from the simultaneous alignment of several protein structures is an exciting prospect: active sites could be better understood, protein functions and protein 3D structures could be predicted more accurately. Although patterns can already be generated at the fold and topological levels, no system produces high-resolution 3D patterns including atom and cavity positions. To address this challenge, our research focuses on generating patterns from proteins with rigid prosthetic groups. Since these groups are key elements of protein active sites, the generated 3D patterns are expected to be biologically meaningful. In this paper, we present a new approach which allows the generation of 3D patterns from proteins with rigid prosthetic groups. Using 237 protein chains representing proteins containing porphyrin rings, our method was validated by comparing 3D templates generated from homologues with the 3D structure of the proteins they model. Atom positions were predicted reliably: 93% of them had an accuracy of 1.00 A or less. Moreover, similar results were obtained regarding chemical group and cavity positions. Results also suggested our system could contribute to the validation of 3D protein models. Finally, a 3D template was generated for the active site of human cytochrome P450 CYP17, the 3D structure of which is unknown. Its analysis showed that it is biologically meaningful: our method detected the main patterns of the cytochrome P450 superfamily and the motifs linked to catalytic reactions. The 3D template also suggested the position of a residue, which could be involved in a hydrogen bond with CYP17 substrates and the shape and location of a cavity. Comparisons with independently generated 3D models comforted these hypotheses. Alignment software (Nestor3D) is available at http://www.kingston.ac.uk/~ku33185/Nestor3D.html

RNA polymerase pausing and nascent RNA structure formation are linked through clamp domain movement

PubMed Central

Hein, Pyae P.; Kolb, Kellie E.; Windgassen, Tricia; Bellecourt, Michael J.; Darst, Seth A.; Mooney, Rachel A.; Landick, Robert

2014-01-01

The rates of RNA synthesis and nascent RNA folding into biologically active structures are linked via pausing by RNA polymerase (RNAP). Structures that form within the RNA exit channel can increase pausing by interacting with bacterial RNAP or decrease pausing by preventing backtracking. Conversely, pausing is required for proper folding of some RNAs. Opening of the RNAP clamp domain is proposed to mediate some effects of nascent RNA structures. However, the connections among RNA structure formation, clamp movement, and catalytic activity remain uncertain. We assayed exit-channel structure formation in Escherichia coli RNAP together with disulfide crosslinks that favor closed or open clamp conformations and found that clamp position directly influences RNA structure formation and catalytic activity. We report that exit-channel RNA structures slow pause escape by favoring clamp opening and through interactions with the flap that slow translocation. PMID:25108353

Bio-inspired fabrication of stimuli-responsive photonic crystals with hierarchical structures and their applications

NASA Astrophysics Data System (ADS)

Lu, Tao; Peng, Wenhong; Zhu, Shenmin; Zhang, Di

2016-03-01

When the constitutive materials of photonic crystals (PCs) are stimuli-responsive, the resultant PCs exhibit optical properties that can be tuned by the stimuli. This can be exploited for promising applications in colour displays, biological and chemical sensors, inks and paints, and many optically active components. However, the preparation of the required photonic structures is the first issue to be solved. In the past two decades, approaches such as microfabrication and self-assembly have been developed to incorporate stimuli-responsive materials into existing periodic structures for the fabrication of PCs, either as the initial building blocks or as the surrounding matrix. Generally, the materials that respond to thermal, pH, chemical, optical, electrical, or magnetic stimuli are either soft or aggregate, which is why the manufacture of three-dimensional hierarchical photonic structures with responsive properties is a great challenge. Recently, inspired by biological PCs in nature which exhibit both flexible and responsive properties, researchers have developed various methods to synthesize metals and metal oxides with hierarchical structures by using a biological PC as the template. This review will focus on the recent developments in this field. In particular, PCs with biological hierarchical structures that can be tuned by external stimuli have recently been successfully fabricated. These findings offer innovative insights into the design of responsive PCs and should be of great importance for future applications of these materials.

Early, structured disease modifying anti-rheumatic drug (DMARD) therapy reduces cardiovascular risk in rheumatoid arthritis--a single centre study using non-biologic drugs.

PubMed

Chatterjee, Sumit; Sarkate, Pankaj; Ghosh, Sudip; Biswas, Monodeep; Ghosh, Alakendu

2013-08-01

Rheumatoid arthritis, being a chronic disease requires long-term management of patients with drugs. The increasing cost of biologics in this era of disease management led us to devise a treatment regime, optimal for use in a developing country like India, which was economical as well as effective in controlling disease activity. To investigate if combination therapy with DMARDs can reduce cardiovascular risk in early Rheumatoid Arthritis, besides controlling disease activity. A small cohort of early Rheumatoid subjects with disease duration less than 1 year were treated with a structured DMARD regime and were followed up over a year. Disease activity score, C-reactive protein (CRP) and cardiac risk markers like lipid panel and carotid intima-medial thickness were monitored at 6 months and 1 year. A significant reduction (p < 0.001) of disease activity as well as cardiac risk parameters were observed. Our study showed that treatment of early rheumatoid arthritis with a combination regime of traditional DMARDs is highly effective in controlling disease activity as well as cardiovascular risk.

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

Ring-substituted 4-hydroxy-1H-quinolin-2-ones: preparation and biological activity.

PubMed

Jampilek, Josef; Musiol, Robert; Pesko, Matus; Kralova, Katarina; Vejsova, Marcela; Carroll, James; Coffey, Aidan; Finster, Jacek; Tabak, Dominik; Niedbala, Halina; Kozik, Violetta; Polanski, Jaroslaw; Csollei, Jozef; Dohnal, Jiri

2009-03-13

In the study, a series of twelve ring-substituted 4-hydroxy-1H-quinolin-2-one derivatives were prepared. The procedures for synthesis of the compounds are presented. The compounds were analyzed using RP-HPLC to determine lipophilicity and tested for their photosynthesis-inhibiting activity using spinach (Spinacia oleracea L.) chloroplasts. All the synthesized compounds were also evaluated for antifungal activity using in vitro screening with eight fungal strains. For all the compounds, the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed, as well as their structure-activity relationships (SAR).

In Vitro Antioxidant Activity of Selected 4-Hydroxy-chromene-2-one Derivatives—SAR, QSAR and DFT Studies

PubMed Central

Mladenović, Milan; Mihailović, Mirjana; Bogojević, Desanka; Matić, Sanja; Nićiforović, Neda; Mihailović, Vladimir; Vuković, Nenad; Sukdolak, Slobodan; Solujić, Slavica

2011-01-01

The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro. PMID:21686153

Integrative Approaches for Predicting in vivo Effects of Chemicals from their Structural Descriptors and the Results of Short-term Biological Assays

PubMed Central

Low, Yen S.; Sedykh, Alexander; Rusyn, Ivan; Tropsha, Alexander

2017-01-01

Cheminformatics approaches such as Quantitative Structure Activity Relationship (QSAR) modeling have been used traditionally for predicting chemical toxicity. In recent years, high throughput biological assays have been increasingly employed to elucidate mechanisms of chemical toxicity and predict toxic effects of chemicals in vivo. The data generated in such assays can be considered as biological descriptors of chemicals that can be combined with molecular descriptors and employed in QSAR modeling to improve the accuracy of toxicity prediction. In this review, we discuss several approaches for integrating chemical and biological data for predicting biological effects of chemicals in vivo and compare their performance across several data sets. We conclude that while no method consistently shows superior performance, the integrative approaches rank consistently among the best yet offer enriched interpretation of models over those built with either chemical or biological data alone. We discuss the outlook for such interdisciplinary methods and offer recommendations to further improve the accuracy and interpretability of computational models that predict chemical toxicity. PMID:24805064

Structural and chemical aspects of HPMA copolymers as drug carriers.

PubMed

Ulbrich, Karel; Subr, Vladimír

2010-02-17

Synthetic strategies and chemical and structural aspects of the synthesis of HPMA copolymer conjugates with various drugs and other biologically active molecules are described and discussed in this chapter. The discussion is held from the viewpoint of design and structure of the polymer backbone and biodegradable spacer between a polymer and drug, structure and methods of attachment of the employed drugs to the carrier and structure and methods of conjugation with targeting moieties. Physicochemical properties of the water-soluble polymer-drug conjugates and polymer micelles including mechanisms of drug release are also discussed. Detailed description of biological behavior of the polymer-drug conjugates as well as application of the copolymers for surface modification and targeting of gene delivery vectors are not included, they are presented and discussed in separate chapters of this issue. Copyright 2009 Elsevier B.V. All rights reserved.

Anacardic Acid Constituents from Cashew Nut Shell Liquid: NMR Characterization and the Effect of Unsaturation on Its Biological Activities

PubMed Central

Morais, Selene M.; Silva, Katherine A.; Araujo, Halisson; Vieira, Icaro G.P.; Alves, Daniela R.; Fontenelle, Raquel O.S.; Silva, Artur M.S.

2017-01-01

Anacardic acids are the main constituents of natural cashew nut shell liquid (CNSL), obtained via the extraction of cashew shells with hexane at room temperature. This raw material presents high technological potential due to its various biological properties. The main components of CNSL are the anacardic acids, salicylic acid derivatives presenting a side chain of fifteen carbon atoms with different degrees of unsaturation (monoene–15:1, diene–15:2, and triene–15:3). Each constituent was isolated by column chromatography using silica gel impregnated with silver nitrate. The structures of the compounds were characterized by nuclear magnetic resonance through complete and unequivocal proton and carbon assignments. The effect of the side chain unsaturation was also evaluated in relation to antioxidant, antifungal and anticholinesterase activities, and toxicity against Artemia salina. The triene anacardic acid provided better results in antioxidant activity assessed by the inhibition of the free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH), higher cytotoxicity against A. salina, and acetylcholinesterase (AChE) inhibition. Thus, increasing the unsaturation of the side chain of anacardic acid increases its action against free radicals, AChE enzyme, and A. salina nauplii. In relation to antifungal activity, an inverse result was obtained, and the linearity of the molecule plays an important role, with monoene being the most active. In conclusion, the changes in structure of anacardic acids, which cause differences in polarity, contribute to the increase or decrease in the biological activity assessed. PMID:28300791

Physicochemical and biological characterization of SB2, a biosimilar of Remicade® (infliximab)

PubMed Central

Hong, Juyong; Lee, Yuhwa; Lee, Changsoo; Eo, Suhyeon; Kim, Soyeon; Park, Seungkyu; Seo, Donghyuck; Lee, Youngji; Yeon, Soojeong; Bou-Assaf, George; Sosic, Zoran; Zhang, Wei

2017-01-01

ABSTRACT A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor–α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy. PMID:28005456

Delta sleep-inducing peptide (DSIP): a still unresolved riddle.

PubMed

Kovalzon, Vladimir M; Strekalova, Tatyana V

2006-04-01

Delta sleep-inducing peptide (DSIP) was isolated from rabbit cerebral venous blood by Schoenenberger-Monnier group from Basel in 1977 and initially regarded as a candidate sleep-promoting factor. However, the link between DSIP and sleep has never been further characterized, in part because of the lack of isolation of the DSIP gene, protein and possible related receptor. Thus the hypothesis regarding DSIP as a sleep factor is extremely poorly documented and still weak. Although DSIP itself presented a focus of study for a number of researchers, its natural occurrence and biological activity still remains obscure. DSIP structure is different from any other known representative of the various peptide families. In this mini-review we hypothesize the existence of a DSIP-like peptide(s) that is responsible (at least partly) for DSIP-like immunoreactivity and DSIP biological activity. This assumption is based on: (i) a highly specific distribution of DSIP-like immunoreactivity in the neurosecretory hypothalamic nuclei of various vertebrate species that are not particularly relevant for sleep regulation, as revealed by the histochemical studies of the Geneva group (Charnay et al.); (ii) a large spectrum of DSIP biological activity revealed by biochemical and physiological studies in vitro; (iii) significant slow-wave sleep (SWS) promoting activity of certain artificial DSIP structural analogues (but not DSIP itself!) in rabbits and rats revealed by our early studies; and (iv) significant SWS-promoting activity of a naturally occurring dermorphin-decapeptide that is structurally similar to DSIP (in five of the nine positions) and the sleep-suppressing effect of its optical isomer, as revealed in rabbits. Potential future studies are outlined, including natural synthesis and release of this DSIP-like peptide and its role in neuroendocrine regulation.

Visualization of molecular structures using HoloLens-based augmented reality

PubMed Central

Hoffman, MA; Provance, JB

2017-01-01

Biological molecules and biologically active small molecules are complex three dimensional structures. Current flat screen monitors are limited in their ability to convey the full three dimensional characteristics of these molecules. Augmented reality devices, including the Microsoft HoloLens, offer an immersive platform to change how we interact with molecular visualizations. We describe a process to incorporate the three dimensional structures of small molecules and complex proteins into the Microsoft HoloLens using aspirin and the human leukocyte antigen (HLA) as examples. Small molecular structures can be introduced into the HoloStudio application, which provides native support for rotating, resizing and performing other interactions with these molecules. Larger molecules can be imported through the Unity gaming development platform and then Microsoft Visual Developer. The processes described here can be modified to import a wide variety of molecular structures into augmented reality systems and improve our comprehension of complex structural features. PMID:28815109

Using NMR chemical shifts to calculate the propensity for structural order and disorder in proteins.

PubMed

Tamiola, Kamil; Mulder, Frans A A

2012-10-01

NMR spectroscopy offers the unique possibility to relate the structural propensities of disordered proteins and loop segments of folded peptides to biological function and aggregation behaviour. Backbone chemical shifts are ideally suited for this task, provided that appropriate reference data are available and idiosyncratic sensitivity of backbone chemical shifts to structural information is treated in a sensible manner. In the present paper, we describe methods to detect structural protein changes from chemical shifts, and present an online tool [ncSPC (neighbour-corrected Structural Propensity Calculator)], which unites aspects of several current approaches. Examples of structural propensity calculations are given for two well-characterized systems, namely the binding of α-synuclein to micelles and light activation of photoactive yellow protein. These examples spotlight the great power of NMR chemical shift analysis for the quantitative assessment of protein disorder at the atomic level, and further our understanding of biologically important problems.

The effects of a visualization-centered curriculum on conceptual understanding and representational competence in high school biology

NASA Astrophysics Data System (ADS)

Wilder, Anna

The purpose of this study was to investigate the effects of a visualization-centered curriculum, Hemoglobin: A Case of Double Identity, on conceptual understanding and representational competence in high school biology. Sixty-nine students enrolled in three sections of freshman biology taught by the same teacher participated in this study. Online Chemscape Chime computer-based molecular visualizations were incorporated into the 10-week curriculum to introduce students to fundamental structure and function relationships. Measures used in this study included a Hemoglobin Structure and Function Test, Mental Imagery Questionnaire, Exam Difficulty Survey, the Student Assessment of Learning Gains, the Group Assessment of Logical Thinking, the Attitude Toward Science in School Assessment, audiotapes of student interviews, students' artifacts, weekly unit activity surveys, informal researcher observations and a teacher's weekly questionnaire. The Hemoglobin Structure and Function Test, consisting of Parts A and B, was administered as a pre and posttest. Part A used exclusively verbal test items to measure conceptual understanding, while Part B used visual-verbal test items to measure conceptual understanding and representational competence. Results of the Hemoglobin Structure and Function pre and posttest revealed statistically significant gains in conceptual understanding and representational competence, suggesting the visualization-centered curriculum implemented in this study was effective in supporting positive learning outcomes. The large positive correlation between posttest results on Part A, comprised of all-verbal test items, and Part B, using visual-verbal test items, suggests this curriculum supported students' mutual development of conceptual understanding and representational competence. Evidence based on student interviews, Student Assessment of Learning Gains ratings and weekly activity surveys indicated positive attitudes toward the use of Chemscape Chime software and the computer-based molecular visualization activities as learning tools. Evidence from these same sources also indicated that students felt computer-based molecular visualization activities in conjunction with other classroom activities supported their learning. Implications for instructional design are discussed.

Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology.

PubMed

Hu, Jianwen; Han, Jizhong; Li, Haoran; Zhang, Xian; Liu, Lan Lan; Chen, Fei; Zeng, Bin

2018-01-01

Mammalian cells, e.g., CHO, BHK, HEK293, HT-1080, and NS0 cells, represent important manufacturing platforms in bioengineering. They are widely used for the production of recombinant therapeutic proteins, vaccines, anticancer agents, and other clinically relevant drugs. HEK293 (human embryonic kidney 293) cells and their derived cell lines provide an attractive heterologous system for the development of recombinant proteins or adenovirus productions, not least due to their human-like posttranslational modification of protein molecules to provide the desired biological activity. Secondly, they also exhibit high transfection efficiency yielding high-quality recombinant proteins. They are easy to maintain and express with high fidelity membrane proteins, such as ion channels and transporters, and thus are attractive for structural biology and electrophysiology studies. In this article, we review the literature on HEK293 cells regarding their origins but also stress their advancements into the different cell lines engineered and discuss some significant aspects which make them versatile systems for biopharmaceutical manufacturing, drug screening, structural biology research, and electrophysiology applications. © 2018 S. Karger AG, Basel.

