Relevant bibliographies by topics / Ligand binding interactions

Academic literature on the topic 'Ligand binding interactions'

Author: Grafiati
Published: 10 December 2022
Last updated: 29 January 2023

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Contents

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Ligand binding interactions.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Ligand binding interactions"

1

Marsh, Lorraine. "Strong Ligand-Protein Interactions Derived from Diffuse Ligand Interactions with Loose Binding Sites." BioMed Research International 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/746980.

Full text
Abstract:
Many systems in biology rely on binding of ligands to target proteins in a single high-affinity conformation with a favorableΔG. Alternatively, interactions of ligands with protein regions that allow diffuse binding, distributed over multiple sites and conformations, can exhibit favorableΔGbecause of their higher entropy. Diffuse binding may be biologically important for multidrug transporters and carrier proteins. A fine-grained computational method for numerical integration of total bindingΔGarising from diffuse regional interaction of a ligand in multiple conformations using a Markov Chain Monte Carlo (MCMC) approach is presented. This method yields a metric that quantifies the influence on overall ligand affinity of ligand binding to multiple, distinct sites within a protein binding region. This metric is essentially a measure of dispersion in equilibrium ligand binding and depends on both the number of potential sites of interaction and the distribution of their individual predicted affinities. Analysis of test cases indicates that, for some ligand/protein pairs involving transporters and carrier proteins, diffuse binding contributes greatly to total affinity, whereas in other cases the influence is modest. This approach may be useful for studying situations where “nonspecific” interactions contribute to biological function.
APA, Harvard, Vancouver, ISO, and other styles
2

Leigh, David A. "Summing Up Ligand Binding Interactions." Chemistry & Biology 10, no. 12 (December 2003): 1143–44. http://dx.doi.org/10.1016/j.chembiol.2003.12.006.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Kaiser, Anette, and Irene Coin. "Capturing Peptide–GPCR Interactions and Their Dynamics." Molecules 25, no. 20 (October 15, 2020): 4724. http://dx.doi.org/10.3390/molecules25204724.

Full text
Abstract:
Many biological functions of peptides are mediated through G protein-coupled receptors (GPCRs). Upon ligand binding, GPCRs undergo conformational changes that facilitate the binding and activation of multiple effectors. GPCRs regulate nearly all physiological processes and are a favorite pharmacological target. In particular, drugs are sought after that elicit the recruitment of selected effectors only (biased ligands). Understanding how ligands bind to GPCRs and which conformational changes they induce is a fundamental step toward the development of more efficient and specific drugs. Moreover, it is emerging that the dynamic of the ligand–receptor interaction contributes to the specificity of both ligand recognition and effector recruitment, an aspect that is missing in structural snapshots from crystallography. We describe here biochemical and biophysical techniques to address ligand–receptor interactions in their structural and dynamic aspects, which include mutagenesis, crosslinking, spectroscopic techniques, and mass-spectrometry profiling. With a main focus on peptide receptors, we present methods to unveil the ligand–receptor contact interface and methods that address conformational changes both in the ligand and the GPCR. The presented studies highlight a wide structural heterogeneity among peptide receptors, reveal distinct structural changes occurring during ligand binding and a surprisingly high dynamics of the ligand–GPCR complexes.
APA, Harvard, Vancouver, ISO, and other styles
4

Langelaan, David N., and Jan K. Rainey. "Membrane catalysis of peptide–receptor bindingThis paper is one of a selection of papers published in this special issue entitled “Canadian Society of Biochemistry, Molecular & Cellular Biology 52nd Annual Meeting — Protein Folding: Principles and Diseases” and has undergone the Journal's usual peer review process." Biochemistry and Cell Biology 88, no. 2 (April 2010): 203–10. http://dx.doi.org/10.1139/o09-129.

Full text
Abstract:
The membrane catalysis hypothesis states that a peptide ligand activates its target receptor after an initial interaction with the surrounding membrane. Upon membrane binding and interaction, the ligand is structured such that receptor binding and activation is encouraged. As evidence for this hypothesis, there are numerous studies concerning the conformation that peptides adopt in membrane mimetic environments. This mini-review analyzes the features of ligand peptides with an available high-resolution membrane-induced structure and a characterized membrane-binding region. At the peptide–membrane interface, both amphipathic helices and turn structures are commonly formed in peptide ligands and both hydrophobic and electrostatic interactions can be responsible for membrane binding. Apelin is the ligand to the G-protein coupled receptor (GPCR) named APJ, with various important physiological effects, which we have recently characterized both in solution and bound to anionic micelles. The structural changes that apelin undergoes when binding to micelles provide strong evidence for membrane catalysis of apelin–APJ interactions.
APA, Harvard, Vancouver, ISO, and other styles
5

Tozer, Eileen Collins, Paul E. Hughes, and Joseph C. Loftus. "Ligand binding and affinity modulation of integrins." Biochemistry and Cell Biology 74, no. 6 (December 1, 1996): 785–98. http://dx.doi.org/10.1139/o96-085.

Full text
Abstract:
Integrins are cell adhesion receptors that mediate cell–cell and cell–extracellular matrix interactions. The extracellular domains of these receptors possess binding sites for a diverse range of protein ligands. Ligand binding is divalent cation dependent and involves well-defined motifs in the ligand. Integrins can dynamically regulate their affinity for ligands (inside-out signaling). This ability to rapidly modulate their affinity state is key to their involvement in such processes as cell migration and platelet aggregation. This review will focus on two aspects of integrin function: first, on the molecular basis of ligand–integrin interactions and, second, on the underlying mechanisms controlling the affinity state of integrins for their ligands.Key words: integrins, ligand binding, affinity modulation.
APA, Harvard, Vancouver, ISO, and other styles
6

Sharma, Ankur, Annapoorni Rangarajan, and Rajan R. Dighe. "Antibodies against the extracellular domain of human Notch1 receptor reveal the critical role of epidermal-growth-factor-like repeats 25–26in ligand binding and receptor activation." Biochemical Journal 449, no. 2 (December 14, 2012): 519–30. http://dx.doi.org/10.1042/bj20121153.