Using an FPLC to Promote Active Learning of the Principles of Protein Structure and Purification

ERIC Educational Resources Information Center

Robinson, Rebekah L.; Neely, Amy E.; Mojadedi, Wais; Threatt, Katie N.; Davis, Nicole Y.; Weiland, Mitch H.

2017-01-01

The concepts of protein purification are often taught in undergraduate biology and biochemistry lectures and reinforced during laboratory exercises; however, very few reported activities allow students to directly gain experience using modern protein purification instruments, such as Fast Protein Liquid Chromatography (FPLC). This laboratory…

Isolation, NMR studies, and biological activities of onopordopicrin from Centaurea sonchifolia.

PubMed

Lonergan, G; Routsi, E; Georgiadis, T; Agelis, G; Hondrelis, J; Matsoukas, J; Larsen, L K; Caplan, F R

1992-02-01

A sesquiterpene lactone, onopordopicrin [1], has been isolated from Centaurea sonchifolia. Its structure was established by 2D nmr (1H-1H and 13C-1H correlations), and the conformation in CHCl3 was examined by nOe studies. Cytotoxic, antibacterial, and antifungal activities are reported.

New biologically active epidioxysterols from Stereum hirsutum.

PubMed

Cateni, Francesca; Doljak, Bojan; Zacchigna, Marina; Anderluh, Marko; Piltaver, Andrej; Scialino, Giuditta; Banfi, Elena

2007-11-15

From the fungus Stereum hirsutum have been isolated and identified two new epidioxysterols 1, 4, together with two known ones 2 and 3. Their structures were elucidated on the basis of spectroscopic analysis and chemical reactions. Epidioxysterols 1-4 have been shown to possess a significant activity against Mycobacterium tuberculosis.

Insights into animal and plant lectins with antimicrobial activities.

PubMed

Dias, Renata de Oliveira; Machado, Leandro Dos Santos; Migliolo, Ludovico; Franco, Octavio Luiz

2015-01-05

Lectins are multivalent proteins with the ability to recognize and bind diverse carbohydrate structures. The glyco -binding and diverse molecular structures observed in these protein classes make them a large and heterogeneous group with a wide range of biological activities in microorganisms, animals and plants. Lectins from plants and animals are commonly used in direct defense against pathogens and in immune regulation. This review focuses on sources of animal and plant lectins, describing their functional classification and tridimensional structures, relating these properties with biotechnological purposes, including antimicrobial activities. In summary, this work focuses on structural-functional elucidation of diverse lectin groups, shedding some light on host-pathogen interactions; it also examines their emergence as biotechnological tools through gene manipulation and development of new drugs.

Processing of natural and recombinant CXCR3-targeting chemokines and implications for biological activity.

PubMed

Hensbergen, P J; van der Raaij-Helmer, E M; Dijkman, R; van der Schors, R C; Werner-Felmayer, G; Boorsma, D M; Scheper, R J; Willemze, R; Tensen, C P

2001-09-01

Chemokines comprise a class of peptides with chemotactic activity towards leukocytes. The potency of different chemokines for the same receptor often varies as a result of differences in primary structure. In addition, post-translational modifications have been shown to affect the effectiveness of chemokines. Although in several studies, natural CXCR3-targeting chemokines have been isolated, detailed information about the proteins and their possible modifications is lacking. Using a combination of liquid chromatography and mass spectrometry we studied the protein profile of CXCR3-targeting chemokines expressed by interferon-gamma-stimulated human keratinocytes. The biological implications of one of the identified modifications was studied in more detail using calcium mobilization and chemotaxis assays. We found that the primary structure of human CXCL10 is different from the generally accepted sequence. In addition we identified a C-terminally truncated CXCL10, lacking the last four amino acids. Native CXCL11 was primarily found in its intact mature form but we also found a mass corresponding to an N-terminally truncated human CXCL11, lacking the first two amino acids FP, indicating that this chemokine is a substrate for dipeptidylpeptidase IV. Interestingly, this same truncation was found when we expressed human CXCL11 in Drosophila S2 cells. The biological activity of this truncated form of CXCL11 was greatly reduced, both in calcium mobilization (using CXCR3 expressing CHO cells) as well as its chemotactic activity for CXCR3-expressing T-cells. It is concluded that detailed information on chemokines at the protein level is important to characterize the exact profile of these chemotactic peptides as modifications can severely alter their biological activity.

Action of plant proteinase inhibitors on enzymes of physiopathological importance.

PubMed

Oliva, Maria Luiza V; Sampaio, Misako U

2009-09-01

Obtained from leguminous seeds, various plant proteins inhibit animal proteinases, including human, and can be considered for the development of compounds with biological activity. Inhibitors from the Bowman-Birk and plant Kunitz-type family have been characterized by proteinase specificity, primary structure and reactive site. Our group mostly studies the genus Bauhinia, mainly the species bauhinioides, rufa, ungulata and variegata. In some species, more than one inhibitor was characterized, exhibiting different properties. Although proteins from this group share high structural similarity, they present differences in proteinase inhibition, explored in studies using diverse biological models.

Aminooxylated Carbohydrates: Synthesis and Applications.

PubMed

Pifferi, Carlo; Daskhan, Gour Chand; Fiore, Michele; Shiao, Tze Chieh; Roy, René; Renaudet, Olivier

2017-08-09

Among other classes of biomolecules, carbohydrates and glycoconjugates are widely involved in numerous biological functions. In addition to addressing the related synthetic challenges, glycochemists have invested intense efforts in providing access to structures that can be used to study, activate, or inhibit these biological processes. Over the past few decades, aminooxylated carbohydrates have been found to be key building blocks for achieving these goals. This review provides the first in-depth overview covering several aspects related to the syntheses and applications of aminooxylated carbohydrates. After a brief introduction to oxime bonds and their relative stabilities compared to related C═N functions, synthetic aspects of oxime ligation and methodologies for introducing the aminooxy functionality onto both glycofuranosyls and glycopyranosyls are described. The subsequent section focuses on biological applications involving aminooxylated carbohydrates as components for the construcion of diverse architectures. Mimetics of natural structures represent useful tools for better understanding the features that drive carbohydrate-receptor interaction, their biological output and they also represent interesting structures with improved stability and tunable properties. In the next section, multivalent structures such as glycoclusters and glycodendrimers obtained through oxime ligation are described in terms of synthetic design and their biological applications such as immunomodulators. The second-to-last section discusses miscellaneous applications of oxime-based glycoconjugates, such as enantioselective catalysis and glycosylated oligonucleotides, and conclusions and perspectives are provided in the last section.

Biologically Inspired Micro-Flight Research

NASA Technical Reports Server (NTRS)

Raney, David L.; Waszak, Martin R.

2003-01-01

Natural fliers demonstrate a diverse array of flight capabilities, many of which are poorly understood. NASA has established a research project to explore and exploit flight technologies inspired by biological systems. One part of this project focuses on dynamic modeling and control of micro aerial vehicles that incorporate flexible wing structures inspired by natural fliers such as insects, hummingbirds and bats. With a vast number of potential civil and military applications, micro aerial vehicles represent an emerging sector of the aerospace market. This paper describes an ongoing research activity in which mechanization and control concepts for biologically inspired micro aerial vehicles are being explored. Research activities focusing on a flexible fixed- wing micro aerial vehicle design and a flapping-based micro aerial vehicle concept are presented.

Evaluation of Teachers' Activities in the Use of Animated Instructional Resource Materials in Biology Teaching in Senior Secondary Schools in Bauchi State Nigeria

ERIC Educational Resources Information Center

Kwasu, I. A.; Abubakar; Ema, E.

2015-01-01

This paper presents a profile on how teachers in senior secondary schools in Bauchi state Nigeria utilise animated instructional resource (AIR) in the teaching of biology. A structured questionnaire used to generate data on the availability, accessibility and application of the AIR for classroom instruction by teachers. The instrument for data…

NASA Space Biology Program. Eighth annual symposium's program and abstracts

NASA Technical Reports Server (NTRS)

Halstead, T. W. (Editor)

1984-01-01

The activities included five half days of presentations by space biology principal investigators, an evening of poster session presentations by research associates, and an afternoon session devoted to the Flight Experiments Program. Areas of discussion included the following: gravity receptor mechanisms; physiological effects of gravity, structural mass; fluid dynamics and metabolism; mechanisms of plant response; and the role of gravity in development.

Carbocyclic nucleoside analogues: classification, target enzymes, mechanisms of action and synthesis

NASA Astrophysics Data System (ADS)

Matyugina, E. S.; Khandazhinskaya, A. P.; Kochetkov, Sergei N.

2012-08-01

Key biological targets (S-adenosyl-L-homocysteine hydrolase, telomerase, human immunodeficiency virus reverse transcriptase, herpes virus DNA polymerase and hepatitis B virus DNA polymerase) and the mechanisms of action of carbocyclic nucleoside analogues are considered. Structural types of analogues are discussed. Methods of synthesis for the most promising compounds and the spectrum of their biological activities are described. The bibliography includes 126 references.

Could LogP be a principal determinant of biological activity in 18-crown-6 ethers? Synthesis of biologically active adamantane-substituted diaza-crowns.

PubMed

Supek, Fran; Ramljak, Tatjana Šumanovac; Marjanović, Marko; Buljubašić, Maja; Kragol, Goran; Ilić, Nataša; Smuc, Tomislav; Zahradka, Davor; Mlinarić-Majerski, Kata; Kralj, Marijeta

2011-08-01

18-crown-6 ethers are known to exert their biological activity by transporting K(+) ions across cell membranes. Using non-linear Support Vector Machines regression, we searched for structural features that influence antiproliferative activity in a diverse set of 19 known oxa-, monoaza- and diaza-18-crown-6 ethers. Here, we show that the logP of the molecule is the most important molecular descriptor, among ∼1300 tested descriptors, in determining biological potency (R(2)(cv) = 0.704). The optimal logP was at 5.5 (Ghose-Crippen ALOGP estimate) while both higher and lower values were detrimental to biological potency. After controlling for logP, we found that the antiproliferative activity of the molecule was generally not affected by side chain length, molecular symmetry, or presence of side chain amide links. To validate this QSAR model, we synthesized six novel, highly lipophilic diaza-18-crown-6 derivatives with adamantane moieties attached to the side arms. These compounds have near-optimal logP values and consequently exhibit strong growth inhibition in various human cancer cell lines and a bacterial system. The bioactivities of different diaza-18-crown-6 analogs in Bacillus subtilis and cancer cells were correlated, suggesting conserved molecular features may be mediating the cytotoxic response. We conclude that relying primarily on the logP is a sensible strategy in preparing future 18-crown-6 analogs with optimized biological activity. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Formulation, Quality Control and Safety Issues of Nanocarriers Used for Cancer Treatment.

PubMed

Bianco, Ismael D; Ceballos, Marcelo R; Casado, Cristian; Dabbene, Viviana G; Rizzi, Carolina; Mizutamari, R Kiyomi

2017-01-01

Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few. In this context, nanotechnology with the emerging tools of nanoengineering offers many possibilities to guide the design of new products with improved safety and efficacy. The presence of several reacting groups and the sensitivity of their properties to small changes in composition make nanocarriers tunable not only to modify their stability in a particular environment but also to respond to changes in biological situations in the right place and time frame. This review summarizes the main preparation methods and formulation strategies of nano and microcarriers designed for drug delivery applications for cancer treatment and will attempt to give a glimpse on how their structure, shape, physico-chemical properties and chemical composition may affect their overall stability and interactions with biological systems. We will also cover aspects of nanoengineering that are opening new opportunities for the development of more effective nanomedicines, emphasizing on the challenges that have to be kept in mind when dealing with biological activities of nanocarriers that depend not only on their chemical composition but also on those of the structures formed by them and by their interactions with biological systems. From this, a very important issue that emerges is that nanocarriers frequently display an intrinsic bioactivity (i.e.: immunomodulatory). Therefore, it should be stressed that nanocarriers cannot be considered as inert, biocompatible excipients. Furthermore, their biological activity will mostly depend on the physical and chemical properties of the structures of the nanoparticles that are presented to living systems. As an approach to the rational design of new pharmaceutical products, nanoengineering is providing new tools for the precise control of the properties of nanocarriers for cancer treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Using Concrete & Representational Experiences to Understand the Structure of DNA: A Four-Step Instructional Framework

ERIC Educational Resources Information Center

Harrell, Pamela Esprivalo; Richards, Debbie; Collins, James; Taylor, Sarah

2005-01-01

A description of learning experience that uses a four-step instrumentational framework involving concrete and representational experiences to promote conceptual understanding of abstract biological concepts by a series of closely-related activities is presented. The students are introduced to the structure and implications of DNA using four…

Mutagen Structure and Transcriptional Response: Induction of Distinct Transcriptional Profiles in Salmonella TA100 by the Drinking-Water Mutagen MX and Its Homologues

EPA Science Inventory

The relationship between chemical structure and biological activity has been examined for various compounds and endpoints for decades. To explore this question relative to global gene expression, we performed microarray analysis of Salmonella TA100 after treatment under condition...

Building scientific confidence in metabolic similarity in read-across through the use of in vitro, in silico and analytical data

EPA Science Inventory

The underlying principle of read-across is that the biological activity of a chemical is inherent in its molecular structure. Analogues are typically identified by structural similarity then evaluated on the basis of their bioavailability, reactivity and metabolic similarity. Whi...

20180312 - Building scientific confidence in metabolic similarity in read-across through the use of in vitro, in silico and analytical data (SOT)

EPA Science Inventory

The underlying principle of read-across is that the biological activity of a chemical is inherent in its molecular structure. Analogues are typically identified by structural similarity then evaluated on the basis of their bioavailability, reactivity and metabolic similarity. Whi...

Modifications of the chemical structure of phenolics differentially affect physiological activities in pulvinar cells of Mimosa pudica L. II. Influence of various molecular properties in relation to membrane transport.

PubMed

Rocher, Françoise; Roblin, Gabriel; Chollet, Jean-François

2017-03-01

Early prediction of compound absorption by cells is of considerable importance in the building of an integrated scheme describing the impact of a compound on intracellular biological processes. In this scope, we study the structure-activity relationships of several benzoic acid-related phenolics which are involved in many plant biological phenomena (growth, flowering, allelopathy, defense processes). Using the partial least squares (PLS) regression method, the impact of molecular descriptors that have been shown to play an important role concerning the uptake of pharmacologically active compounds by animal cells was analyzed in terms of the modification of membrane potential, variations in proton flux, and inhibition of the osmocontractile reaction of pulvinar cells of Mimosa pudica leaves. The hydrogen bond donors (HBD) and hydrogen bond acceptors (HBA), polar surface area (PSA), halogen ratio (Hal ratio), number of rotatable bonds (FRB), molar volume (MV), molecular weight (MW), and molar refractivity (MR) were considered in addition to two physicochemical properties (logD and the amount of non-dissociated form in relation to pKa). HBD + HBA and PSA predominantly impacted the three biological processes compared to the other descriptors. The coefficient of determination in the quantitative structure-activity relationship (QSAR) models indicated that a major part of the observed seismonasty inhibition and proton flux modification can be explained by the impact of these descriptors, whereas this was not the case for membrane potential variations. These results indicate that the transmembrane transport of the compounds is a predominant component. An increasing number of implicated descriptors as the biological processes become more complex may reflect their impacts on an increasing number of sites in the cell. The determination of the most efficient effectors may lead to a practical use to improve drugs in the control of microbial attacks on plants.

Tunable Shape-Shifting Structures for Military Applications

DTIC Science & Technology

2014-01-01

autonomous (also self - healing and fault-tolerant) systems that can provide multifunctionality whilst minimising weight/size, particularly in extreme...The proof-of-concept approach was successfully demonstrated. It is possible to deform the surface of a multilayer soft structure with a high level...biological systems found in Nature (e.g. adaptive skin texture of cephalopods), active soft structures producing large deformations offer attractive ways to

Prediction of p38 map kinase inhibitory activity of 3, 4-dihydropyrido [3, 2-d] pyrimidone derivatives using an expert system based on principal component analysis and least square support vector machine

PubMed Central

Shahlaei, M.; Saghaie, L.

2014-01-01

A quantitative structure–activity relationship (QSAR) study is suggested for the prediction of biological activity (pIC50) of 3, 4-dihydropyrido [3,2-d] pyrimidone derivatives as p38 inhibitors. Modeling of the biological activities of compounds of interest as a function of molecular structures was established by means of principal component analysis (PCA) and least square support vector machine (LS-SVM) methods. The results showed that the pIC50 values calculated by LS-SVM are in good agreement with the experimental data, and the performance of the LS-SVM regression model is superior to the PCA-based model. The developed LS-SVM model was applied for the prediction of the biological activities of pyrimidone derivatives, which were not in the modeling procedure. The resulted model showed high prediction ability with root mean square error of prediction of 0.460 for LS-SVM. The study provided a novel and effective approach for predicting biological activities of 3, 4-dihydropyrido [3,2-d] pyrimidone derivatives as p38 inhibitors and disclosed that LS-SVM can be used as a powerful chemometrics tool for QSAR studies. PMID:26339262

Light-Activated Content Release from Liposomes

PubMed Central

Leung, Sarah J.; Romanowski, Marek

2012-01-01

Successful integration of diagnostic and therapeutic actions at the level of individual cells requires new materials that combine biological compatibility with functional versatility. This review focuses on the development of liposome-based functional materials, where payload release is activated by light. Methods of sensitizing liposomes to light have progressed from the use of organic molecular moieties to the use of metallic plasmon resonant structures. This development has facilitated application of near infrared light for activation, which is preferred for its deep penetration and low phototoxicity in biological tissues. Presented mechanisms of light-activated liposomal content release enable precise in vitro manipulation of minute amounts of reagents, but their use in clinical diagnostic and therapeutic applications will require demonstration of safety and efficacy. PMID:23139729

Biological Activity Predictions and Hydrogen Bonding Analysis in Quinolines

NASA Astrophysics Data System (ADS)

Gupta, Palvi; Kamni

The paper has been designed to make a comprehensive review of a particular series of organic molecular assembly in the form of compendium. An overview of general description of fifteen quinoline derivatives has been given. The biological activity spectra of quinoline derivatives have been correlated on structure activity relationships base which provides the different Pa (possibility of activity) and Pi (possibility of inactivity) values. Expositions of the role of intermolecular interactions in the identified derivatives have been discussed with the standard distance and angle cut-off criteria criteria as proposed by Desiraju and Steiner (1999) in an International monogram on crystallography. Distance-angle scatter plots for intermolecular interactions are presented for a better understanding of the packing interactions which exist in quinoline derivatives.

The biophysical basis of Benveniste experiments: Entropy, structure, and information in water

NASA Astrophysics Data System (ADS)

Widom, Allan; Srivastava, Yogendra; Valenzi, Vincenzo

Benveniste had observed that highly dilute (and even in the absence of physical molecules) biological agents still triggered relevant biological systems. Some of these experiments were reproduced in three other laboratories who cosigned the article, (Davenas et al., Nature 1988, 333, 816). Further works, [(Medical Hypotheses 2000, 54, 33), (Rivista di Biologia/Biology Forum 97, 2004, 169)], showed that molecular activity in more than 50 biochemical systems and even in bacteria could be induced by electromagnetic signals transferred through water solutes. The sources of the electromagnetic signals were recordings of specific biological activities. These results suggest that electromagnetic transmission of biochemical information can be stored in the electric dipole moments of water in close analogy to the manner in which magnetic moments store information on a computer disk. The electromagnetic transmission would enable in vivo transmissions of the specific molecular information between two functional biomolecules. In the present work, the physical nature of such biological information storage and retrieval in ordered quantum electromagnetic domains of water will be discussed.

Novel pyrrolopyrimidines and triazolopyrrolopyrimidines carrying a biologically active sulfonamide moieties as anticancer agents.

PubMed

Ghorab, Mostafa M; Alsaisd, Mansour S; Nissan, Yassin M

2015-01-01

A new series of pyrroles 5, 6, pyrrolopyrimidines 8, 11-14, 16-29, triazolo-pyrrolopyrimidines 9, 10 and 15 carrying a biologically active sulfonamide moities were synthesized using 2-amino-3-cyano-4-(4-bromophenyl)pyrrole 5 as a strategic starting material. The structures of the prepared compounds were confirmed by elemental analyses, IR, 1H-NMR and 13C-NMR data. All of the synthesized compounds showed promising anticancer activity against breast cancer cell line (MCF7) compared to doxorubicin as reference drug, especially compounds 5-17, 21-24 and 28 with better IC50 than that of doxorubicin. In order to suggest the mechanism of action of their cytotoxic activities, molecular docking on the active site of c-Src was done and good results were obtained.

Report on maloine, a new alkaloid discovered from G. maloi: Structural characterization and biological activity

NASA Astrophysics Data System (ADS)

Çela, Dorisa; Nepravishta, Ridvan; Lazari, Diamanto; Gaziano, Roberta; Moroni, Gabriella; Pica, Francesca; Paci, Maurizio; Abazi, Sokol

2017-02-01

Gymnospermium maloi Kit Tan, & Shuka is a new endemic species of the genus Gymnospermium Spach which has been described recently from the southern part of Albania. The members of this genus are poorly studied for what it concern the secondary metabolites in general and the class of alkaloids in particular. In fact from Gymnospermium genus, there are only few alkaloids characterized, (namely albertramine, albertidine, and albertine) isolated from G. albertii. Until now the chemical composition and the structure elucidation of other possible secondary metabolites, especially alkaloids, remain largely unknown. Here we report, for the first time, the structure of a new alkaloid isolated from G. maloi, designated by us as maloine, and obtained by the use of 2D homonuclear and heteronuclear NMR spectroscopy, FTIR, UV, Fluorescence and HPLC/MS spectra. The biological activity of the crude extract of Gymnospermium maloi and of its alkaloid maloine, was evaluated in vitro on human chronic myeloid leukemia cell line K562 and results herewith reported.

Community Structure Analysis and Biodegradation Potential of Aniline-Degrading Bacteria in Biofilters.

PubMed

Hou, Luanfeng; Wu, Qingping; Gu, Qihui; Zhou, Qin; Zhang, Jumei

2018-07-01

Aniline has aroused general concern owing to its strong toxicity and widespread distribution in water and soil. In the present study, the bacterial community composition before and after aniline acclimation was investigated. High-throughput Illumina MiSeq sequencing analysis illustrated a large shift in the structure of the bacterial community during the aniline acclimation period. Bacillus, Lactococcus, and Enterococcus were the dominant bacteria in biologically activated carbon before acclimation. However, the proportions of Pseudomonas, Thermomonas, and Acinetobacter increased significantly and several new bacterial taxa appeared after aniline acclimation, indicating that aniline acclimation had a strong impact on the bacterial community structure of biological activated carbon samples. Strain AN-1 accounted for the highest number of colonies on incubation plates and was identified as Acinetobacter sp. according to phylogenetic analysis of the 16S ribosomal ribonucleic acid gene sequence. Strain AN-1 was able to grow on aniline at pH value 4.0-10.0 and showed high aniline-degrading ability at neutral pH.

Chitin and Chitosan Preparation from Marine Sources. Structure, Properties and Applications

PubMed Central

Younes, Islem; Rinaudo, Marguerite

2015-01-01

This review describes the most common methods for recovery of chitin from marine organisms. In depth, both enzymatic and chemical treatments for the step of deproteinization are compared, as well as different conditions for demineralization. The conditions of chitosan preparation are also discussed, since they significantly impact the synthesis of chitosan with varying degree of acetylation (DA) and molecular weight (MW). In addition, the main characterization techniques applied for chitin and chitosan are recalled, pointing out the role of their solubility in relation with the chemical structure (mainly the acetyl group distribution along the backbone). Biological activities are also presented, such as: antibacterial, antifungal, antitumor and antioxidant. Interestingly, the relationship between chemical structure and biological activity is demonstrated for chitosan molecules with different DA and MW and homogeneous distribution of acetyl groups for the first time. In the end, several selected pharmaceutical and biomedical applications are presented, in which chitin and chitosan are recognized as new biomaterials taking advantage of their biocompatibility and biodegradability. PMID:25738328

Design and synthesis of some new 2,3'-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents.

PubMed

Elzahhar, Perihan A; Elkazaz, Salwa; Soliman, Raafat; El-Tombary, Alaa A; Shaltout, Hossam A; El-Ashmawy, Ibrahim M; Abdel Wahab, Abeer E; El-Hawash, Soad A

2017-08-01

Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. This work describes synthesis of new series of 2,3'-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.

Synthesis, spectroscopic, DFT studies and biological activity of some ruthenium carbonyl derivatives of bis-(salicylaldehyde)phenylenediimine Schiff base ligand

NASA Astrophysics Data System (ADS)

Ramadan, Ramadan M.; Abu Al-Nasr, Ahmad K.; Ali, Omayma A. M.

2018-06-01

Bis-(salicylaldehyde)phenylenediimine Schiff base (H2salphen) reacted oxidatively with the triruthenium dodecacarbonyl complex, [Ru3(CO)12] to give the dicarbonyl derivative [Ru(CO)2(salphen)], 1. In presence of a secondary ligand L (L = pyridine, triphenyl phosphine, 2-aminobenzimidazole or thiourea), the monocarbonyl derivatives [Ru(CO)(salphen)L], 2-5, were isolated. When the bipyridine (bpy) ligand was used as a secondary ligand, the dicarbonyl complex [Ru(CO)2(Hsalphen)(bpy)], 6, was obtained. In complexes 1-5, the Schiff base ligand acted as a tetradentate, while it coordinated as a bidentate in complex 6. The structure and stoichiometry of the complexes were investigated by the conventional analytical and spectroscopic techniques, which revealed that they have several structural arrangements. The structures of ligand and complexes were verified by theoretical calculations based on accurate DFT approximations. The relative reactivities were estimated using chemical descriptors analysis. Biological activities of the complexes against the Escherchia coli and Staphylococcus aureus bacteria were screened.

Structure and biological activity of protopanaxatriol-type saponins from the roots of Panax notoginseng.

PubMed

Sun, Hongxiang; Yang, Zhigang; Ye, Yiping

2006-01-01

The further purification of the total saponins from the roots of Panax notoginseng by using ordinary and reversed-phase silica-gel, as well as Sephadex LH-20 chromatography afford seven adjuvant active protopanaxatriol-type saponins (PTS), ginsenosides-Rh1 (Rh1),-Rh4 (Rh4),-Rg1 (Rg1),-Re (Re), notoginsenosides-R1 (R1),-R2 (R2),-U (U). These saponins were evaluated for their haemolytic activities and adjuvant potentials on the cellular and humoral immune responses of ICR mice against ovalbumin (OVA). The effect of the substitution pattern of these PTS on their biological activities was investigated and structure-activity relationships were established. Among seven PTS, the haemolytic activity of Rh1 was higher than that of other six compounds (p<0.001) The HD50 values of Rh4 and U were significantly bigger than those of R2, Rg1 and Re (p<0.05 or p<0.01). Seven PTS could significantly increase the concanavalin A (Con A)-, lipopolysaccharide (LPS)- and OVA-induced splenocyte proliferation in the OVA-immunized mice (p<0.01 or p<0.001). The OVA-specific IgG, IgG1, IgG2a and IgG2b antibody levels in serum were also significantly enhanced by seven PTS compared with OVA control group (p<0.01 or p<0.001). The structure-activity relationship studies suggested that the number, the length and the position of sugar side chains, and the type of glucosyl group in the structure of PTS could not only affect their haemolytic activities and adjuvant potentials, but have significant effects on the nature of the immune responses. The information about this structure/function relationship might be useful for developing semisynthetic tetracyclic triterpenoid saponin derivatives with immunological adjuvant activity, as well as a reference to the distribution of the functional groups composing the saponin molecule.

Nitrogen-Containing Constituents of Black Cohosh: Chemistry, Structure Elucidation, and Biological Activities

PubMed Central

Lankin, David C.; Cisowska, Tamara; Chen, Shao-Nong; Pauli, Guido F.; van Breemen, Richard B.

2016-01-01

The roots/rhizomes of black cohosh (Actaea racemosa L. syn. Cimicifuga racemosa [L]. Nutt., Ranunculaceae) have been used traditionally by Native Americans to treat colds, rheumatism, and a variety of conditions related to women’s health. In recent years black cohosh preparations have become popular dietary supplements among women seeking alternative treatments for menopausal complaints. The popularity of the plant has led to extensive phytochemical and biological investigations, including several clinical trials. Most of the phytochemical and biological research has focused on two abundant classes of compounds: the triterpene glycosides and phenolic acids. A third group of phytoconstituents that has received far less attention consists of the alkaloids and related compounds that contain nitrogen. This chapter summarizes the current state of knowledge of the chemistry and biological activities associated with this group of constituents and provides some perspective on their significance for future research on this interesting plant. PMID:27795590

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides

PubMed Central

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-01-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. PMID:26747427

Comparison of biological activities of human antithrombins with high-mannose or complex-type nonfucosylated N-linked oligosaccharides.

PubMed

Yamada, Tsuyoshi; Kanda, Yutaka; Takayama, Makoto; Hashimoto, Akitoshi; Sugihara, Tsutomu; Satoh-Kubota, Ai; Suzuki-Takanami, Eri; Yano, Keiichi; Iida, Shigeru; Satoh, Mitsuo

2016-05-01

The structure of the N-linked oligosaccharides attached to antithrombin (AT) has been shown to affect its anticoagulant activity and pharmacokinetics. Human AT has biantennary complex-type oligosaccharides with the unique feature of lacking a core fucose, which affects its biological activities by changing its heparin-binding affinity. In human plasma, AT circulates as a mixture of the α-form bearing four oligosaccharides and the β-form lacking an oligosaccharide at Asn135. However, it remains unclear how the immature high-mannose-type oligosaccharides produced by mammalian cells affect biological activities of AT. Here, we succeeded in directly comparing the activities between the high-mannose and complex types. Interestingly, although there were no substantial differences in thrombin inhibitory activity, the high-mannose type showed higher heparin-binding affinity. The anticoagulant activities were increased by heparin and correlated with the heparin-binding affinity, resulting in the strongest anticoagulant activity being displayed in the β-form with the high-mannose type. In pharmacokinetic profiling, the high-mannose type showed a much shorter plasma half-life than the complex type. The β-form was found to have a prolonged plasma half-life compared with the α-form for the high-mannose type; conversely, the α-form showed a longer half-life than the β-form for the complex-type. The present study highlights that AT physiological activities are strictly controlled not only by a core fucose at the reducing end but also by the high-mannose-type structures at the nonreducing end. The β-form with the immature high-mannose type appears to function as a more potent anticoagulant than the AT typically found in human plasma, once it emerges in the blood. © The Author 2016. Published by Oxford University Press.

Quantitative structure activity relationship studies of piperazinyl phenylalanine derivatives as VLA-4/VCAM-1 inhibitors.

PubMed

Bhargava, Dinesh; Karthikeyan, C; Moorthy, N S H N; Trivedi, Piyush

2009-09-01

QSAR study was carried out for a series of piperazinyl phenylalanine derivatives exhibiting VLA-4/VCAM-1 inhibitory activity to find out the structural features responsible for the biological activity. The QSAR study was carried out on V-life Molecular Design Suite software and the derived best QSAR model by partial least square (forward) regression method showed 85.67% variation in biological activity. The statistically significant model with high correlation coefficient (r2=0.85) was selected for further study and the resulted validation parameters of the model, crossed squared correlation coefficient (q2=0.76 and pred_r2=0.42) show the model has good predictive ability. The model showed that the parameters SaaNEindex, SsClcount slogP,and 4PathCount are highly correlated with VLA-4/VCAM-1 inhibitory activity of piperazinyl phenylalanine derivatives. The result of the study suggests that the chlorine atoms in the molecule and fourth order fragmentation patterns in the molecular skeleton favour VLA-4/VCAM-1 inhibition shown by the title compounds whereas lipophilicity and nitrogen bonded to aromatic bond are not conducive for VLA-4/VCAM-1 inhibitory activity.

Ellagic Acid: A Logical Lead for Drug Development?

PubMed

Shakeri, Abolfazl; Zirak, Mohammad Reza; Sahebkar, Amirhossein

2018-01-01

Naturally occurring polyphenols are the subject of increasing attention due to their potent antioxidant activity and their marked effects on the prevention of various oxidative stress-associated diseases such as cancer. Ellagic acid (EA) is an herbal polyphenol that is structurally a condensed dimer of gallic acid. This review aims to provide a comprehensive and updated overview on the biological activities of EA and potential therapeutic applications. EA is found in fruits and nuts, either in the combined form with hexahydroxydiphenic acid or in the bound form (ellagitannins). EA exhibits many biological properties such as antioxidant, anti-diabetic, anticancer and apoptosis-inducing activities. These biological and pharmacological properties are relevant to the treatment of several human diseases. Owing to its multiple mechanisms of action, EA represents a potential therapeutic agent against human diseases particularly cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Dynamics of DNA Sequencing.