Full text
Abstract:
The Notch signalling pathway is implicated in a wide variety of cellular processes throughout metazoan development. Although the downstream mechanism of Notch signalling has been extensively studied, the details of its ligand-mediated receptor activation are not clearly understood. Although the role of Notch ELRs [EGF (epidermal growth factor)-like-repeats] 11–12 in ligand binding is known, recent studies have suggested interactions within different ELRs of the Notch receptor whose significance remains to be understood. Here, we report critical inter-domain interactions between human Notch1 ELRs 21–30 and the ELRs 11–15 that are modulated by calcium. Surface plasmon resonance analysis revealed that the interaction between ELRs 21–30 and ELRs 11–15 is ~10-fold stronger than that between ELRs 11–15 and the ligands. Although there was no interaction between Notch1 ELRs 21–30 and the ligands in vitro, addition of pre-clustered Jagged1Fc resulted in the dissociation of the preformed complex between ELRs 21–30 and 11–15, suggesting that inter-domain interactions compete for ligand binding. Furthermore, the antibodies against ELRs 21–30 inhibited ligand binding to the full-length Notch1 and subsequent receptor activation, with the antibodies against ELRs 25–26 being the most effective. These results suggest that the ELRs 25–26 represent a cryptic ligand-binding site which becomes exposed only upon the presence of the ligand. Thus, using specific antibodies against various domains of the Notch1 receptor, we demonstrate that, although ELRs 11–12 are the principal ligand-binding site, the ELRs 25–26 serve as a secondary binding site and play an important role in receptor activation.
APA, Harvard, Vancouver, ISO, and other styles
7

Urien, S., P. Nguyen, S. Berlioz, F. Brée, F. Vacherot, and J. P. Tillement. "Characterization of discrete classes of binding sites of human serum albumin by application of thermodynamic principles." Biochemical Journal 302, no. 1 (August 15, 1994): 69–72. http://dx.doi.org/10.1042/bj3020069.

Full text
Abstract:
The binding interactions of four ligands differing in acid-base properties with human serum albumin (HSA) were examined as a function of temperature. Binding to HSA decreased with increasing temperature for all four ligands. The bound and free ligand concentrations obtained at different temperatures were satisfactorily fitted to a model that incorporates the effect of temperature as an independent covariable and that directly allows the estimation of the enthalpic and entropic components of the ligand-albumin interaction, along with the precision of this estimation. Using this analysis, the binding of acidic ligands could be resolved into two classes of saturable sites, with the determination of the corresponding number of sites, whereas interpretation of binding data at each isolated temperature allowed only the determination of one saturable plus one non-saturable class of site. The thermodynamic constants indicate that binding of ionizable ligands to HSA involves electrostatic plus hydrophobic interactions, whereas only hydrophobic interactions are involved in binding to a second low-affinity class of site when present. Binding of non-ionizable ligands resembles that of the second class of low-affinity sites of ionizable ligands.
APA, Harvard, Vancouver, ISO, and other styles
8

Katzenellenbogen, J. A., and R. Muthyala. "Interactions of exogenous endocrine active substances with nuclear receptors." Pure and Applied Chemistry 75, no. 11-12 (January 1, 2003): 1797–817. http://dx.doi.org/10.1351/pac200375111797.

Full text
Abstract:
Nuclear receptors function as ligand-regulated transcription factors and modulate the expression of sets of genes in response to varying concentrations of ligands. The ligand modulators can be endogenous metabolites that function as hormones, or they can be exogenous substances, such as pharmaceutical agents or environmental substances of natural or man-made origin, which in some cases can cause endocrine disruption. Ligands modulate nuclear receptor activity by binding to their ligand-binding domains and stabilizing conformations that lead either to transcriptional activation or repression. The ligand-binding pocket is somewhat flexible, and binding affinities can be measured over a 10-million-fold range (i.e., with equilibrium dissociation constant values ranging from ca. 0.01 nM to 100 μM). Thus, it is not surprising that by binding a large variety of structures, some nuclear receptors can appear to be promiscuous; however, when affinity is considered, the binding patterns are more restricted. The spectrum of ligands that bind to the estrogen receptor has been most thoroughly investigated. Those from natural sources include natural products in food, such as soy isoflavones and whole grain lignans, as well as microbial products and components from wood. Aside from pharmaceuticals, man-made estrogen ligands can be found in industrial products, such as alkyl phenols from nonionic detergents, bisphenols from plastics, indicator dye impurities, polymer chemicals, and chlorinated aromatics and pesticides. Exogenous ligands are also known for the androgen and progesterone receptors. While it is possible that endocrine disruption can result from exogenous chemicals acting directly as ligands for the nuclear receptors, endocrine disruption needs to be considered in the broader context; thus, compounds also need to be assessed for their effects at other levels, such as on endogenous hormone production, transport, metabolism, and clearance, and at points in signal transduction cascades that are beyond the ligand-receptor interaction.
APA, Harvard, Vancouver, ISO, and other styles
9

Micovic, Vuk, Milovan Ivanovic, and Ljiljana Dosen-Micovic. "Structural requirements for ligands of the δ-opioid receptor." Journal of the Serbian Chemical Society 74, no. 11 (2009): 1207–17. http://dx.doi.org/10.2298/jsc0911207m.

Full text
Abstract:
The ?-opioid receptor is sensitive to ligand geometry. In order to assist the synthesis of new ?-selective opioid ligands, the structure elements of ?-selective opioid ligands necessary for their effective binding were investigated. The automated docking procedure with a flexible ligand was used to simulate the binding of 17 ?-selective ligands to the ?-receptor. It was found that voluminous N-alkyl groups reduce the binding potency of naltrindole derivatives by preventing the ligands from adopting the preferred conformation in the receptor. This was confirmed by enantiospecific binding of chiral compounds where only one enantiomer adopts the naltrindole-like preferred conformation in the binding pocket. Voluminous groups replacing the hydroxyl group in the 3-hydroxybenzyl fragment of naltrindole analogs reduce the binding potency due to unfavorable steric interactions with the receptor. The two diastereoisomers of the potent ?-opioid ligand SNC80 confirmed the preferred binding conformation and the major receptor-ligand interactions.
APA, Harvard, Vancouver, ISO, and other styles
10

Moldogazieva, Nurbubu T., Daria S. Ostroverkhova, Nikolai N. Kuzmich, Vladimir V. Kadochnikov, Alexander A. Terentiev, and Yuri B. Porozov. "Elucidating Binding Sites and Affinities of ERα Agonists and Antagonists to Human Alpha-Fetoprotein by In Silico Modeling and Point Mutagenesis." International Journal of Molecular Sciences 21, no. 3 (January 30, 2020): 893. http://dx.doi.org/10.3390/ijms21030893.