ERIC Educational Resources Information Center

Morvillo, Nancy

1997-01-01

Describes a paper-and-pencil activity that helps students understand DNA sequencing and expands student understanding of DNA structure, replication, and gel electrophoresis. Appropriate for advanced biology students who are familiar with the Sanger method. (DDR)

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials

PubMed Central

Choudhary, Alka; Naughton, Lynn M.; Montánchez, Itxaso

2017-01-01

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012–2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds. PMID:28846659

Novel Yersinia Pestis Toxin that Resembles Bacillus Anthracis Edema Factor: Study of Activity and Structural Modeling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Motin, V; Garcia, E; Barsky, D

2003-02-05

The goal of this project was to begin both experimental and computational studies of the novel plague toxin to establish its biological properties and create its 3D-model. The project was divided into two parts. (1) Experimental--This part was devoted to determine distribution of the genes encoding novel plague toxin among different isolates of Y.pestis. If the EF-like activity is important for Y.pestis pathogenicity, it is anticipated that all highly virulent strains will contain the toxin genes. Also, they proposed to initiate research to investigate the functionality of the novel Y.pestis toxin that they hypothesize is likely to significantly contribute tomore » the virulence of this dangerous microbe. this research design consisted of amplification, cloning and expression in E.coli the toxin genes followed by affinity purification of the recombinant protein that can be further used for testing of enzymatic activity. (2) Computational--The structural modeling of the putative EF of Y.pestis was based on multiple sequence alignments, secondary structure predictions, and comparison with 3D models of the EF of B. anthracis. The x-ray structure of the last has been recently published [Nature. 2002. 415(Jan):396-402]. The final model was selected after detailed analysis to determine if the structure is consistent with the biological function.« less

Evaluation of readily accessible azoles as mimics of the aromatic ring of D-phenylalanine in the turn region of gramicidin S.

PubMed

van der Knaap, Matthijs; Lageveen, Lianne T; Busscher, Henk J; Mars-Groenendijk, Roos; Noort, Daan; Otero, José M; Llamas-Saiz, Antonio L; van Raaij, Mark J; van der Marel, Gijsbert A; Overkleeft, Herman S; Overhand, Mark

2011-05-02

The influence of replacing the d-phenylalanine residue with substituted and unsubstituted azoles on the structure and biological activity of the antibiotic gramicidin S was investigated against a representative panel of Gram-positive and Gram-negative bacteria strains. Substituted triazole derivatives, obtained using a convergent synthetic strategy, are as active as gramicidin S, provided that any substituent on the triazole moiety is not too large. The unsubstituted triazole derivative was biologically less active than the parent natural product, gramicidin S. In general for the triazole series, the hemolytic activity could be correlated with the antibacterial activity, that is, the higher the antibacterial activity, the higher the toxicity towards blood cells. Interestingly, its imidazole counterpart showed high antibacterial activity, combined with significantly diminished hemolytic activity. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ZINC: A Free Tool to Discover Chemistry for Biology

PubMed Central

2012-01-01

ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org. PMID:22587354

Activation of a camptothecin prodrug by specific carboxylesterases as predicted by quantitative structure-activity relationship and molecular docking studies.

PubMed

Yoon, Kyoung Jin P; Krull, Erik J; Morton, Christopher L; Bornmann, William G; Lee, Richard E; Potter, Philip M; Danks, Mary K

2003-11-01

7-Ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (irinotecan, CPT-11) is a camptothecin prodrug that is metabolized by carboxylesterases (CE) to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38), a topoisomerase I inhibitor. CPT-11 has shown encouraging antitumor activity against a broad spectrum of tumor types in early clinical trials, but hematopoietic and gastrointestinal toxicity limit its administration. To increase the therapeutic index of CPT-11 and to develop other prodrug analogues for enzyme/prodrug gene therapy applications, our laboratories propose to develop camptothecin prodrugs that will be activated by specific CEs. Specific analogues might then be predicted to be activated, for example, predominantly by human liver CE(hCE1), by human intestinal CE (hiCE), or in gene therapy approaches using a rabbit liver CE (rCE). This study describes a molecular modeling approach to relate the structure of rCE-activated camptothecin prodrugs with their biological activation. Comparative molecular field analysis, comparative molecular similarity index analysis, and docking studies were used to predict the biological activity of a 4-benzylpiperazine derivative of CPT-11 [7-ethyl-10-[4-(1-benzyl)-1-piperazino]carbonyloxycamptothecin (BP-CPT)] in U373MG glioma cell lines transfected with plasmids encoding rCE or hiCE. BP-CPT has been reported to be activated more efficiently than CPT-11 by a rat serum esterase activity; however, three-dimensional quantitative structure-activity relationship studies predicted that rCE would activate BP-CPT less efficiently than CPT-11. This was confirmed by both growth inhibition experiments and kinetic studies. The method is being used to design camptothecin prodrugs predicted to be activated by specific CEs.

Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-binding Domain*S⃞

PubMed Central

Bottomley, Matthew J.; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-01-01

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR·HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions. PMID:18614528

Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain.

PubMed

Bottomley, Matthew J; Lo Surdo, Paola; Di Giovine, Paolo; Cirillo, Agostino; Scarpelli, Rita; Ferrigno, Federica; Jones, Philip; Neddermann, Petra; De Francesco, Raffaele; Steinkühler, Christian; Gallinari, Paola; Carfí, Andrea

2008-09-26

Histone deacetylases (HDACs) regulate chromatin status and gene expression, and their inhibition is of significant therapeutic interest. To date, no biological substrate for class IIa HDACs has been identified, and only low activity on acetylated lysines has been demonstrated. Here, we describe inhibitor-bound and inhibitor-free structures of the histone deacetylase-4 catalytic domain (HDAC4cd) and of an HDAC4cd active site mutant with enhanced enzymatic activity toward acetylated lysines. The structures presented, coupled with activity data, provide the molecular basis for the intrinsically low enzymatic activity of class IIa HDACs toward acetylated lysines and reveal active site features that may guide the design of class-specific inhibitors. In addition, these structures reveal a conformationally flexible structural zinc-binding domain conserved in all class IIa enzymes. Importantly, either the mutation of residues coordinating the structural zinc ion or the binding of a class IIa selective inhibitor prevented the association of HDAC4 with the N-CoR.HDAC3 repressor complex. Together, these data suggest a key role of the structural zinc-binding domain in the regulation of class IIa HDAC functions.

In Vitro Biologic Activities of the Antimicrobials Triclocarban, Its Analogs, and Triclosan in Bioassay Screens: Receptor-Based Bioassay Screens

PubMed Central

Ahn, Ki Chang; Zhao, Bin; Chen, Jiangang; Cherednichenko, Gennady; Sanmarti, Enio; Denison, Michael S.; Lasley, Bill; Pessah, Isaac N.; Kültz, Dietmar; Chang, Daniel P.Y.; Gee, Shirley J.; Hammock, Bruce D.

2008-01-01

Background Concerns have been raised about the biological and toxicologic effects of the antimicrobials triclocarban (TCC) and triclosan (TCS) in personal care products. Few studies have evaluated their biological activities in mammalian cells to assess their potential for adverse effects. Objectives In this study, we assessed the activity of TCC, its analogs, and TCS in in vitro nuclear-receptor–responsive and calcium signaling bioassays. Materials and methods We determined the biological activities of the compounds in in vitro, cell-based, and nuclear-receptor–responsive bioassays for receptors for aryl hydrocarbon (AhR), estrogen (ER), androgen (AR), and ryanodine (RyR1). Results Some carbanilide compounds, including TCC (1–10 μM), enhanced estradiol (E2)-dependent or testosterone-dependent activation of ER- and AR-responsive gene expression up to 2.5-fold but exhibited little or no agonistic activity alone. Some carbanilides and TCS exhibited weak agonistic and/or antagonistic activity in the AhR-responsive bioassay. TCS exhibited antagonistic activity in both ER- and AR-responsive bioassays. TCS (0.1–10 μM) significantly enhanced the binding of [3H]ryanodine to RyR1 and caused elevation of resting cytosolic [Ca2+] in primary skeletal myotubes, but carbanilides had no effect. Conclusions Carbanilides, including TCC, enhanced hormone-dependent induction of ER- and AR-dependent gene expression but had little agonist activity, suggesting a new mechanism of action of endocrine-disrupting compounds. TCS, structurally similar to noncoplanar ortho-substituted poly-chlorinated biphenyls, exhibited weak AhR activity but interacted with RyR1 and stimulated Ca2+ mobilization. These observations have potential implications for human and animal health. Further investigations are needed into the biological and toxicologic effects of TCC, its analogs, and TCS. PMID:18795164

Defining the Synthetic Biology Supply Chain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frazar, Sarah L.; Hund, Gretchen E.; Bonheyo, George T.

In this article, a team of experts in synthetic biology, data analytics, and national security describe the overall supply chain surrounding synthetic biology. The team analyzes selected interactions within that network to better understand the risks raised by synthetic biology and identifies opportunities for risk mitigation. To introduce the concept, the article will briefly describe how an understanding of supply chains has been important in promoting nuclear nonproliferation objectives. The article concludes by assessing the structure and networks identified in the supply chains to reveal potential opportunities for future biodefense research and development; options for additional information exchange; and meansmore » to interdict, detect, or deter suspicious activity.« less

The role of mechanics in biological and bio-inspired systems.

PubMed

Egan, Paul; Sinko, Robert; LeDuc, Philip R; Keten, Sinan

2015-07-06

Natural systems frequently exploit intricate multiscale and multiphasic structures to achieve functionalities beyond those of man-made systems. Although understanding the chemical make-up of these systems is essential, the passive and active mechanics within biological systems are crucial when considering the many natural systems that achieve advanced properties, such as high strength-to-weight ratios and stimuli-responsive adaptability. Discovering how and why biological systems attain these desirable mechanical functionalities often reveals principles that inform new synthetic designs based on biological systems. Such approaches have traditionally found success in medical applications, and are now informing breakthroughs in diverse frontiers of science and engineering.

Functional inclusion bodies produced in the yeast Pichia pastoris.

PubMed

Rueda, Fabián; Gasser, Brigitte; Sánchez-Chardi, Alejandro; Roldán, Mònica; Villegas, Sandra; Puxbaum, Verena; Ferrer-Miralles, Neus; Unzueta, Ugutz; Vázquez, Esther; Garcia-Fruitós, Elena; Mattanovich, Diethard; Villaverde, Antonio

2016-10-01

Bacterial inclusion bodies (IBs) are non-toxic protein aggregates commonly produced in recombinant bacteria. They are formed by a mixture of highly stable amyloid-like fibrils and releasable protein species with a significant extent of secondary structure, and are often functional. As nano structured materials, they are gaining biomedical interest because of the combination of submicron size, mechanical stability and biological activity, together with their ability to interact with mammalian cell membranes for subsequent cell penetration in absence of toxicity. Since essentially any protein species can be obtained as IBs, these entities, as well as related protein clusters (e.g., aggresomes), are being explored in biocatalysis and in biomedicine as mechanically stable sources of functional protein. One of the major bottlenecks for uses of IBs in biological interfaces is their potential contamination with endotoxins from producing bacteria. To overcome this hurdle, we have explored here the controlled production of functional IBs in the yeast Pichia pastoris (Komagataella spp.), an endotoxin-free host system for recombinant protein production, and determined the main physicochemical and biological traits of these materials. Quantitative and qualitative approaches clearly indicate the formation of IBs inside yeast, similar in morphology, size and biological activity to those produced in E. coli, that once purified, interact with mammalian cell membranes and penetrate cultured mammalian cells in absence of toxicity. Structurally and functionally similar from those produced in E. coli, the controlled production of IBs in P. pastoris demonstrates that yeasts can be used as convenient platforms for the biological fabrication of self-organizing protein materials in absence of potential endotoxin contamination and with additional advantages regarding, among others, post-translational modifications often required for protein functionality.

Identification of Functionally Related Enzymes by Learning-to-Rank Methods.

PubMed

Stock, Michiel; Fober, Thomas; Hüllermeier, Eyke; Glinca, Serghei; Klebe, Gerhard; Pahikkala, Tapio; Airola, Antti; De Baets, Bernard; Waegeman, Willem

2014-01-01

Enzyme sequences and structures are routinely used in the biological sciences as queries to search for functionally related enzymes in online databases. To this end, one usually departs from some notion of similarity, comparing two enzymes by looking for correspondences in their sequences, structures or surfaces. For a given query, the search operation results in a ranking of the enzymes in the database, from very similar to dissimilar enzymes, while information about the biological function of annotated database enzymes is ignored. In this work, we show that rankings of that kind can be substantially improved by applying kernel-based learning algorithms. This approach enables the detection of statistical dependencies between similarities of the active cleft and the biological function of annotated enzymes. This is in contrast to search-based approaches, which do not take annotated training data into account. Similarity measures based on the active cleft are known to outperform sequence-based or structure-based measures under certain conditions. We consider the Enzyme Commission (EC) classification hierarchy for obtaining annotated enzymes during the training phase. The results of a set of sizeable experiments indicate a consistent and significant improvement for a set of similarity measures that exploit information about small cavities in the surface of enzymes.

Anti-ulcer agents: chemical aspect of solving the problem

NASA Astrophysics Data System (ADS)

Rogoza, L. N.; Salakhutdinov, N. F.

2015-01-01

The data on chemical structures and specific activities of compounds functioning as histamine H2-receptor antagonists, H+/K+-ATPase inhibitors at the exchange sites of hydrogen ions (proton pump inhibitors) and potassium ions (K+-competitive acid blockers) published from 1990 to 2013 are surveyed. The antisecretory agents with studied cytoprotective activity or with additional therapeutic properties compensating for disorders of internal defence mechanisms are presented. A separate section is devoted to the drugs that prevent or mitigate the NSAID-induced intestinal damage. All of the considered structures are classified according to the type of biological mechanism of action. Some aspects of the structure-activity relationships for such compounds are considered. The bibliography includes 83 references.

Dye surface coating enables visible light activation of TiO2 nanoparticles leading to degradation of neighboring biological structures.

PubMed

Blatnik, Jay; Luebke, Lanette; Simonet, Stephanie; Nelson, Megan; Price, Race; Leek, Rachael; Zeng, Leyong; Wu, Aiguo; Brown, Eric

2012-02-01

Biologically and chemically modified nanoparticles are gaining much attention as a new tool in cancer detection and treatment. Herein, we demonstrate that an alizarin red S (ARS) dye coating on TiO2 nanoparticles enables visible light activation of the nanoparticles leading to degradation of neighboring biological structures through localized production of reactive oxygen species. Successful coating of nanoparticles with dye is demonstrated through sedimentation, spectrophotometry, and gel electrophoresis techniques. Using gel electrophoresis, we demonstrate that visible light activation of dye-TiO2 nanoparticles leads to degradation of plasmid DNA in vitro. Alterations in integrity and distribution of nuclear membrane associated proteins were detected via fluorescence confocal microscopy in HeLa cells exposed to perinuclear localized ARS-TiO2 nanoparticles that were photoactivated with visible light. This study expands upon previous studies that indicated dye coatings on TiO2 nanoparticles can serve to enhance imaging, by clearly showing that dye coatings on TiO2 nanoparticles can also enhance the photoreactivity of TiO2 nanoparticles by allowing visible light activation. The findings of our study suggest a therapeutic application of dye-coated TiO2 nanoparticles in cancer research; however, at the same time they may reveal limitations on the use of dye assisted visualization of TiO2 nanoparticles in live-cell imaging.

Synthesis, crystal structure and larvicidal activity of novel diamide derivatives against Culex pipiens.

PubMed

Wu, Rui; Zhu, Cong; Du, Xiu-Jiang; Xiong, Li-Xia; Yu, Shu-Jing; Liu, Xing-Hai; Li, Zheng-Ming; Zhao, Wei-Guang

2012-09-11

Culex is an important mosquito as vectors for the transmission of serious diseases, such as filariasis, West Nile virus, dengue, yellow fever, chikungunya and other encephalitides. Nearly one billion people in the developing countries are at risk. In order to discover new bioactive molecules and pesticides acting on mosquito, we designed active amide structure and synthesized a series of novel diamide derivatives. A series of novel diamide derivatives were designed and synthesized. Their structures were characterized by 1 H NMR, FTIR and HRMS. The single crystal structure of compound 6n was determined to further elucidate the structure. Biological activities of these compounds were tested. Most of them exhibited higher mosquito larvicidal activity. Especially compound 6r displayed relatively good activity to reach 70% at 2 μg/mL. A practical synthetic route to amide derivatives by the reaction of amide with another acid is presented. This study suggests that the diamide derivatives exhibited good effective against mosquito.

Nano-swimmers in biological membranes and propulsion hydrodynamics in two dimensions.

PubMed

Huang, Mu-Jie; Chen, Hsuan-Yi; Mikhailov, Alexander S

2012-11-01

Active protein inclusions in biological membranes can represent nano-swimmers and propel themselves in lipid bilayers. A simple model of an active inclusion with three particles (domains) connected by variable elastic links is considered. First, the membrane is modeled as a two-dimensional viscous fluid and propulsion behavior in two dimensions is examined. After that, an example of a microscopic dynamical simulation is presented, where the lipid bilayer structure of the membrane is resolved and the solvent effects are included by multiparticle collision dynamics. Statistical analysis of data reveals ballistic motion of the swimmer, in contrast to the classical diffusion behavior found in the absence of active transitions between the states.

Structural and Biological Behaviour of Co(II), Cu(II) and Ni(II) Metal Complexes of Some Amino Acid Derived Schiff-Bases

PubMed Central

Chohan, Zahid H.; Praveen, M.; Ghaffar, A.

1997-01-01

Biologically active tridentate amino acid (Alanine, Glycine & Tyrosine) derived Schiff-bases and their Co(II), Cu(II) & Ni(II) complexes have been synthesised and characterised on the basis of their conductance and magnetic measurements, elemental analysis and 13C-NMR, 1H-NMR, IR and electronic spectral data. These Schiff-bases and their complexes have been evaluated for their antibacterial activity against bacterial species such as Staphylococcus aureus, Escherichia coli, Klebsiella pneumonae, Proteus vulgarus and Pseudomonas aeruginosa and this activity data show the metal complexes to be more antibacterial than the Schiff-bases against one or more bacterial species. PMID:18475798

The case for biophysics super-groups in physics departments.

PubMed

Hoogenboom, Bart W; Leake, Mark

2018-06-04

Increasing numbers of physicists engage in research activities that address biological questions from physics perspectives or strive to develop physics insights from active biological processes. The on-going development and success of such activities morph our ways of thinking about what it is to 'do biophysics' and add to our understanding of the physics of life. Many scientists in this research and teaching landscape are homed in physics departments. A challenge for a hosting department is how to group, name and structure such biophysicists to best add value to their emerging research and teaching but also to the portfolio of the whole department. Here we discuss these issues and speculate on strategies. Creative Commons Attribution license.

Mössbauer effect study of iron(III) inidazolidine nitroxyl-free radical ligand complex

NASA Astrophysics Data System (ADS)

Mulaba, A.; Kiremire, E.; Pollak, H.; Boeyens, J.

1999-09-01

A new complex, [Fe(acac)L2], bearing inidazolidine nitroxyl-free radical ligand (L-) was recently synthesised for biological studies. It proved to be biologically active against African sleeping sickness, plasmodium falciparum (malaria), leishmaniasis and chaga disease causative agents. Three ESR well resolved peaks indicated the presence of a free (unpaired) and chemically active electron in the complex. The structural complex ferric iron was found at the centre of two electric gradient whose the biggest is suggested to be initiated by the unpaired charge. No distinction between different cis isomers could be made.

Novel approaches to determine contractile function of the isolated adult zebrafish ventricular cardiac myocyte.

PubMed

Dvornikov, Alexey V; Dewan, Sukriti; Alekhina, Olga V; Pickett, F Bryan; de Tombe, Pieter P

2014-05-01

The zebrafish (Danio rerio) has been used extensively in cardiovascular biology, but mainly in the study of heart development. The relative ease of its genetic manipulation may indicate the suitability of this species as a cost-effective model system for the study of cardiac contractile biology. However, whether the zebrafish heart is an appropriate model system for investigations pertaining to mammalian cardiac contractile structure-function relationships remains to be resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic digestion, attached to carbon rods, and twitch force and intracellular Ca(2+) were measured. We observed the modulation of twitch force, but not of intracellular Ca(2+), by both extracellular [Ca(2+)] and sarcomere length. In permeabilized cells/myofibrils, we found robust myofilament length-dependent activation. Moreover, modulation of myofilament activation-relaxation and force redevelopment kinetics by varied Ca(2+) activation levels resembled that found previously in mammalian myofilaments. We conclude that the zebrafish is a valid model system for the study of cardiac contractile structure-function relationships.

Optimization of polysaccharides extraction from watermelon rinds: Structure, functional and biological activities.

PubMed

Romdhane, Molka Ben; Haddar, Anissa; Ghazala, Imen; Jeddou, Khawla Ben; Helbert, Claire Boisset; Ellouz-Chaabouni, Semia

2017-02-01

In the present work, optimization of hot water extraction, structural characteristics, functional properties, and biological activities of polysaccharides extracted from watermelon rinds (WMRP) were investigated. The physicochemical characteristics and the monosaccharide composition of these polysaccharides were then determined using chemical composition analysis, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and gas chromatography-flame ionization detection (GC-FID). SEM images showed that extracted polysaccharides had a rough surface with many cavities. GC-FID results proved that galactose was the dominant sugar in the extracted polysaccharides, followed by arabinose, glucose, galacturonic acid, rhamnose, mannose, xylose and traces of glucuronic acid. The findings revealed that WMRP displayed excellent antihypertensive and antioxidant activities. Those polysaccharides had also a protection effect against hydroxyl radical-induced DNA damage. Functional properties of extracted polysaccharides were also evaluated. WMRP showed good interfacial dose-dependent proprieties. Overall, the results suggested that WMRP presents a promising natural source of antioxidants and antihypertensive agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Design and Synthesis of Highly Potent HIV-1 Protease Inhibitors Containing Tricyclic Fused Ring Systems as Novel P2 Ligands: Structure-Activity Studies, Biological and X-ray Structural Analysis.

PubMed

Ghosh, Arun K; R Nyalapatla, Prasanth; Kovela, Satish; Rao, Kalapala Venkateswara; Brindisi, Margherita; Osswald, Heather L; Amano, Masayuki; Aoki, Manabu; Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T; Mitsuya, Hiroaki

2018-05-24

The design, synthesis, and biological evaluation of a new class of HIV-1 protease inhibitors containing stereochemically defined fused tricyclic polyethers as the P2 ligands and a variety of sulfonamide derivatives as the P2' ligands are described. A number of ring sizes and various substituent effects were investigated to enhance the ligand-backbone interactions in the protease active site. Inhibitors 5c and 5d containing this unprecedented fused 6-5-5 ring system as the P2 ligand, an aminobenzothiazole as the P2' ligand, and a difluorophenylmethyl as the P1 ligand exhibited exceptional enzyme inhibitory potency and maintained excellent antiviral activity against a panel of highly multidrug-resistant HIV-1 variants. The umbrella-like P2 ligand for these inhibitors has been synthesized efficiently in an optically active form using a Pauson-Khand cyclization reaction as the key step. The racemic alcohols were resolved efficiently using a lipase catalyzed enzymatic resolution. Two high resolution X-ray structures of inhibitor-bound HIV-1 protease revealed extensive interactions with the backbone atoms of HIV-1 protease and provided molecular insight into the binding properties of these new inhibitors.

Stereoselective synthesis, X-ray analysis, computational studies and biological evaluation of new thiazole derivatives as potential anticancer agents.

PubMed

Mabkhot, Yahia N; Alharbi, Mohammed M; Al-Showiman, Salim S; Ghabbour, Hazem A; Kheder, Nabila A; Soliman, Saied M; Frey, Wolfgang

2018-05-11

The synthesis of new thiazole derivatives is very important because of their diverse biological activities. Also , many drugs containing thiazole ring in their skeletons are available in the market such as Abafungin, Acotiamide, Alagebrium, Amiphenazole, Brecanavir, Carumonam, Cefepime, and Cefmatilen. Ethyl cyanoacetate reacted with phenylisothiocyanate, chloroacetone, in two different basic mediums to afford the thiazole derivative 6, which reacted with dimethylformamide- dimethyl acetal in the presence of DMF to afford the unexpected thiazole derivative 11. The structures of the thiazoles 6 and 11 were optimized using B3LYP/6-31G(d,p) method. The experimentally and theoretically geometric parameters agreed very well. Also, the natural charges at the different atomic sites were predicted. HOMO and LUMO demands were discussed. The anticancer activity of the prepared compounds was evaluated and showed moderate activity. Synthesis of novel thiazole derivatives was done. The structure was established using X-ray and spectral analysis. Optimized molecular structures at the B3LYP/6-31G(d,p) level were investigated. Thiazole derivative 11 has more electropositive S-atom than thiazole 6. The HOMO-LUMO energy gap is lower in the former compared to the latter. The synthesized compounds showed moderate anticancer activity.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beauchamp, R.O. Jr.

A preliminary examination of chemical-substructure analysis (CSA) demonstrates the effective use of the Chemical Abstracts compound connectivity file in conjunction with the bibliographic file for relating chemical structures to biological activity. The importance of considering the role of metabolic intermediates under a variety of conditions is illustrated, suggesting structures that should be examined that may exhibit potential activity. This CSA technique, which utilizes existing large files accessible with online personal computers, is recommended for use as another tool in examining chemicals in drugs. 2 refs., 4 figs.

Mono-carbonyl curcumin analogues as 11β-hydroxysteroid dehydrogenase 1 inhibitors.

PubMed

Lin, Han; Hu, Guo-Xin; Guo, Jingjing; Ge, Yufei; Liang, Guang; Lian, Qing-Quan; Chu, Yanhui; Yuan, Xiaohuan; Huang, Ping; Ge, Ren-Shan

2013-08-01

A series of structurally novel mono-carbonyl curcumin analogues have been synthesized and biologically evaluated to test their inhibitory potencies and the structure-activity relationship (SAR) on human and rat 11β-hydroxysteroid dehydrogenase isoform (11β-HSD1) activities. 11β-HSD1 selective inhibitors have been discovered and compound A10 is discovered as a very potent with an IC50 value of 97 nM without inhibiting 11β-HSD2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Polyphenols, their metabolites and derivatives as drug leads.

PubMed

Almeida, Filipa A; Dos Santos, Cláudia Nunes; Ventura, Maria Rita

2018-05-15

In this non-comprehensive review, the potential of natural polyphenols as lead compounds for the design and synthesis of new molecules with potential application in several diseases was highlighted. Organic synthesis has been essential for the development of new analogues of naturally found polyphenols, providing a wide range of structural modifications for structure-activity relationship studies and improving or modulating the biological activity of the promising compounds. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Novel active principles from spider venom.

PubMed

Vassilevski, Alexander A; Grishin, Eugene V

2011-12-01

Spiders are one of the most intriguing groups of venomous animals. Substances found in their venom vary from simple inorganic compounds to large multi-domain proteins. In this article, we review some of the latest work presenting active principles that add to the known spider toxin universe. Two aspects of novelty are addressed in particular, structural (novel types of molecules in terms of structure) and functional (novel types of biological targets hit by substances from spider venom and novel mechanisms of action).

The Redox Proteome*

PubMed Central

Go, Young-Mi; Jones, Dean P.

2013-01-01

The redox proteome consists of reversible and irreversible covalent modifications that link redox metabolism to biologic structure and function. These modifications, especially of Cys, function at the molecular level in protein folding and maturation, catalytic activity, signaling, and macromolecular interactions and at the macroscopic level in control of secretion and cell shape. Interaction of the redox proteome with redox-active chemicals is central to macromolecular structure, regulation, and signaling during the life cycle and has a central role in the tolerance and adaptability to diet and environmental challenges. PMID:23861437

Using Plants to Explore the Nature & Structural Complexity of Life

ERIC Educational Resources Information Center

Howard, Ava R.

2014-01-01

Use of real specimens brings the study of biology to life. This activity brings easily acquired plant specimens into the classroom to tackle common alternative conceptions regarding life, size, complexity, the nature of science, and plants as multicellular organisms. The activity occurs after a discussion of the characteristics of life and engages…

Phellodonic acid, a new biologically active hirsutane derivative from Phellodon melaleucus (Thelephoraceae, Basidiomycetes).

PubMed

Stadler, M; Anke, T; Dasenbrock, J; Steglich, W

1993-01-01

A new hirsutane derivative, phellodonic acid (1), has been isolated from fermentations of Phellodon melaleucus strain 87113. Its structure was elucidated by spectroscopic methods. The compound exhibits antibiotic activities towards bacteria and fungi. 1 is the first bioactive metabolite from cultures of a species belonging to the family Thelephoraceae.

Molecular Mechanics and Dynamics Characterization of an "in silico" Mutated Protein: A Stand-Alone Lab Module or Support Activity for "in vivo" and "in vitro" Analyses of Targeted Proteins

ERIC Educational Resources Information Center

Chiang, Harry; Robinson, Lucy C.; Brame, Cynthia J.; Messina, Troy C.

2013-01-01

Over the past 20 years, the biological sciences have increasingly incorporated chemistry, physics, computer science, and mathematics to aid in the development and use of mathematical models. Such combined approaches have been used to address problems from protein structure-function relationships to the workings of complex biological systems.…

Molecular mechanisms of immunosuppression.

PubMed

Baumann, G; Zenke, G; Wenger, R; Hiestand, P; Quesniaux, V; Andersen, E; Schreier, M H

1992-04-01

The immunosuppressive drug cyclosporin A (CsA, Sandimmun, SIM) is currently being evaluated in a variety of autoimmune disorders with some remarkable successes. Despite the wide empiric application of CsA, the precise mechanism of action of this drug remains elusive. To identify the molecular mode of action of CsA in the process of T cell activation, we have compared the biological profile of cyclophilin-binding cyclosporin analogues (CBCA), which lack immunosuppressive properties, with CsA. We have found that CsA binding to its intracellular receptor (cyclophilin) is required but not sufficient for immunosuppression. Moreover, inhibition of the peptidyl-prolyl cis-trans isomerase activity of cyclophilin does not seem to be relevant for the inhibitory effects of CsA. In analogy to the immunosuppressants FK506 and rapamycin, a specific structure at the 'effector' domain of the CsA molecule different from the immunophilin 'binding' domain determines the biological activity. Overall, a significant understanding of the structure-activity relationship of CsA has emerged. This will have a major impact on the identification of the precise mechanism of action of CsA and its side effects in the process of immunosuppression.

Antifungal potential of marine natural products.

PubMed

El-Hossary, Ebaa M; Cheng, Cheng; Hamed, Mostafa M; El-Sayed Hamed, Ashraf Nageeb; Ohlsen, Knut; Hentschel, Ute; Abdelmohsen, Usama Ramadan

2017-01-27

Fungal diseases represent an increasing threat to human health worldwide which in some cases might be associated with substantial morbidity and mortality. However, only few antifungal drugs are currently available for the treatment of life-threatening fungal infections. Furthermore, plant diseases caused by fungal pathogens represent a worldwide economic problem for the agriculture industry. The marine environment continues to provide structurally diverse and biologically active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. Among these secondary metabolites, several compounds with noteworthy antifungal activities have been isolated from marine microorganisms, invertebrates, and algae. During the last fifteen years, around 65% of marine natural products possessing antifungal activities have been isolated from sponges and bacteria. This review gives an overview of natural products from diverse marine organisms that have shown in vitro and/or in vivo potential as antifungal agents, with their mechanism of action whenever applicable. The natural products literature is covered from January 2000 until June 2015, and we are reporting the chemical structures together with their biological activities, as well as the isolation source. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Occurrence, Functions and Biological Significance of Arginine-Rich Proteins.

PubMed

Chandana, Thimmegowda; Venkatesh, Yeldur P

2016-01-01

Arginine, the most basic among the 20 amino acids, occurs less frequently than lysine in proteins despite being coded by six codons. Only a few important proteins of biological significance have been found to be abundant in arginine. It has been established that these arginine-rich proteins have been assigned important roles in the biological systems. Arginine-rich cationic proteins are known to stabilize macromolecular structures by establishing appropriate interactions (salt bridges, hydrogen bonds and cation-π interactions). These proteins are also known to be the key members of many regulatory pathways such as gene expression, chromatin stability, expurgation of introns from naïve mRNA, mRNA splicing, membrane-penetrating activity and pathogenesis-related defense, to name a few. Further, arginine occurs in various combinations with other amino acids (serine, lysine, proline, tryptophan, valine, glycine and glutamic acid) which diversify the potential functions of arginine-rich proteins. Arginine-rich proteins known till date from dietary sources have been described in terms of their structure and functional properties. A variety of activities such as bactericidal, membrane-penetrating, antimicrobial, anti-hypertensive, pro-angiogenic and others have been reported for arginine-rich proteins. This review attempts to collate the occurrence, functions and the biological significance of this unique class of proteins rich in arginine.

Steroidogenesis in the skin: implications for local immune functions

PubMed Central

Slominski, Andrzej; Zbytek, Bazej; Nikolakis, Georgios; Manna, Pulak R.; Skobowiat, Cezary; Zmijewski, Michal; Li, Wei; Janjetovic, Zorica; Postlethwaite, Arnold; Zouboulis, Christos C.; Tuckey, Robert C.