Full text
Abstract:
Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting a variety of hydrophobic ligands, including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth, which can be attributed to its estrogen-binding ability. Despite AFP having long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP–ligand interaction remains obscure. In our study, we constructed a homology-based 3D model of human AFP (HAFP) with the purpose of molecular docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol), and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on the ligand-docked scoring functions, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity binding sites were located (i) in a tunnel formed within HAFP subdomains IB and IIA and (ii) on the opposite side of the molecule in a groove originating from a cavity formed between domains I and III, while (iii) the third low-affinity binding site was found at the bottom of the cavity. Here, 100 ns molecular dynamics (MD) simulation allowed us to study their geometries and showed that HAFP–estrogen interactions were caused by van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP–antiestrogen binding. Molecular mechanics/Generalized Born surface area (MM/GBSA) rescoring method exploited for estimation of binding free energies (ΔGbind) showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP–ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues, along with two disulfide bonds (Cys224–Cys270 and Cys269–Cys277), have key roles in both HAFP–estrogen and HAFP–antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein–ligand interactions and anticancer therapy strategies based on ERα-binding ligands.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Ligand binding interactions"

1

Wade, R. C. "Ligand-macromolecule interactions." Thesis, University of Oxford, 1988. http://ora.ox.ac.uk/objects/uuid:576ce119-6a93-4eb0-a7e4-1f2513736dbd.

Full text
Abstract:
The optimisation of ligand-macromolecule interactions is fundamental to the design of therapeutic agents. The GRID method is a procedure for determining energetically favourable ligand binding sites on molecules of known structure using an empirical energy potential. In this thesis, it has been extended, tested, and then applied to the design of anti-influenza agents. In the GRID method, the energy of a hydrogen-bond is determined by a function which is dependent on the length of the hydrogen-bond, its orientation at the hydrogen-bond donor and acceptor atoms, and the chemical nature of these atoms. This function has been formulated in order to reproduce experimental observations of hydrogen-bond geometries. The reorientation of hydrogen atoms and lone-pair orbitals on the formation of hydrogen-bonds is calculated analytically. The experimentally observed water structures of crystals of four biological molecules have been used as model systems for testing the GRID method. It has been shown that the location of well-ordered waters can be predicted accurately. The ability of the GRID method to assist in the assignment of water sites during crystallographic refinement has been demonstrated. It has also been shown that waters in the active site of an enzyme may be both stabilized and displaced by a bound substrate. Ligands have been designed to block the highly conserved host cell receptor site of the influenza virus haemagglutinin in order to prevent the attachment of the virus to the host cells. The protein was mapped energetically by program GRID and specific ligand binding sites were identified. Ligands, which exploited these binding sites, were then designed using computer graphics and energy minimization techniques. Some of the designed ligands were peptides and these were synthesised and assayed. Preliminary results indicate that they may possess anti-influenza activity.
APA, Harvard, Vancouver, ISO, and other styles
2

Vestergaard, Henrik Tang. "Diversity in competitive ligand-receptor interactions : electrophysiological studies of ligand-receptor interactions at native and recombinant GABAA receptors /." Cph. : Department of Pharmacology, The Danish University of Pharmaceutical Sciences, 2003. http://www.dfh.dk/phd/defences/henriktangvestergaard.htm.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Davies, Thomas Glanmor. "Protein-ligand interactions for the OppA system." Thesis, University of York, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311012.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

McFail-Isom, Lori. "Effects of ligand binding, coordinate error and ion binding on nucleic acid structure and conformation." Diss., Georgia Institute of Technology, 1998. http://hdl.handle.net/1853/30735.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Schechner-Resom, Martina Gabriele. "Ligand binding and molecular flexibility : Studies on DNA gyrase B." Université Louis Pasteur (Strasbourg) (1971-2008), 2005. http://www.theses.fr/2005STR1A001.

Full text
Abstract:
L’ADN gyrase est une enzyme vitale pour la bactérie grâce à sa capacité de manipuler les molécules d’ADN dans la cellule vivante. Cette capacité fait de l’ADN gyrase une cible idéale pour des composés anti-infectieux. Dans ce travail, l’ADN gyrase a été étudié par des méthodes de modélisatoin moléculaire. Une approche de conception de ligands basée sur la structure a été entreprise sur le sous-domaine N-terminal de 24 kDa de l’ADN gyrase B (domaine GHKL). La flexibilité de deux boucles du site actif du domaine GHKL a été étudiée par des simulations de dynamiques moléculaires en présence de différents ligands. Dans une dernière partie, une analyse des modes normaux du dimère du domaine N-terminal de 43 kDa a été entreprise
DNA gyrase is a vital bacterial enzyme necessary for the handling of the large DNA molecules in the living cell. Therefore DNA gyrase is an ideal target enzyme for anti-infectious compounds. In this work DNA gyrase has been studied by molecular modelling methods. A computational structure-based ligand design approach has been carried out on the N-terminal 24 kDa subdomain of DNA gyrase B (GHKL domain). To further examine the flexibility of two active site loops, molecular dynamics simulations have been carried out on the GHKL domain in different ligand binding conditions. In a final part, normal mode analysis has been carried out on the dimer of the 43 kDa domain of DNA gyrase B
APA, Harvard, Vancouver, ISO, and other styles
6

Shimokhina, Natalia. "Dissecting contributions to binding thermodynamics in ligand-protein interactions." Thesis, University of Leeds, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.445371.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Lampinen, Milla. "AMPA receptor ligand-binding domain : site-directed mutagenesis study of ligand-receptor interactions." Helsinki : University of Helsinki, 2003. http://ethesis.helsinki.fi/julkaisut/mat/bioti/vk/lampinen/.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Zhou, Min. "Understanding non-covalent interactions : cooperativity in ligand binding and enzyme catalysis." Thesis, University of Cambridge, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.615013.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Limson, Janice Leigh. "Electrochemical studies of metal-ligand interactions and of metal binding proteins." Thesis, Rhodes University, 1999. http://hdl.handle.net/10962/d1018239.

Full text
Abstract:
Electrochemical methods were researched for the analysis of metals, proteins and the identification of metal binding proteins. Adsorptive cathodic stripping voltamrnetry for metal analysis combines the inherent sensitivity of electrochemical techniques with the specificity of ligands for the nonfaradaic preconcentration of analytes at the electrode. The utility of catechol, resorcinol, 4-methylcatechol and 4-t-butylcatechol as ligands was explored for the sensitive analysis of copper, bismuth, cadmium and lead on a mercury film glassy carbon electrode. Metal complexes of lead, copper and bismuth with resorcinol showed the largest increase in current with increase in metal concentration, whereas complexes of these metals with 4-t-butylcatechol showed the lowest current response. Cadmium showed the highest current responses with 4-methylcatechol. The four metals could be determined simultaneously in the presence of resorcinol, although considerable interference was observed between bismuth and copper. The electroanalysis of cysteine and cysteine containing proteins at carbon electrodes are impaired by slow electron transfer rates at carbon electrodes, exhibiting high overpotentials, greater than 1 V vs Ag! Agel. Metallophthalocyanines have been shown to promote the electrocatalysis of cysteine at lowered potentials. Chemical modification of electrodes with appropriate modifiers is a means of incorporating specificity into electroanalysis, with applications in electrocatalysis. A glassy carbon electrode was modified by electrodeposition of cobalt (II) tetrasulphophthalocyanine [Co(II)TSPct to produce a chemically modified glassy carbon electrode (CMGCE). The CoTSPc-CMGCE catalysed the oxidation of cysteine in the pH range 1 to 10. The significance of this electrode is an application for analysis of proteins at biological pH's. A biscyanoruthenium(II) phthalocyanine CMGCE catalysed the oxidation of cysteine at 0.43 V vs Ag/AgCl a significant lowering in the overpotential for the oxidation of cysteine. Metallothionein, a metal binding protein, is believed to be involved in metal homeostasis and detoxification in the peripheral organs of living systems. A method for the quantitative determination of this protein utilising its high cysteine content was presented. At pH 8.4 Tris-HCl buffer, and using a CoTSPc-CMGCE modified by electrodeposition of the modifier, the anodic peaks for the oxidation of metallothionein was observed at 0. 90 V vs Ag/ AgCI. Ferredoxin is a simple iron-sulphur protein. One tenth of its residues are cysteine. Ferredoxin is involved in simple electron transfer processes during photosynthesis and respiration. Electrochemical studies of spinach ferredoxin were conducted at a CoTSPc-CMGCE. Anodic currents for the oxidation of the cysteine fragment of ferredoxin was observed at 0.85 V vs Ag/AgCl in HEPES buffer at pH 7.4, representing a new method for analysis of this protein. Voltammetric studies of its ferric/ferrous transition have shown quasi-reversible waves atE~ -0.62 V vs Ag/AgCl only in the presence of promoters. At a CoTSPc-CMGCE, a cathodic wave attributed to the reduction of Fe(III)/Fe(II) was observed at Epc -0.34 V vs Ag/AgCl. This represents an alternative method for voltammetric studies of the ferric/ferrous transition at significantly lowered potentials. Melatonin, a pineal gland hormone functions m setting and entraining circadian rhythms and in neuroprotection as a free radical scavenger and general antioxidant. Using adsorptive cathodic stripping voltammetry, the binding affinities of melatonin, serotonin and tryptophan for metals, were measured. The results showed that the following metal complexes were formed: aluminium with melatonin, serotonin and tryptophan; cadmium with melatonin and tryptophan; copper with melatonin and serotonin; iron (III) with melatonin and serotonin; lead with melatonin, tryptophan and serotonin, zinc with melatonin and tryptophan and iron (II) with tryptophan. The studies suggest a further role for melatonin in the reduction of free radical generation and in metal detoxification and may explain the accumulation of aluminium in Alzheimer's disease.
APA, Harvard, Vancouver, ISO, and other styles
10

Greguric, Antun, University of Western Sydney, of Science Technology and Environment College, and of Science Food and Horticulture School. "The DNA binding interactions of Ru(II) polypyridyl complexes." THESIS_CSTE_SFH_Greguric_A.xml, 2002. http://handle.uws.edu.au:8081/1959.7/620.

Full text
Abstract:
This thesis reports on the synthesis, characterisation, enantiomeric resolution, 1H NMR structural study and physical evaluation of a series of certain bidentate ligand metal complexes, where ‘L-L’ denotes the ancillary bidentate ligand and ‘intercalator’ indicates the intercalating bidentate ligand. The L-L series varies in size and shape. Results of many tests and projects conducted are explained in detail.
Master of Science (Hons)
APA, Harvard, Vancouver, ISO, and other styles
More sources

Books on the topic "Ligand binding interactions"

1

Protein-ligand interactions: Methods and applications. 2nd ed. New York: Humana Press, 2013.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
2

NATO ASI/FEBS Course on DNA-Ligand Interactions: From Drugs to Proteins (1986 Abbey of Fontevraud). DNA-ligand interactions: From drugs to proteins. New York: Plenum Press, 1987.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
3

1942-, Berthon Guy, ed. Handbook of metal-ligand interactions in biological fluids. New York: Marcel Dekker, 1995.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
4

Hans-Joachim, Böhm, and Schneider Gisbert 1965-, eds. Protein-ligand interactions from molecular recognition to drug design. Weinheim: Wiley-VCH, 2003.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
5

Ligand-macromolecular interactions in drug discovery: Methods and protocols. New York: Springer, 2009.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
6

Nicolae, Voiculetz, Motoc Ioan 1950-, and Simon Zeno, eds. Specific interactions and biological recognition processes. Boca Raton: CRC Press, 1993.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
7

Per, Lundahl, Lundqvist Andreas, and Greijer Eva, eds. Quantitative analysis of biospecific interactions. Australia: Harwood Academic Publishers, 1998.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
8

1942-, Berthon Guy, ed. Handbook of metal-ligand interactions in biological fluids. New York: Marcel Dekker, 1995.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
9

Nualláin, Brian Ó. An investigation of ligand interactions with apoflavodoxin from Desulfovibrio vulgaris and the cell adhesion molecule LFA-3. Dublin: University College Dublin, 1998.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
10

Symposium on Host-Guest Molecular Interactions: from Chemistry to Biology (1990 : Ciba Foundation), ed. Host-guest molecular interactions: From chemistry to biology. Chichester: Wiley, 1991.