2013-01-01

The skin has developed a hierarchy of systems that encompasses the skin immune and local steroidogenic activities in order to protect the body against the external environment and biological factors and to maintain local homeostasis. Most recently it has been established that skin cells contain the entire biochemical apparatus necessary for production of glucocorticoids, androgens and estrogens either from precursors of systemic origin or, alternatively, through the conversion of cholesterol to pregnenolone and its subsequent transformation to biologically active steroids. Examples of these products are corticosterone, cortisol, testosterone, dihydrotesterone and estradiol. Their local production can be regulated by locally produced corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) or cytokines. Furthermore the production of glucocorticoids is affected by ultraviolet B radiation. The level of production and nature of the final steroid products are dependent on the cell type or cutaneous compartment, e.g., epidermis, dermis, adnexal structures or adipose tissue. Locally produced glucocorticoids, androgens and estrogens affect functions of the epidermis and adnexal structures as well as local immune activity. Malfunction of these steroidogenic activities can lead to inflammatory disorders or autoimmune diseases. The cutaneous steroidogenic system can also have systemic effects, which are emphasized by significant skin contribution to circulating androgens and/or estrogens. Furthermore, local activity of CYP11A1 can produce novel 7 -steroids and secosteroids that are biologically active. Therefore, modulation of local steroidogenic activity may serve as a new therapeutic approach for treatment of inflammatory disorders, autoimmune processes or other skin disorders. In conclusion, the skin can be defined as an independent steroidogenic organ, whose activity can affect its functions and the development of local or systemic inflammatory or autoimmune diseases. PMID:23435015

Characteristics of Hydrothermal Mineralization in Ultraslow Spreading Ridges

NASA Astrophysics Data System (ADS)

Zhou, H.; Yang, Q.; Ji, F.; Dick, H. J.

2014-12-01

Hydrothermal activity is a major component of the processes that shape the composition and structure of the ocean crust, providing a major pathway for the exchange of heat and elements between the Earth's crust and oceans, and a locus for intense biological activity on the seafloor and underlying crust. In other hand, the structure and composition of hydrothermal systems are the result of complex interactions between heat sources, fluids, wall rocks, tectonic controls and even biological processes. Ultraslow spreading ridges, including the Southwest Indian Ridge, the Gakkel Ridge, are most remarkable end member in plate-boundary structures (Dick et al., 2003), featured with extensive tectonic amagmatic spreading and frequent exposure of peridotite and gabbro. With intensive surveys in last decades, it is suggested that ultraslow ridges are several times more effective than faster-spreading ridges in sustaining hydrothermal activities. This increased efficiency could attributed to deep mining of heat and even exothermic serpentinisation (Baker et al., 2004). Distinct from in faster spreading ridges, one characteristics of hydrothermal mineralization on seafloor in ultraslow spreading ridges, including the active Dragon Flag hydrothermal field at 49.6 degree of the Southwest Indian Ridge, is abundant and pervasive distribution of lower temperature precipitated minerals ( such as Fe-silica or silica, Mn (Fe) oxides, sepiolite, pyrite, marcasite etc. ) in hydrothermal fields. Structures formed by lower temperature activities in active and dead hydrothermal fields are also obviously. High temperature precipitated minerals such as chalcopyrite etc. are rare or very limited in hydrothermal chimneys. Distribution of diverse low temperature hydrothermal activities is consistence with the deep heating mechanisms and hydrothermal circulations in the complex background of ultraslow spreading tectonics. Meanwhile, deeper and larger mineralization at certain locations along the ultraslow spreading ridges is also presumable.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kufareva, Irina; Gustavsson, Martin; Zheng, Yi

Chemokines and their cell surface G protein–coupled receptors are critical for cell migration, not only in many fundamental biological processes but also in inflammatory diseases and cancer. Recent X-ray structures of two chemokines complexed with full-length receptors provided unprecedented insight into the atomic details of chemokine recognition and receptor activation, and computational modeling informed by new experiments leverages these insights to gain understanding of many more receptor:chemokine pairs. In parallel, chemokine receptor structures with small molecules reveal the complicated and diverse structural foundations of small molecule antagonism and allostery, highlight the inherent physicochemical challenges of receptor:chemokine interfaces, and suggest novelmore » epitopes that can be exploited to overcome these challenges. The structures and models promote unique understanding of chemokine receptor biology, including the interpretation of two decades of experimental studies, and will undoubtedly assist future drug discovery endeavors.« less

Feasibility Analysis of Incorporating In-Vitro Toxicokinetic Data as a Surrogate for In-Vivo Data for Read-across Predictions (ASCCT meeting)

EPA Science Inventory

The underlying principle of read-across is that biological activity is a function of physical and structural properties of chemicals. Analogs are typically identified on the basis of structural similarity and subsequently evaluated for their use in read-across on the basis of the...

Exploration of the Energy Landscape of Acetylcholinesterase by Molecular Dynamics Simulation.

NASA Astrophysics Data System (ADS)

McCammon, J. Andrew

2002-03-01

Proteins have rough energy landscapes. Often more states than just the ground state are occupied and have biological functions. It is essential to study these conformational substates and the dynamical transitions among them. Acetylcholinesterase (AChE) is an important enzyme that has biological functions including the termination of synaptic transmission signals. X-ray structures show that it has an active site that is accessible only via a long and narrow channel from its surface. Therefore the fact that acetylcholine and larger ligands can reach the active site is believed to reflect the protein's structural fluctuation. We carried out long molecular dynamics simulations to investigate the dynamics of AChE and its relation to biological function, and compared our results with experiments. The results reveal several "doors" that open intermittantly between the active site and the surface. Instead of having simple exponential decay correlation functions, the time series of these channels reveal complex, fractal gating between conformations. We also compared the AChE dynamics data with those from an AchE-fasciculin complex. (Fasciculin is a small protein that is a natural inhibitor of AChE.) The results show remarkable effects of the protein-protein interaction, including allosteric and dynamical inhibition by fasciculin besides direct steric blocking. More information and images can be found at http://mccammon.ucsd.edu

[Microbial community structure in bio-ceramics and biological activated carbon analyzed by PCR-SSCP technique].

PubMed

Liu, Xiao-Lin; Liu, Wen-Jun

2007-04-01

Analyses of microbial community structure in bio-ceramics (BC) and biological activated carbon (BAC), which widely used in drinking water treatment were performed by polymerase-chain-reaction-single-strand-conformation-polymorphism (PCR-SSCP) targeted eubacterial 16S ribosomal RNA gene. Microorganisms on bio-ceramics and biological activated carbon were detached by ultrasonic, culturing on R2A and LB agar, respectively, followed by genome DNA extracting. Results show that larger than 10 kb genome DNA could be extracted from all the samples except the BAC samples processed by ultrasonic. However, quantities of the extracted DNA were different. 408 bp gene fragments were observed after PCR using the extracted genome DNA as templates. These gene fragments were digested with lambda exonuclease followed by SSCP electrophoresis. Same SSCP profiles were observed between ultrasonic eluting, R2A and LB agar culturing. The identity of the segment from bio-ceramics with uncultured Pseudomonas sp. Clone FTL201 16S rDNA (GenBank, AF509293.1) fragment was 92%, and identities of the two segments from BAC with Bacillus sp. JH19 16S rDNA (GenBank , DQ232748.1) fragment and Bacterium VA-S-11 16S rDNA (GenBank, AY395279.1) fragment were 100% and 99%, respectively.

A Novel Characterization of Amalgamated Networks in Natural Systems

PubMed Central

Barranca, Victor J.; Zhou, Douglas; Cai, David

2015-01-01

Densely-connected networks are prominent among natural systems, exhibiting structural characteristics often optimized for biological function. To reveal such features in highly-connected networks, we introduce a new network characterization determined by a decomposition of network-connectivity into low-rank and sparse components. Based on these components, we discover a new class of networks we define as amalgamated networks, which exhibit large functional groups and dense connectivity. Analyzing recent experimental findings on cerebral cortex, food-web, and gene regulatory networks, we establish the unique importance of amalgamated networks in fostering biologically advantageous properties, including rapid communication among nodes, structural stability under attacks, and separation of network activity into distinct functional modules. We further observe that our network characterization is scalable with network size and connectivity, thereby identifying robust features significant to diverse physical systems, which are typically undetectable by conventional characterizations of connectivity. We expect that studying the amalgamation properties of biological networks may offer new insights into understanding their structure-function relationships. PMID:26035066

Fluorescein isothiocyanate-labeled human plasma fibronectin in extracellular matrix remodeling.

PubMed

Hoffmann, Celine; Leroy-Dudal, Johanne; Patel, Salima; Gallet, Olivier; Pauthe, Emmanuel

2008-01-01

Fluorescein isothiocyanate (FITC) is a well-known probe for labeling biologically relevant proteins. However, the impact of the labeling procedure on protein structure and biological activities remains unclear. In this work, FITC-labeled human plasma fibronectin (Fn) was developed to gain insight into the dynamic relationship between cells and Fn. The similarities and differences concerning the structure and function between Fn-FITC and standard Fn were evaluated using biochemical as well as cellular approaches. By varying the FITC/Fn ratio, we demonstrated that overlabeling (>10 FITC molecules/Fn molecule) induces probe fluorescence quenching, protein aggregation, and cell growth modifications. A correct balance between reliable fluorescence for detection and no significant modifications to structure and biological function compared with standard Fn was obtained with a final ratio of 3 FITC molecules per Fn molecule (Fn-FITC3). Fn-FITC3, similar to standard Fn, is correctly recruited into the cell matrix network. Also, Fn-FITC3 is proposed to be a powerful molecular tool to investigate Fn organization and cellular behavior concomitantly.

QSAR Methods.

PubMed

Gini, Giuseppina

2016-01-01

In this chapter, we introduce the basis of computational chemistry and discuss how computational methods have been extended to some biological properties and toxicology, in particular. Since about 20 years, chemical experimentation is more and more replaced by modeling and virtual experimentation, using a large core of mathematics, chemistry, physics, and algorithms. Then we see how animal experiments, aimed at providing a standardized result about a biological property, can be mimicked by new in silico methods. Our emphasis here is on toxicology and on predicting properties through chemical structures. Two main streams of such models are available: models that consider the whole molecular structure to predict a value, namely QSAR (Quantitative Structure Activity Relationships), and models that find relevant substructures to predict a class, namely SAR. The term in silico discovery is applied to chemical design, to computational toxicology, and to drug discovery. We discuss how the experimental practice in biological science is moving more and more toward modeling and simulation. Such virtual experiments confirm hypotheses, provide data for regulation, and help in designing new chemicals.

Inferring network structure from cascades.

PubMed

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

Rational design, synthesis, biologic evaluation, and structure-activity relationship studies of novel 1-indanone alpha(1)-adrenoceptor antagonists.

PubMed

Li, Minyong; Xia, Lin

2007-11-01

In the present report, a novel series of 1-indanone alpha(1)-adrenoceptor antagonists were designed and synthesized based on 3D-pharmacophore model. Their in vitro alpha(1)-adrenoceptor antagonistic assay showed that three compounds (2a, 2m, and 2o) had similar or improved alpha(1)-adrenoceptor antagonistic activities relative to the positive control prazosin. Based on these results, a three-dimensional quantitative structure-activity relationship study was performed using a Self-Organizing Molecular Field Analysis method to provide insight for the future development of alpha(1)-adrenoceptor antagonists.

Inferring network structure from cascades

NASA Astrophysics Data System (ADS)

Ghonge, Sushrut; Vural, Dervis Can

2017-07-01

Many physical, biological, and social phenomena can be described by cascades taking place on a network. Often, the activity can be empirically observed, but not the underlying network of interactions. In this paper we offer three topological methods to infer the structure of any directed network given a set of cascade arrival times. Our formulas hold for a very general class of models where the activation probability of a node is a generic function of its degree and the number of its active neighbors. We report high success rates for synthetic and real networks, for several different cascade models.

Chemistry and biology of ω-3 PUFA peroxidation-derived compounds.

PubMed

Wang, Weicang; Yang, Haixia; Johnson, David; Gensler, Catherine; Decker, Eric; Zhang, Guodong

2017-09-01

The ω-3 polyunsaturated fatty acids (PUFAs) are among the most popular dietary supplements in the US, but they are chemically unstable and highly prone to lipid peroxidation. Many studies performed in different countries demonstrate that the majority of ω-3 PUFA products on the market are oxidized, suggesting that the resulting ω-3 PUFA peroxidation-derived compounds could be widely consumed by the general public. Therefore, it is of practical importance to understand the effects of these oxidized lipid compounds on human health. In this review, we summarize and discuss the chemical structures and biological activities of ω-3 PUFA peroxidation-derived compounds, and emphasize the importance to better understand the role of lipid peroxidation in biological activities of ω-3 PUFAs. Copyright © 2016 Elsevier Inc. All rights reserved.

The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry–Biology Interface

PubMed Central

2017-01-01

A Perspective of work in our laboratory on the examination of biologically active compounds, especially natural products, is presented. In the context of individual programs and along with a summary of our work, selected cases are presented that illustrate the impact single atom changes can have on the biological properties of the compounds. The examples were chosen to highlight single heavy atom changes that improve activity, rather than those that involve informative alterations that reduce or abolish activity. The examples were also chosen to illustrate that the impact of such single-atom changes can originate from steric, electronic, conformational, or H-bonding effects, from changes in functional reactivity, from fundamental intermolecular interactions with a biological target, from introduction of a new or altered functionalization site, or from features as simple as improvements in stability or physical properties. Nearly all the examples highlighted represent not only unusual instances of productive deep-seated natural product modifications and were introduced through total synthesis but are also remarkable in that they are derived from only a single heavy atom change in the structure. PMID:28945374

Novel thrombopoietin mimetic peptides bind c-Mpl receptor: Synthesis, biological evaluation and molecular modeling.

PubMed

Liu, Yaquan; Tian, Fang; Zhi, Dejuan; Wang, Haiqing; Zhao, Chunyan; Li, Hongyu

2017-02-01

Thrombopoietin (TPO) acts in promoting the proliferation of hematopoietic stem cells and by initiating specific maturation events in megakaryocytes. Now, TPO-mimetic peptides with amino acid sequences unrelated to TPO are of considerable pharmaceutical interest. In the present paper, four new TPO mimetic peptides that bind and activate c-Mpl receptor have been identified, synthesized and tested by Dual-Luciferase reporter gene assay for biological activities. The molecular modeling research was also approached to understand key molecular mechanisms and structural features responsible for peptide binding with c-Mpl receptor. The results presented that three of four mimetic peptides showed significant activities. In addition, the molecular modeling approaches proved hydrophobic interactions were the driven positive forces for binding behavior between peptides and c-Mpl receptor. TPO peptide residues in P7, P13 and P7' positions were identified by the analysis of hydrogen bonds and energy decompositions as the key ones for benefiting better biological activities. Our data suggested the synthesized peptides have considerable potential for the future development of stable and highly active TPO mimetic peptides. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development and implementation of (Q)SAR modeling within the CHARMMing web-user interface.

PubMed

Weidlich, Iwona E; Pevzner, Yuri; Miller, Benjamin T; Filippov, Igor V; Woodcock, H Lee; Brooks, Bernard R

2015-01-05

Recent availability of large publicly accessible databases of chemical compounds and their biological activities (PubChem, ChEMBL) has inspired us to develop a web-based tool for structure activity relationship and quantitative structure activity relationship modeling to add to the services provided by CHARMMing (www.charmming.org). This new module implements some of the most recent advances in modern machine learning algorithms-Random Forest, Support Vector Machine, Stochastic Gradient Descent, Gradient Tree Boosting, so forth. A user can import training data from Pubchem Bioassay data collections directly from our interface or upload his or her own SD files which contain structures and activity information to create new models (either categorical or numerical). A user can then track the model generation process and run models on new data to predict activity. © 2014 Wiley Periodicals, Inc.

Quantitative structure-activity relationships (QSAR) of some 2,2-diphenyl propionate (DPP) derivatives of muscarinic antagonists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gordon, R.K.; Breuer, E.; Padilla, F.N.