Find full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Book chapters on the topic "Ligand binding interactions"

1

Bonomo, R. P., D. Grasso, G. Grasso, V. Guantieri, G. Impellizzeri, C. Rosa, D. Milardi, G. Pappalardo, G. Tabbì, and E. Rizzarelli. "Metal Binding to Prion Protein." In Metal-Ligand Interactions, 21–39. Dordrecht: Springer Netherlands, 2003. http://dx.doi.org/10.1007/978-94-010-0191-5_2.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Lambert, Bernard, and Jean-Bernard Le Pecq. "Pharmacology of DNA Binding Drugs." In DNA—Ligand Interactions, 141–57. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-5383-6_9.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Holdgate, Geoffrey A., and Paul E. Hemsley. "Ligand Discovery: High-Throughput Binding: Fluorescence ()." In Protein-Ligand Interactions, 231–46. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1197-5_10.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Sharp, Kim A. "Statistical Thermodynamics of Binding and Molecular Recognition Models." In Protein-Ligand Interactions, 1–22. Weinheim, Germany: Wiley-VCH Verlag GmbH & Co. KGaA, 2012. http://dx.doi.org/10.1002/9783527645947.ch1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Shaw, Joseph, and Christopher Stubbs. "Indirect Detection of Ligand Binding by Thermal Melt Analysis." In Protein-Ligand Interactions, 201–15. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1197-5_8.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Karlsson, Elin, and Per Jemth. "Kinetic Methods of Deducing Binding Mechanisms Involving Intrinsically Disordered Proteins." In Protein-Ligand Interactions, 105–33. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1197-5_4.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Goncalvès, V., and C. Mijoule. "Site and Size Effects on the Binding Energy of CO on Palladium Clusters." In Metal-Ligand Interactions, 267–88. Dordrecht: Springer Netherlands, 1996. http://dx.doi.org/10.1007/978-94-009-0155-1_10.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Schenckbecher, Emma, Guillaume Bec, Taiichi Sakamoto, Benoit Meyer, and Eric Ennifar. "Biophysical Studies of the Binding of Viral RNA with the 80S Using switchSENSE." In Protein-Ligand Interactions, 341–50. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1197-5_15.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Shriver, John W., and Stephen P. Edmondson. "Ligand-Binding Interactions and Stability." In Methods in Molecular Biology, 135–64. Totowa, NJ: Humana Press, 2008. http://dx.doi.org/10.1007/978-1-59745-367-7_6.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Steitz, T. A., L. Beese, B. Engelman, P. Freemont, J. Friedman, M. Sanderson, S. Schultz, G. Shields, and J. Warwicker. "Structural Studies of Three DNA Binding Proteins: Catabolite Gene Activator Protein, Resolvase, and the Klenow Fragment of DNA Polymerase I." In DNA—Ligand Interactions, 185–89. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4684-5383-6_13.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "Ligand binding interactions"

1

Zhang, Linda Yu, Emilio Gallicchio, and Ronald M. Levy. "Implicit solvent models for protein-ligand binding: Insights based on explicit solvent simulations." In SIMULATION AND THEORY OF ELECTROSTATIC INTERACTIONS IN SOLUTION. ASCE, 1999. http://dx.doi.org/10.1063/1.1301542.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Rossi, Barbara, Marco Giarola, Gino Mariotto, Emmanuele Ambrosi, Hugo L. Monaco, P. M. Champion, and L. D. Ziegler. "Raman Scattering Study of Ligand-Binding Interactions in SOUL Protein Single Crystals." In XXII INTERNATIONAL CONFERENCE ON RAMAN SPECTROSCOPY. AIP, 2010. http://dx.doi.org/10.1063/1.3482725.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Fedarko, Neal S., Alka Jain, Abdullah Karadag, and Larry W. Fisher. "SIBLING INTERACTIONS WITH COMPLEMENT FACTOR H AND PRO-MATRIX METALLOPROTEINASES." In 3rd International Conference on Osteopontin and SIBLING (Small Integrin-Binding Ligand, N-linked Glycoprotein) Proteins, 2002. TheScientificWorld Ltd, 2002. http://dx.doi.org/10.1100/tsw.2002.254.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Nechipurenko, Y. D., A. S. Buchelnikov, and I. A. Lavrinenko. "COOPERATIVE EFFECTS IN BINDING OF LIGANDS TO BIOPOLYMERS." In NOVEL TECHNOLOGIES IN MEDICINE, BIOLOGY, PHARMACOLOGY AND ECOLOGY. Institute of information technology, 2022. http://dx.doi.org/10.47501/978-5-6044060-2-1.257-261.

Full text
Abstract:
Models and methods of statistical thermodynamics and physical adsorption theory allow us to quantitate cooperative interactions between ligand molecules adsorbed on a macromol-ecule, in particular allosteric effects described in detail in oxygen binding to hemoglobin. We show how the Hill equation can be modified and how the Hill coefficient can be interpreted. On the other hand, the entropy of the adsorption system allows us to visualize cooperative binding processes. Cooperative interactions lead to a decrease in the entropy of the system and an increase in the information it contains.
APA, Harvard, Vancouver, ISO, and other styles
5

Brewer, Bryson M., Yandong Gao, Rebecca M. Sappington, and Deyu Li. "Microfluidic Molecular Trap: Probing Extracellular Signaling by Selectively Blocking Exchange of Specific Molecules in Cell-Cell Interactions." In ASME 2013 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2013. http://dx.doi.org/10.1115/imece2013-64489.

Full text
Abstract:
Communication among cell populations is achieved via a wide variety of soluble, extracellular signaling molecules [1]. In order to investigate the role of specific molecules in a cellular process, researchers often utilize in vitro cell culture techniques in which the molecule under question has been removed from the signaling pathway. Traditionally, this has been accomplished by eliminating the gene in the cell that is responsible for coding the targeted ligand/receptor by using modern DNA technology such as gene knockout; however, this process is expensive, time-consuming, and labor intensive. Previously, we have demonstrated a microfluidic platform that uses a semi-permeable barrier with embedded receptor-coated nanoparticles to selectively remove a specific molecule or ligand from the extracellular signaling pathway in a cell co-culture environment [2]. This initial proof-of-principle was conducted using biotinylated nanoparticles and fluorescently tagged avidin molecules, as the avidin/biotin complex is the strongest known non-covalent interaction between a protein and a ligand (Dissociation constant kd = 10−15 M). Also, the trap was only effective for short time periods (<15 min) because the high concentration of fluorescently tagged avidin molecules required for visualization quickly saturated the barrier. However, nearly all biologically relevant ligand-receptor interactions have lower binding affinities than the avidin-biotin complex, with dissociation constants that are larger by several orders of magnitude. In addition, many in vitro cell culture experiments are conducted over multiple hours or days. Thus, a practically useful molecular trap device must be able to operate in a lower binding affinity regime while also lasting for extended time periods. Here we present results in which a biotinylated-particle barrier was used to successfully block lower concentrations of fluorescently tagged avidin for multiple days, showcasing the applicability of the device for long term experiments. In addition, we introduce a modified molecular trap in which the protein A/goat IgG complex was used to demonstrate the effectiveness of the platform for lower binding affinity protein-ligand interactions. These results indicate the potential usefulness of the microfluidic molecular trap platform for probing extracellular signaling pathways.
APA, Harvard, Vancouver, ISO, and other styles
6

Solis-Calero, C., PA Morais, FF Maia Jr, VN Freire, and HF Carvalho. "Explaining SARS-CoV-2 3CL Mpro binding to peptidyl Michael acceptor and a ketone-based inhibitors using Molecular fractionation with conjugate caps method." In VIII Simpósio de Estrutura Eletrônica e Dinâmica Molecular. Universidade de Brasília, 2020. http://dx.doi.org/10.21826/viiiseedmol2020185.

Full text
Abstract:
The main protease SARS-CoV-2 3CL Mpro (3CL-Mpro) is an attractive target for developing antiviral inhibitors due to its essential role in processing the polyproteins translated from viral coronavirus RNA. In this work, it was obtained non-covalent complexes of this protease with two distinct ligands, a peptidyl Michael acceptor (N3) and a ketone-based compound (V2M). The complexes were modeled from processed crystallographic data (PDB id: 6LU7 and 6XHM respectively) using combined quantum mechanics/molecular mechanics (QM/MM) calculations. The QM region was treated at the PBE-def2-SV(P) level, while the Amber-ff19SB force field was used to describe the MM region. The obtained models were used to perform calculations for describing the protease/ligand binding, based in the framework of the Density Functional Theory (DFT) and within the Molecular Fractionation with Conjugated Caps (MFCC) scheme. Our results have shown values for the total interaction energies of -111.84 and -111.64 kcal mol-1 having as ligands a N3 and V2M, respectively. Most importantly, it was possible to assess the relative individual amino acid energy contribution for the binding of both ligands considering residues around them up to 10 Å of radial distance. Residues Gln189, Met165, Glu166, His164, and Asn142 were identified as main interacting amino acid residues for both complexes, being their negative interaction energy contributions higher than -5.0 kcal mol-1. In the case of 3CL-Mpro/ V2M complex, we should add His41, Ser144, and Cys145 as main contributing residues. Our data also have shown that interactions of type π-amide, π-alkyl and alkyl-alkyl and carbon hydrogen bonds should be also considered in order to explain the binding of 3CL-Mpro with the selected inhibitors. Our results also determined that the carbonyl-L-leucinamide scaffold of both inhibitors is its main determinant of binding with a contribution to the energy of interaction of 54.51 and 50.69 kcal mol-1 for N3 and V2M, respectively.
APA, Harvard, Vancouver, ISO, and other styles
7

Matsushita, Y., T. Murakawa, K. Shimamura, M. Oishi, T. Ohyama, and N. Kurita. "Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation." In THE IRAGO CONFERENCE 2014. AIP Publishing LLC, 2015. http://dx.doi.org/10.1063/1.4913556.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Milenković, Dejan A., Marko N. Živanović, Milan S. Dekić, Marijana Stanojević Pirković, and Jelena R. Đorović Jovanović. "CYTOTOXIC ACTIVITY AND MOLECULAR DOCKING STUDY OF 4- SUBSTITUTED FLAVYLIUM SALT." In 1st INTERNATIONAL Conference on Chemo and BioInformatics. Institute for Information Technologies, University of Kragujevac,, 2021. http://dx.doi.org/10.46793/iccbi21.466m.

Full text
Abstract:
In the present manuscript, the cytotoxic activity of flavylium cation substituted at 4- position with phenyl (FC-4Ph) was tested to two cells lines (human colorectal carcinoma, HCT-116, and human fibroblast lung, MRC-5). In vitro cytotoxicity experiments were performed to elucidate the possible anticancer activity of tested substance. Investigated compound did not show cytotoxic effect on HCT-116 after 24 h, while after 72 h exerted significant effect. A significant selectivity towards colorectal carcinoma cells was observed. On the other hand, this compound did not show any effect on MRC-5 cell line. The molecular interactions between receptor tyrosine kinase (RTK) and title compound was examined. The crystal structure of investigated receptor RTK was downloaded from Protein Data Bank. The native bound ligand ((E)-[4-(3,5-difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3- methoxyphenyl)methanol was extracted from receptor and binding pocket analysis was performed. Re-docking was carried out with the FC-4Ph in order to generate the same docking pose as found in co-crystallized form of receptor. The obtained results of revealed that investigated compound binds at the same binding pockets to RTK, as well as native bound ligand, by weak non-covalent interactions. The most prominent interactions are hydrogen bonds, π-alkyl, and π-π interactions. The preliminary results suggest that investigated compound showed good binding affinity against RTK, as evident from the free binding energy (ΔGbind in kJ/mol).
APA, Harvard, Vancouver, ISO, and other styles
9

Dimić, Dušan, Dejan Milenković, Edina Avdović, Goran Kaluđerović, and Jasmina Dimitrić Marković. "MOLECULAR DOCKING AND MOLECULAR DYNAMICS STUDIES OF THE INTERACTION BETWEEN COUMARIN-NEUROTRANSMITTER DERIVATIVES AND CARBONIC ANHYDRASE IX." In 1st INTERNATIONAL Conference on Chemo and BioInformatics. Institute for Information Technologies, University of Kragujevac,, 2021. http://dx.doi.org/10.46793/iccbi21.056d.

Full text
Abstract:
Novel biologically active compounds can be obtained by the structural modification of coumarins. In this contribution, five new derivatives of 4-hydroxycoumarin with tyramine, octopamine, norepinephrine, 3-methoxytyramine, and dopamine were obtained. Their structures were optimized based on the previously obtained crystal structure of the 4-hydroxycoumarin-dopamine derivative. The special emphasis was put on the effect of various substituents on the structure of obtained compounds and intramolecular interactions governing the stability. To investigate their possible antitumor activity, molecular docking and molecular dynamics simulations were performed with Carbonic anhydrase, a prognostic factor in several cancers, and compared to the native ligand, 5-acetamido-1,3,4-thiadiazole- 2-sulfonamide. The results have shown that all of the coumarin-neurotransmitter derivatives bind to the active pocket of protein with the binding energies higher than for the native ligand. The main contributions to the binding energies were discussed. The Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Radius of gyration (Rg), as results of MD simulations, were used to predict the activity of compounds towards chosen protein. The highest MD binding energies were obtained for the derivatives with dopamine and 3-methoxytyramine, with the van der Waals interaction and hydrogen bonds being the most important contributors.
APA, Harvard, Vancouver, ISO, and other styles
10

Bao, Gang, and Shannon Stott. "Langevin Dynamics of Hinge-Motion in Proteins." In ASME 2000 International Mechanical Engineering Congress and Exposition. American Society of Mechanical Engineers, 2000. http://dx.doi.org/10.1115/imece2000-2634.