1987-05-01

QSAR between biological activities and molecular-chemical properties were investigated to aid in designing more effective and potent antimuscarinic pharmacophores. A molecular modeling program was used to calculate geometrical and topological values of a series of DPP pharmacophores. The newly synthesized pharmacophores were tested for their antagonist activities by: (1) inhibition of (N-methyl-/sup 3/H)scopolamine binding assay to the muscarinic receptors of N4TG1 neuroblastoma cells; (2) blocking of acetylcholine-induced contraction of guinea pig ileum; and (3) inhibition of carbachol-induced ..cap alpha..-amylase release from rat pancreas. The differences in the log of these biological activities were directly and significantly related to the distancesmore » between the carbonyl oxygen of the DPP and the quaternary nitrogen of the modified pharmacophores. The biological activities, while depending on each particular assay, varied between three and four logs of activity. The charge remained the same in all the pharmacophores. There were no QSAR correlations between molecular volume, molecular connectivity, or principle moments and their antagonistic activities, although multivariate QSAR was not employed. Thus, based on distance geometry, potent muscarinic pharmacophores can be predicted.« less

Structural and Immunological Activity Characterization of a Polysaccharide Isolated from Meretrix meretrix Linnaeus

PubMed Central

Li, Li; Li, Heng; Qian, Jianying; He, Yongfeng; Zheng, Jialin; Lu, Zhenming; Xu, Zhenghong; Shi, Jinsong

2015-01-01

Polysaccharides from marine clams perform various biological activities, whereas information on structure is scarce. Here, a water-soluble polysaccharide MMPX-B2 was isolated from Meretrix meretrix Linnaeus. The proposed structure was deduced through characterization and its immunological activity was investigated. MMPX-B2 consisted of d-glucose and d-galctose residues at a molar ratio of 3.51:1.00. The average molecular weight of MMPX-B2 was 510 kDa. This polysaccharide possessed a main chain of (1→4)-linked-α-d-glucopyranosyl residues, partially substituted at the C-6 position by a few terminal β-d-galactose residues or branched chains consisting of (1→3)-linked β-d-galactose residues. Preliminary immunological tests in vitro showed that MMPX-B2 could stimulate the murine macrophages to release various cytokines, and the structure-activity relationship was then established. The present study demonstrated the potential immunological activity of MMPX-B2, and provided references for studying the active ingredients in M. meretrix. PMID:26729136

2-Guanidino-quinazolines as a novel class of translation inhibitors.

PubMed

Komarova Andreyanova, E S; Osterman, I A; Pletnev, P I; Ivanenkov, Y A; Majouga, A G; Bogdanov, A A; Sergiev, P V

2017-02-01

A variety of structurally unrelated organic compounds has been reported to have antibacterial activity. Among these, certain small-molecule translation inhibitors have attracted a great deal of attention, due to their relatively high selectivity against prokaryotes, and an appropriate therapeutic index with minor "off target" effects. However, ribosomes are being considered as poorly druggable biological targets, thereby making some routine computational-based approaches to rational drug design and its development rather ineffective. Taking this into account, diversity-oriented biological screening can reasonably be considered as the most advantageous strategy. Thus, using a high-throughput screening (HTS) platform, we applied a unique biological assay for in vitro evaluation of thousands of organic molecules, especially targeted against bacterial ribosomes and translation. As a result, we have identified a series of structurally diverse small-molecule compounds that induce a reporter strain sensitive to translation and DNA biosynthesis inhibitors. In a cell free system, several molecules were found to strongly inhibit protein biosynthesis. Among them, compounds bearing a 2-guanidino-quinazoline core demonstrated the most promising antibacterial activity. With regard to the preliminary structure-activity relationship (SAR) study, we revealed that relatively small substituents at positions 4, 6 and 8 of the quinazoline ring significantly enhance the target activity whereas modification of the guanidine group leads to decrease or loss of antibacterial potency. This novel class of translation inhibitors can properly be regarded as a promising starting point for the development of novel antibacterial therapeutic or screening tools. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Advances on Bioactive Polysaccharides from Medicinal Plants.

PubMed

Xie, Jian-Hua; Jin, Ming-Liang; Morris, Gordon A; Zha, Xue-Qiang; Chen, Han-Qing; Yi, Yang; Li, Jing-En; Wang, Zhi-Jun; Gao, Jie; Nie, Shao-Ping; Shang, Peng; Xie, Ming-Yong

2016-07-29

In recent decades, the polysaccharides from the medicinal plants have attracted a lot of attention due to their significant bioactivities, such as anti-tumor activity, antioxidant activity, anticoagulant activity, antidiabetic activity, radioprotection effect, anti-viral activity, hypolipidemic and immunomodulatory activities, which make them suitable for medicinal applications. Previous studies have also shown that medicinal plant polysaccharides are non-toxic and show no side effects. Based on these encouraging observations, most researches have been focusing on the isolation and identification of polysaccharides, as well as their bioactivities. A large number of bioactive polysaccharides with different structural features and biological effects from medicinal plants have been purified and characterized. This review provides a comprehensive summary of the most recent developments in physiochemical, structural features and biological activities of bioactive polysaccharides from a number of important medicinal plants, such as polysaccharides from Astragalus membranaceus, Dendrobium plants, Bupleurum, Cactus fruits, Acanthopanax senticosus, Angelica sinensis (Oliv.) Diels, Aloe barbadensis Miller, and Dimocarpus longan Lour. Moreover, the paper has also been focused on the applications of bioactive polysaccharides for medicinal applications. Recent studies have provided evidence that polysaccharides from medicinal plants can play a vital role in bioactivities. The contents and data will serve as a useful reference material for further investigation, production, and application of these polysaccharides in functional foods and therapeutic agents.

Saponins from sea cucumber and their biological activities.

PubMed

Zhao, Yingcai; Xue, Changhu; Zhang, Tiantian; Wang, YuMing

2018-06-22

Sea cucumbers, belonging to the phylum Echinodermata, have been valued for centuries as a nutritious and functional food with various bioactivities. Sea cucumbers can produce highly active substances, notably saponins, the main secondary metabolites, which are the basis of their chemical defense. The saponins are mostly triterpene glycosides with triterpenes or steroid in aglycone, which possess multiple biological properties including anti-tumor, hypolipidemic activity, improvement of nonalcoholic fatty liver, inhibition of fat accumulation, anti-hyperuricemia, promotion of bone marrow hematopoiesis, anti-hypertension, etc. Sea cucumber saponins have received attention due to their rich sources, low toxicity, high efficiency, and few side effects. This review summarizes current research on the structure and activities of sea cucumber saponins based on the physiological and pharmacological activities from source, experimental models, efficacy and mechanisms, which may provide a valuable reference for the development of sea cucumber saponins.

Antimalarial agents against both sexual and asexual parasites stages: structure-activity relationships and biological studies of the Malaria Box compound 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine (MMV019918) and analogues.

PubMed

Vallone, Alessandra; D'Alessandro, Sarah; Brogi, Simone; Brindisi, Margherita; Chemi, Giulia; Alfano, Gloria; Lamponi, Stefania; Lee, Soon Goo; Jez, Joseph M; Koolen, Karin J M; Dechering, Koen J; Saponara, Simona; Fusi, Fabio; Gorelli, Beatrice; Taramelli, Donatella; Parapini, Silvia; Caldelari, Reto; Campiani, Giuseppe; Gemma, Sandra; Butini, Stefania

2018-04-25

Therapies addressing multiple stages of Plasmodium falciparum life cycle are highly desirable for implementing malaria elimination strategies. MMV019918 (1, 1-[5-(4-bromo-2-chlorophenyl)furan-2-yl]-N-[(piperidin-4-yl)methyl]methanamine) was selected from the MMV Malaria Box for its dual activity against both asexual stages and gametocytes. In-depth structure-activity relationship studies and cytotoxicity evaluation led to the selection of 25 for further biological investigation. The potential transmission blocking activity of 25 versus P. falciparum was confirmed through the standard membrane-feeding assay. Both 1 and 25 significantly prolonged atrioventricular conduction time in Langendorff-isolated rat hearts, and showed inhibitory activity of Ba 2+ current through Ca v 1.2 channels. An in silico target-fishing study suggested the enzyme phosphoethanolamine methyltransferase (PfPMT) as a potential target. However, compound activity against PfPMT did not track with the antiplasmodial activity, suggesting the latter activity relies on a different molecular target. Nevertheless, 25 showed interesting activity against PfPMT, which could be an important starting point for the identification of more potent inhibitors active against both sexual and asexual stages of the parasite. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Morphological communication: exploiting coupled dynamics in a complex mechanical structure to achieve locomotion

PubMed Central

Rieffel, John A.; Valero-Cuevas, Francisco J.; Lipson, Hod

2010-01-01

Traditional engineering approaches strive to avoid, or actively suppress, nonlinear dynamic coupling among components. Biological systems, in contrast, are often rife with these dynamics. Could there be, in some cases, a benefit to high degrees of dynamical coupling? Here we present a distributed robotic control scheme inspired by the biological phenomenon of tensegrity-based mechanotransduction. This emergence of morphology-as-information-conduit or ‘morphological communication’, enabled by time-sensitive spiking neural networks, presents a new paradigm for the decentralized control of large, coupled, modular systems. These results significantly bolster, both in magnitude and in form, the idea of morphological computation in robotic control. Furthermore, they lend further credence to ideas of embodied anatomical computation in biological systems, on scales ranging from cellular structures up to the tendinous networks of the human hand. PMID:19776146

Semisynthesis, Characterization and Evaluation of New Adenosine Derivatives as Antiproliferative Agents.

PubMed

Valdés Zurita, Francisco; Brown Vega, Nelson; Gutiérrez Cabrera, Margarita

2018-05-08

We describe the semisynthesis and biological effects of adenosine derivatives, which were anticipated to function as agonists for the A₃ receptor. Molecular docking was used to select candidate compounds. Fifteen nucleoside derivatives were obtained through nucleophilic substitutions of the N ⁶-position of the nucleoside precursor 6-chloropurine riboside by amines of different origin. All compounds were purified by column chromatography and further characterized by spectroscopic and spectrometric techniques, showing moderate yield. These molecules were then evaluated for their antiproliferative activity in human gastric cancer cells expressing the A₃ receptor. We found that the compounds obtained have antiproliferative activity and that new structural modifications can enhance their biological activity. The ADME (Absorption, Distribution, Metabolism and Excretion) properties of the most active compounds were also evaluated theoretically.

Orientation determination of interfacial beta-sheet structures in situ.

PubMed

Nguyen, Khoi Tan; King, John Thomas; Chen, Zhan

2010-07-01

Structural information such as orientations of interfacial proteins and peptides is important for understanding properties and functions of such biological molecules, which play crucial roles in biological applications and processes such as antimicrobial selectivity, membrane protein activity, biocompatibility, and biosensing performance. The alpha-helical and beta-sheet structures are the most widely encountered secondary structures in peptides and proteins. In this paper, for the first time, a method to quantify the orientation of the interfacial beta-sheet structure using a combined attenuated total reflectance Fourier transformation infrared spectroscopic (ATR-FTIR) and sum frequency generation (SFG) vibrational spectroscopic study was developed. As an illustration of the methodology, the orientation of tachyplesin I, a 17 amino acid peptide with an antiparallel beta-sheet, adsorbed to polymer surfaces as well as associated with a lipid bilayer was determined using the regular and chiral SFG spectra, together with polarized ATR-FTIR amide I signals. Both the tilt angle (theta) and the twist angle (psi) of the beta-sheet at interfaces are determined. The developed method in this paper can be used to obtain in situ structural information of beta-sheet components in complex molecules. The combination of this method and the existing methodology that is currently used to investigate alpha-helical structures will greatly broaden the application of optical spectroscopy in physical chemistry, biochemistry, biophysics, and structural biology.

Redox-signals and macrophage biology (for the upcoming issue of molecular aspects of medicine on signaling by reactive oxygen species).

PubMed

Weigert, Andreas; von Knethen, Andreas; Fuhrmann, Dominik; Dehne, Nathalie; Brüne, Bernhard

2018-01-11

Macrophages are known for their versatile role in biology. They sense and clear structures that contain exogenous or endogenous pathogen-associated molecular patterns. This process is tightly linked to the production of a mixture of potentially harmful oxidants and cytokines. Their inherent destructive behavior is directed against foreign material or structures of 'altered self', which explains the role of macrophages during innate immune reactions and inflammation. However, there is also another side of macrophages when they turn into a tissue regenerative, pro-resolving, and healing phenotype. Phenotype changes of macrophages are termed macrophage polarization, representing a continuum between classical and alternative activation. Macrophages as the dominating producers of superoxide/hydrogen peroxide and nitric oxide are not only prone to oxidative modifications but also to more subtle signaling properties of redox-active molecules conveying redox regulation. We review basic concepts of the enzymatic nitric oxide and superoxide production within macrophages, refer to their unique chemical reactions and outline biological consequences not only for macrophage biology but also for their communication with cells in the microenvironment. These considerations link hypoxia to the NO system, addressing feedforward as well as feedback circuits. Moreover, we summarize the role of redox-signaling affecting epigenetics and reflect the central role of mitochondrial-derived oxygen species in inflammation. To better understand the diverse functions of macrophages during initiation as well as resolution of inflammation and to decode their versatile roles during innate and adaptive immunity with the entire spectrum of cell protective towards cell destructive activities we need to appreciate the signaling properties of redox-active species. Herein we discuss macrophage responses in terms of nitric oxide and superoxide formation with the modulating impact of hypoxia. Copyright © 2018. Published by Elsevier Ltd.

Anti-inflammatory, antiproliferative, and cytoprotective activity of NO chimera nitrates of use in cancer chemoprevention.

PubMed

Hagos, Ghenet K; Abdul-Hay, Samer O; Sohn, Johann; Edirisinghe, Praneeth D; Chandrasena, R Esala P; Wang, Zhiqiang; Li, Qian; Thatcher, Gregory R J

2008-11-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown promise in colorectal cancer (CRC), but they are compromised by gastrotoxicity. NO-NSAIDs are hybrid nitrates conjugated to an NSAID designed to exploit the gastroprotective properties of NO bioactivity. The NO chimera ethyl 2-((2,3-bis(nitrooxy)propyl)disulfanyl)benzoate (GT-094), a novel nitrate containing an NSAID and disulfide pharmacophores, is effective in vivo in rat models of CRC and is a lead compound for design of agents of use in CRC. Preferred chemopreventive agents possess 1) antiproliferative and 2) anti-inflammatory actions and 3) the ability to induce cytoprotective phase 2 enzymes. To determine the contribution of each pharmacophore to the biological activity of GT-094, these three biological activities were studied in vitro in compounds that deconstructed the structural elements of the lead GT-094. The anti-inflammatory and antiproliferative actions of GT-094 in vivo were recapitulated in vitro, and GT-094 was seen to induce phase 2 enzymes via the antioxidant responsive element. In the variety of colon, macrophage-like, and liver cell lines studied, the evidence from structure-activity relationships was that the disulfide structural element of GT-094 is the dominant contributor in vitro to the anti-inflammatory activity, antiproliferation, and enzyme induction. The results provide a direction for lead compound refinement. The evidence for a contribution from the NO mimetic activity of nitrates in vitro was equivocal, and combinations of nitrates with acetylsalicylic acid were inactive.

On the structural affinity of macromolecules with different biological properties: molecular dynamics simulations of a series of TEM-1 mutants.

PubMed

Giampaolo, Alessia Di; Mazza, Fernando; Daidone, Isabella; Amicosante, Gianfranco; Perilli, Mariagrazia; Aschi, Massimiliano

2013-07-12

Molecular Dynamics simulations have been carried out in order to provide a molecular rationalization of the biological and thermodynamic differences observed for a class of TEM β-lactamases. In particular we have considered the TEM-1(wt), the single point mutants TEM-40 and TEM-19 representative of IRT and ESBL classes respectively, and TEM-1 mutant M182T, TEM-32 and TEM-20 which differ from the first three for the additional of M182T mutation. Results indicate that most of the thermodynamic, and probably biological behaviour of these systems arise from subtle effects which, starting from the alterations of the local interactions, produce drastic modifications of the conformational space spanned by the enzymes. The present study suggests that systems showing essentially the same secondary and tertiary structure may differentiate their chemical-biological activity essentially (and probably exclusively) on the basis of the thermal fluctuations occurring in their physiological environment. Copyright © 2013 Elsevier Inc. All rights reserved.

Synthesis, structural elucidation, biological, antioxidant and nuclease activities of some 5-Fluorouracil-amino acid mixed ligand complexes

NASA Astrophysics Data System (ADS)

Shobana, Sutha; Subramaniam, Perumal; Mitu, Liviu; Dharmaraja, Jeyaprakash; Arvind Narayan, Sundaram

2015-01-01

Some biologically active mixed ligand complexes (1-9) have been synthesized from 5-Fluorouracil (5-FU; A) and amino acids (B) such as glycine (gly), L-alanine (ala) and L-valine (val) with Ni(II), Cu(II) and Zn(II) ions. The synthesized mixed ligand complexes (1-9) were characterized by various physico-chemical, spectral, thermal and morphological studies. 5-Fluorouracil and its mixed ligand complexes have been tested for their in vitro biological activities against some pathogenic bacterial and fungal species by the agar well diffusion method. The in vitro antioxidant activities of 5-Fluorouracil and its complexes have also been investigated by using the DPPH assay method. The results demonstrate that Cu(II) mixed ligand complexes (4-6) exhibit potent biological as well as antioxidant activities compared to 5-Fluorouracil and Ni(II) (1-3) and Zn(II) (7-9) mixed ligand complexes. Further, the cleaving activities of CT DNA under aerobic conditions show moderate activity with the synthesized Cu(II) and Ni(II) mixed ligand complexes (1-6) while no activity is seen with Zn(II) complexes (7-9). Binding studies of CT DNA with these complexes show a decrease in intensity of the charge transfer band to the extent of 5-15% along with a minor red shift. The free energy change values (Δ‡G) calculated from intrinsic binding constants indicate that the interaction between mixed ligand complex and DNA is spontaneous.