Full text
Abstract:
Abstract Many proteins function in mechanically stressful environments. For example, shear flow in blood vessel may exert a force as high as hundreds of piconewtons on an individual selectin-ligand bond. With such a mechanical force, the receptor (selectin) may deform, thereby altering the conformational match between the receptor and the ligand. Although van der Waals forces, electrostatic and hydrophobic interactions are all important, it is often the 3D geometry local to the binding pocket that dictates the characteristics of the bond between the receptor and the ligand. Good conformational matches lead to strong and long-lasting bonds, whereas poor conformational matches do the converse. it is conceivable that conformational changes in proteins in response to various forces serve as a mechanism for transducing mechanical signals into biochemical responses.
APA, Harvard, Vancouver, ISO, and other styles

Reports on the topic "Ligand binding interactions"

1

Fernando, P. U. Ashvin Iresh, Gilbert Kosgei, Matthew Glasscott, Garrett George, Erik Alberts, and Lee Moores. Boronic acid functionalized ferrocene derivatives towards fluoride sensing. Engineer Research and Development Center (U.S.), July 2022. http://dx.doi.org/10.21079/11681/44762.

Full text
Abstract:
In this technical report (TR), a robust, readily synthesized molecule with a ferrocene core appended with one or two boronic acid moieties was designed, synthesized, and used toward F- (free fluoride) detection. Through Lewis acid-base interactions, the boronic acid derivatives are capable of binding with F- in an aqueous solution via ligand exchange reaction and is specific to fluoride ion. Fluoride binding to ferrocene causes significant changes in fluorescence or electrochemical responses that can be monitored with field-portable instrumentation at concentrations below the WHO recommended limit. The F- binding interaction was further monitored via proton nuclear magnetic resonance spectroscopy (1H-NMR). In addition, fluorescent spectroscopy of the boronic acid moiety and electrochemical monitoring of the ferrocene moiety will allow detection and estimation of F- concentration precisely in a solution matrix. The current work shows lower detection limit (LOD) of ~15 μM (285 μg/L) which is below the WHO standards. Preliminary computational calculations showed the boronic acid moieties attached to the ferrocene core interacted with the fluoride ion. Also, the ionization diagrams indicate the amides and the boronic acid groups can be ionized forming strong ionic interactions with fluoride ions in addition to hydrogen bonding interactions.
APA, Harvard, Vancouver, ISO, and other styles
2

Rafaeli, Ada, Russell Jurenka, and Chris Sander. Molecular characterisation of PBAN-receptors: a basis for the development and screening of antagonists against Pheromone biosynthesis in moth pest species. United States Department of Agriculture, January 2008. http://dx.doi.org/10.32747/2008.7695862.bard.

Full text
Abstract:
The original objectives of the approved proposal included: (a) The determination of species- and tissue-specificity of the PBAN-R; (b) the elucidation of the role of juvenile hormone in gene regulation of the PBAN-R; (c) the identificationof the ligand binding domains in the PBAN-R and (d) the development of efficient screening assays in order to screen potential antagonists that will block the PBAN-R. Background to the topic: Moths constitute one of the major groups of pest insects in agriculture and their reproductive behavior is dependent on chemical communication. Sex-pheromone blends are utilised by a variety of moth species to attract conspecific mates. In most of the moth species sex-pheromone biosynthesis is under circadian control by the neurohormone, PBAN (pheromone-biosynthesis-activating neuropeptide). In order to devise ideal strategies for mating disruption/prevention, we proposed to study the interactions between PBAN and its membrane-bound receptor in order to devise potential antagonists. Major conclusions: Within the framework of the planned objectives we have confirmed the similarities between the two Helicoverpa species: armigera and zea. Receptor sequences of the two Helicoverpa spp. are 98% identical with most changes taking place in the C-terminal. Our findings indicate that PBAN or PBAN-like receptors are also present in the neural tissues and may represent a neurotransmitter-like function for PBAN-like peptides. Surprisingly the gene encoding the PBAN-receptor was also present in the male homologous tissue, but it is absent at the protein level. The presence of the receptor (at the gene- and protein-levels), and the subsequent pheromonotropic activity are age-dependent and up-regulated by Juvenile Hormone in pharate females but down-regulated by Juvenile Hormone in adult females. Lower levels of pheromonotropic activity were observed when challenged with pyrokinin-like peptides than with HezPBAN as ligand. A model of the 3D structure of the receptor was created using the X-ray structure of rhodopsin as a template after sequence alignment of the HezPBAN-R with several other GPCRs and computer simulated docking with the model predicted putative binding sites. Using in silico mutagenesis the predicted docking model was validated with experimental data obtained from expressed chimera receptors in Sf9 cells created by exchanging between the three extracellular loops of the HezPBAN-R and the Drosophila Pyrokinin-R (CG9918). The chimera receptors also indicated that the 3ʳᵈ extracellular loop is important for recognition of PBAN or Diapause hormone ligands. Implications: The project has successfully completed all the objectives and we are now in a position to be able to design and screen potential antagonists for pheromone production. The successful docking simulation-experiments encourage the use of in silico experiments for initial (high-throughput) screening of potential antagonists. However, the differential responses between the expressed receptor (Sf9 cells) and the endogenous receptor (pheromone glands) emphasize the importance of assaying lead compounds using several alternative bioassays (at the cellular, tissue and organism levels). The surprising discovery of the presence of the gene encoding the PBAN-R in the male homologous tissue, but its absence at the protein level, launches opportunities for studying molecular regulation pathways and the evolution of these GPCRs. Overall this research will advance research towards the goal of finding antagonists for this important class of receptors that might encompass a variety of essential insect functions.
APA, Harvard, Vancouver, ISO, and other styles
3

Fagan, Patricia A. NMR studies of DNA oligomers and their interactions with minor groove binding ligands. Office of Scientific and Technical Information (OSTI), May 1996. http://dx.doi.org/10.2172/373863.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Altstein, Miriam, and Ronald J. Nachman. Rational Design of Insect Control Agent Prototypes Based on Pyrokinin/PBAN Neuropeptide Antagonists. United States Department of Agriculture, August 2013. http://dx.doi.org/10.32747/2013.7593398.bard.