A Way Forward Commentary

EPA Science Inventory

Models for predicting adverse outcomes can help reduce and focus animal testing with new and existing chemicals. This short "thought starter" describes how quantitative-structure activity relationship and systems biology models can be used to help define toxicity pathways and li...

Characterization of two peptides isolated from the venom of social wasp Chartergellus communis (Hymenoptera: Vespidae): Influence of multiple alanine residues and C-terminal amidation on biological effects.

PubMed

Lopes, Kamila Soares; Campos, Gabriel Avohay Alves; Camargo, Luana Cristina; de Souza, Adolfo Carlos Barros; Ibituruna, Beatriz Vasconcelos; Magalhães, Ana Carolina Martins; da Rocha, Lucas Ferreira; Garcia, Alessa Bembom; Rodrigues, Mosar Correa; Ribeiro, Dagon Manoel; Costa, Michelle Cruz; López, Manuel Humberto Mera; Nolli, Luciana Marangni; Zamudio-Zuniga, Fernando; Possani, Lourival Domingos; Schwartz, Elisabeth Ferroni; Mortari, Márcia Renata

2017-09-01

Chatergellus communis is a wasp species endemic to the neotropical region and its venom constituents have never been described. In this study, two peptides from C. communis venom, denominated Communis and Communis-AAAA, were chemically and biologically characterized. In respect to the chemical characterization, the following amino acid sequences and molecular masses were identified: Communis: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-COOH (1340.9Da) Communis-AAAA: Ile-Asn-Trp-Lys-Ala-Ile-Leu-Gly-Lys-Ile-Gly-Lys-Ala-Ala-Ala-Ala-Val-Xle-NH 2 (1836.3Da). Furthermore, their biological effects were compared, accounting for the differences in structural characteristics between the two peptides. To this end, three biological assays were performed in order to evaluate the hyperalgesic, edematogenic and hemolytic effects of these molecules. Communis-AAAA, unlike Communis, showed a potent hemolytic activity with EC 50 =142.6μM. Moreover, the highest dose of Communis-AAAA (2nmol/animal) induced hyperalgesia in mice. On the other hand, Communis (10nmol/animal) was able to induce edema but did not present hemolytic or hyperalgesic activity. Although both peptides have similarities in linear structures, we demonstrated the distinct biological effects of Communis and Communis-AAAA. This is the first study with Chartegellus communis venom, and both Communis and Communis-AAAA are unpublished peptides. Copyright © 2017 Elsevier Inc. All rights reserved.

Arrangement of RecA protein in its active filament determined by polarized-light spectroscopy.

PubMed

Morimatsu, Katsumi; Takahashi, Masayuki; Nordén, Bengt

2002-09-03

Linear dichroism (LD) polarized-light spectroscopy is used to determine the arrangement of RecA in its large filamentous complex with DNA, active in homologous recombination. Angular orientation data for two tryptophan and seven tyrosine residues, deduced from differential LD of wild-type RecA vs. mutants that were engineered to attenuate the UV absorption of selected residues, revealed a rotation by some 40 degrees of the RecA subunits relative to the arrangement in crystal without DNA. In addition, conformational changes are observed for tyrosine residues assigned to be involved in DNA binding and in RecA-RecA contacts, thus potentially related to the global structure of the filament and its biological function. The presented spectroscopic approach, called "Site-Specific Linear Dichroism" (SSLD), may find forceful applications also to other biologically important fibrous complexes not amenable to x-ray crystallographic or NMR structural analysis.

Structure and Function of Viral Deubiquitinating Enzymes.

PubMed

Bailey-Elkin, Ben A; Knaap, Robert C M; Kikkert, Marjolein; Mark, Brian L

2017-11-10

Post-translational modification of cellular proteins by ubiquitin regulates numerous cellular processes, including innate and adaptive immune responses. Ubiquitin-mediated control over these processes can be reversed by cellular deubiquitinating enzymes (DUBs), which remove ubiquitin from cellular targets and depolymerize polyubiquitin chains. The importance of protein ubiquitination to host immunity has been underscored by the discovery of viruses that encode proteases with deubiquitinating activity, many of which have been demonstrated to actively corrupt cellular ubiquitin-dependent processes to suppress innate antiviral responses and promote viral replication. DUBs have now been identified in diverse viral lineages, and their characterization is providing valuable insights into virus biology and the role of the ubiquitin system in host antiviral mechanisms. Here, we provide an overview of the structural biology of these fascinating viral enzymes and their role innate immune evasion and viral replication. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fungal phytotoxins with potential herbicidal activity: chemical and biological characterization.

PubMed

Cimmino, Alessio; Masi, Marco; Evidente, Marco; Superchi, Stefano; Evidente, Antonio

2015-12-19

Covering: 2007 to 2015 Fungal phytotoxins are secondary metabolites playing an important role in the induction of disease symptoms interfering with host plant physiological processes. Although fungal pathogens represent a heavy constraint for agrarian production and for forest and environmental heritage, they can also represent an ecofriendly alternative to manage weeds. Indeed, the phytotoxins produced by weed pathogenic fungi are an efficient tool to design natural, safe bioherbicides. Their use could avoid that of synthetic pesticides causing resistance in the host plants and the long term impact of residues in agricultural products with a risk to human and animal health. The isolation and structural and biological characterization of phytotoxins produced by pathogenic fungi for weeds, including parasitic plants, are described. Structure activity relationships and mode of action studies for some phytotoxins are also reported to elucidate the herbicide potential of these promising fungal metabolites.

Cocrystals of caffeine with formylphenoxyaliphatic acids: Syntheses, structural characterization, and biological activity

NASA Astrophysics Data System (ADS)

Suresh Kumar, G. S.; Seethalakshmi, P. G.; Bhuvanesh, N.; Kumaresan, S.

2013-02-01

Three organic cocrystals namely, caffeine:p-formylphenoxyacetic acid [(caf)(p-fpaa)] (1) caffeine:o-formylphenoxyacetic acid monohydrate [(caf)(o-fpaa)]H2O (2) and caffeine:p-formylphenoxypropionic acid [(caf)(p-fppa)] (3) were synthesized and studied by FT-IR, NMR, and single crystal XRD studies. The crystal system of cocrystal [(caf)(p-fpaa)] (1) is monoclinic with space group P21/n and Z = 16, that of cocrystal [(caf)(o-fpaa)]H2O (2) is triclinic with space group P - 1 and Z = 2, and that of cocrystal [(caf)(p-fppa)] (3) is monoclinic with space group P21/c and Z = 4. The imidazole-carboxylic acid synthon is observed in all the three cocrystals. The intermolecular hydrogen bonds, Osbnd H···N and π-π interactions together play a major role in stabilizing the crystal structure of all the three cocrystals. The biological activities of crystals 1-3 were studied.

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

PubMed

Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

2017-08-24

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

New Method for Producing Significant Amounts of RNA Labeled at Specific Sites | Center for Cancer Research

Cancer.gov

Among biomacromolecules, RNA is the most versatile, and it plays indispensable roles in almost all aspects of biology. For example, in addition to serving as mRNAs coding for proteins, RNAs regulate gene expression, such as controlling where, when, and how efficiently a gene gets expressed, participate in RNA processing, encode the genetic information of some viruses, serve as scaffolds, and even possess enzymatic activity. To study these RNAs and their biological functions and to make use of those RNA activities for biomedical applications, researchers first need to make various types of RNA. For structural biologists incorporating modified or labeled nucleotides at specific sites in RNA molecules of interest is critical to gain structural insight into RNA functions. However, placing labeled or modified residue(s) in desired positions in a large RNA has not been possible until now.

The role of exoproteases in governing intraneuronal metabolism of botulinum toxin.

PubMed

Simpson, Lance L; Maksymowych, Andrew B; Kouguchi, Hirokazu; Dubois, Garrett; Bora, Roop S; Joshi, Suresh

2005-04-01

Botulinum toxin type A has a long duration of action, and thus it can block transmitter release for several weeks to several months. However, little is known about the precise mechanism that accounts for termination of toxin action. Therefore, experiments were done to gauge the effects of aminopeptidases and carboxypeptidases on the structure and function of the toxin. Exoproteases were added to the holotoxin, the native light chain, and a recombinant light chain. Treated toxin and light chain were examined for their effects on neuromuscular transmission and on isolated substrate. The data showed that aminopeptidase attack did not alter the N-terminus of the toxin/light chain, nor did it produce losses in biological activity. Carboxypeptidase attack did alter the C-terminus of the light chain, but not sufficiently to alter biological activity. The data suggest that the tertiary structure of the light chain confers upon the molecule substantial resistance to exoproteases.

Enhanced reaction kinetics in biological cells

NASA Astrophysics Data System (ADS)

Loverdo, C.; Bénichou, O.; Moreau, M.; Voituriez, R.

2008-02-01

The cell cytoskeleton is a striking example of an `active' medium driven out-of-equilibrium by ATP hydrolysis. Such activity has been shown to have a spectacular impact on the mechanical and rheological properties of the cellular medium, as well as on its transport properties: a generic tracer particle freely diffuses as in a standard equilibrium medium, but also intermittently binds with random interaction times to motor proteins, which perform active ballistic excursions along cytoskeletal filaments. Here, we propose an analytical model of transport-limited reactions in active media, and show quantitatively how active transport can enhance reactivity for large enough tracers such as vesicles. We derive analytically the average interaction time with motor proteins that optimizes the reaction rate, and reveal remarkable universal features of the optimal configuration. We discuss why active transport may be beneficial in various biological examples: cell cytoskeleton, membranes and lamellipodia, and tubular structures such as axons.

Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy

PubMed Central

Fox, Christopher B.; Barnes V, Lucien; Evers, Tara; Chesko, James D.; Vedvick, Thomas S.; Coler, Rhea N.; Reed, Steven G.; Baldwin, Susan L.

2012-01-01

Please cite this paper as: Fox et al. (2012) Adjuvanted pandemic influenza vaccine: variation of emulsion components affects stability, antigen structure, and vaccine efficacy. Influenza and Other Respiratory Viruses DOI: 10.1111/irv.12031. Abstract Background  Adjuvant formulations are critical components of modern vaccines based on recombinant proteins, which are often poorly immunogenic without additional immune stimulants. Oil‐in‐water emulsions comprise an advanced class of vaccine adjuvants that are components of approved seasonal and pandemic influenza vaccines. However, few reports have been published that systematically evaluate the in vitro stability and in vivo adjuvant effects of different emulsion components. Objectives  To evaluate distinct classes of surfactants, oils, and excipients, for their effects on emulsion particle size stability, antigen structural interactions, and in vivo activity when formulated with a recombinant H5N1 antigen. Methods  Emulsions were manufactured by high pressure homogenization and characterized alone or in the presence of vaccine antigen by dynamic light scattering, zeta potential, viscosity, pH, hemolytic activity, electron microscopy, fluorescence spectroscopy, and SDS‐PAGE. In vivo vaccine activity in the murine model was characterized by measuring antibody titers, antibody‐secreting plasma cells, hemagglutination inhibition titers, and cytokine production. Results  We demonstrate that surfactant class and presence of additional excipients are not critical for biological activity, whereas oil structure is crucial. Moreover, we report that simplified two‐component emulsions appear more stable by particle size than more complex formulations.Finally, differences in antigen structural interactions with the various emulsions do not appear to correlate with in vivo activity. Conclusions  Oil‐in‐water emulsions can significantly enhance antibody and cellular immune responses to a pandemic influenza antigen. The dramatic differences in adjuvant activity between squalene‐based emulsion and medium chain triglyceride‐based emulsion are due principally to the biological activity of the oil composition rather than physical interactions of the antigen with the emulsion. PMID:23122325

Studies of the structure-activity relationships of peptides and proteins involved in growth and development based on their three-dimensional structures.

PubMed

Nagata, Koji

2010-01-01

Peptides and proteins with similar amino acid sequences can have different biological functions. Knowledge of their three-dimensional molecular structures is critically important in identifying their functional determinants. In this review, I describe the results of our and other groups' structure-based functional characterization of insect insulin-like peptides, a crustacean hyperglycemic hormone-family peptide, a mammalian epidermal growth factor-family protein, and an intracellular signaling domain that recognizes proline-rich sequence.

Preparation and Characterization of Biofunctionalized Inorganic Substrates.

PubMed

Dugger, Jason W; Webb, Lauren J

2015-09-29

Integrating the function of biological molecules into traditional inorganic materials and substrates couples biologically relevant function to synthetic devices and generates new materials and capabilities by combining biological and inorganic functions. At this so-called "bio/abio interface," basic biological functions such as ligand binding and catalysis can be co-opted to detect analytes with exceptional sensitivity or to generate useful molecules with chiral specificity under entirely benign reaction conditions. Proteins function in dynamic, complex, and crowded environments (the living cell) and are therefore appropriate for integrating into multistep, multiscale, multimaterial devices such as integrated circuits and heterogeneous catalysts. However, the goal of reproducing the highly specific activities of biomolecules in the perturbed chemical and electrostatic environment at an inorganic interface while maintaining their native conformations is challenging to achieve. Moreover, characterizing protein structure and function at a surface is often difficult, particularly if one wishes to compare the activity of the protein to that of the dilute, aqueous solution phase. Our laboratory has developed a general strategy to address this challenge by taking advantage of the structural and chemical properties of alkanethiol self-assembled monolayers (SAMs) on gold surfaces that are functionalized with covalently tethered peptides. These surface-bound peptides then act as the chemical recognition element for a target protein, generating a biomimetic surface in which protein orientation, structure, density, and function are controlled and variable. Herein we discuss current research and future directions related to generating a chemically tunable biofunctionalization strategy that has potential to successfully incorporate the highly specialized functions of proteins onto inorganic substrates.

[Biologics - nomenclature and classification].

PubMed

Eichbaum, Christine; Haefeli, Walter E

2011-11-01

Biological medicines are a heterogeneous group of drugs that are produced by living organisms using genetic or biological technology. Unlike chemically derived small molecules biologics are structurally complex making characterization and manufacturing difficult. Moreover, biological medicines show a great variety concerning their clinical use. To appropriately consider these particularities, there are other standards and guidelines for approval of similar derivatives of biologics, the so-called biosimilars or follow-on biologics. In contrast to a generic medicinal product containing a chemically identical active ingredient, a biosimilar is only expected to be similar to the innovator drug. Nowadays, monoclonal antibodies, fragments of antibodies, and fusion proteins manufactured by recombinant procedures play an important role. They have been used in many specialties for diagnostic and therapeutic purposes and are subject to continuous further development and improvement. Their nomenclature is based on a classification by the WHO which allows drawing conclusions for class of substance, origin, and pharmacological target.

Modelling non-Euclidean movement and landscape connectivity in highly structured ecological networks

USGS Publications Warehouse

Sutherland, Christopher; Fuller, Angela K.; Royle, J. Andrew

2015-01-01

The ecological distance SCR model uses spatially indexed capture-recapture data to estimate how activity patterns are influenced by landscape structure. As well as reducing bias in estimates of abundance, this approach provides biologically realistic representations of home range geometry, and direct information about species-landscape interactions. The incorporation of both structural (landscape) and functional (movement) components of connectivity provides a direct measure of species-specific landscape connectivity.

Synthesis and structure-activity relationships of carbohydrazides and 1,3,4-oxadiazole derivatives bearing imidazolidine moiety against the yellow fever and dengue vector, Aedes aegypti

USDA-ARS?s Scientific Manuscript database

BACKGROUND: 1,3,4-oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3-(methylsulfonyl)-2-oxoimidazolidine-1-carbonyl chloride and screened...

The study on molecular structure and microbiological activity of alkali metal 3-hydroxyphenylycetates

NASA Astrophysics Data System (ADS)

Samsonowicz, M.; Regulska, E.; Kowczyk-Sadowy, M.; Butarewicz, A.; Lewandowski, W.

2017-10-01

The biological activity of chemical compounds depends on their molecular structure. In this paper molecular structure of 3-hydroxyphenylacetates in comparison to 3-hydroxyphenylacetic acid was studied. FT-IR, FT-Raman and NMR spectroscopy and density functional theory (DFT) calculations was used. The B3LYP/6-311++G(d,p) hybrid functional method was used to calculate optimized geometrical structures of studied compounds. The Mulliken, APT, MK, ChelpG and NBO atomic charges as well as dipole moment and energy values were calculated. Theoretical chemical shifts in NMR spectra and the wavenumbers and intensities of the bands in vibrational spectra were analyzed. Calculated parameters were compared to experimental characteristic of studied compounds. Microbiological analysis of studied compounds was performed relative to: Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Klebsiella oxytoca. The relationship between spectroscopic and structure parameters of studied compounds in regard to their activity was analyzed.