Full text
Abstract:
The general objective of this study was to develop rationally designed mimetic antagonists (and agonists) of the PK/PBAN Np class with enhanced bio-stability and bioavailability as prototypes for effective and environmentally friendly pest insect management agents. The PK/PBAN family is a multifunctional group of Nps that mediates key functions in insects (sex pheromone biosynthesis, cuticular melanization, myotropic activity, diapause and pupal development) and is, therefore, of high scientific and applied interest. The objectives of the current study were: (i) to identify an antagonist biophores (ii) to develop an arsenal of amphiphilic topically active PK/PBAN antagonists with an array of different time-release profiles based on the previously developed prototype analog; (iii) to develop rationally designed non-peptide SMLs based on the antagonist biophore determined in (i) and evaluate them in cloned receptor microplate binding assays and by pheromonotropic, melanotropic and pupariation in vivo assays. (iv) to clone PK/PBAN receptors (PK/PBAN-Rs) for further understanding of receptor-ligand interactions; (v) to develop microplate binding assays for screening the above SMLs. In the course of the granting period A series of amphiphilic PK/PBAN analogs based on a linear lead antagonist from the previous BARD grant was synthesized that incorporated a diverse array of hydrophobic groups (HR-Suc-A[dF]PRLa). Others were synthesized via the attachment of polyethylene glycol (PEG) polymers. A hydrophobic, biostablePK/PBAN/DH analog DH-2Abf-K prevented the onset of the protective state of diapause in H. zea pupae [EC50=7 pmol/larva] following injection into the preceding larval stage. It effectively induces the crop pest to commit a form of ‘ecological suicide’. Evaluation of a set of amphiphilic PK analogs with a diverse array of hydrophobic groups of the formula HR-Suc-FTPRLa led to the identification of analog T-63 (HR=Decyl) that increased the extent of diapause termination by a factor of 70% when applied topically to newly emerged pupae. Another biostablePK analog PK-Oic-1 featured anti-feedant and aphicidal properties that matched the potency of some commercial aphicides. Native PK showed no significant activity. The aphicidal effects were blocked by a new PEGylated PK antagonist analog PK-dF-PEG4, suggesting that the activity is mediated by a PK/PBAN receptor and therefore indicative of a novel and selective mode-of-action. Using a novel transPro mimetic motif (dihydroimidazole; ‘Jones’) developed in previous BARD-sponsored work, the first antagonist for the diapause hormone (DH), DH-Jo, was developed and shown to block over 50% of H. zea pupal diapause termination activity of native DH. This novel antagonist development strategy may be applicable to other invertebrate and vertebrate hormones that feature a transPro in the active core. The research identifies a critical component of the antagonist biophore for this PK/PBAN receptor subtype, i.e. a trans-oriented Pro. Additional work led to the molecular cloning and functional characterization of the DH receptor from H. zea, allowing for the discovery of three other DH antagonist analogs: Drosophila ETH, a β-AA analog, and a dF analog. The receptor experiments identified an agonist (DH-2Abf-dA) with a maximal response greater than native DH. ‘Deconvolution’ of a rationally-designed nonpeptide heterocyclic combinatorial library with a cyclic bis-guanidino (BG) scaffold led to discovery of several members that elicited activity in a pupariation acceleration assay, and one that also showed activity in an H. zea diapause termination assay, eliciting a maximal response of 90%. Molecular cloning and functional characterization of a CAP2b antidiuretic receptor from the kissing bug (R. prolixus) as well as the first CAP2b and PK receptors from a tick was also achieved. Notably, the PK/PBAN-like receptor from the cattle fever tick is unique among known PK/PBAN and CAP2b receptors in that it can interact with both ligand types, providing further evidence for an evolutionary relationship between these two NP families. In the course of the granting period we also managed to clone the PK/PBAN-R of H. peltigera, to express it and the S. littoralis-R Sf-9 cells and to evaluate their interaction with a variety of PK/PBAN ligands. In addition, three functional microplate assays in a HTS format have been developed: a cell-membrane competitive ligand binding assay; a Ca flux assay and a whole cell cAMP ELISA. The Ca flux assay has been used for receptor characterization due to its extremely high sensitivity. Computer homology studies were carried out to predict both receptor’s SAR and based on this analysis 8 mutants have been generated. The bioavailability of small linear antagonistic peptides has been evaluated and was found to be highly effective as sex pheromone biosynthesis inhibitors. The activity of 11 new amphiphilic analogs has also been evaluated. Unfortunately, due to a problem with the Heliothis moth colony we were unable to select those with pheromonotropic antagonistic activity and further check their bioavailability. Six peptides exhibited some melanotropic antagonistic activity but due to the low inhibitory effect the peptides were not further tested for bioavailability in S. littoralis larvae. Despite the fact that no new antagonistic peptides were discovered in the course of this granting period the results contribute to a better understanding of the interaction of the PK/PBAN family of Nps with their receptors, provided several HT assays for screening of libraries of various origin for presence of PK/PBAN-Ragonists and antagonists and provided important practical information for the further design of new, peptide-based insecticide prototypes aimed at the disruption of key neuroendocrine physiological functions in pest insects.
APA, Harvard, Vancouver, ISO, and other styles
5

Kubas, G. J., J. Eckert, and X. L. Luo. Binding of hydrocarbons and other extremely weak ligands to transition metal complexes that coordinate hydrogen: Investigation of cis-interactions and delocalized bonding involving sigma bonds. Office of Scientific and Technical Information (OSTI), July 1997. http://dx.doi.org/10.2172/505275.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Gordon, Dalia, Ke Dong, and Michael Gurevitz. Unexpected Specificity of a Sea Anemone Small Toxin for Insect Na-channels and its Synergic Effects with Various Insecticidal Ligands: A New Model to Mimic. United States Department of Agriculture, November 2010. http://dx.doi.org/10.32747/2010.7697114.bard.

Full text
Abstract:
Motivated by the high risks to the environment and human health imposed by the current overuse of chemical insecticides we offer an alternative approach for the design of highly active insect-selective compounds that will be based on the ability of natural toxins to differentiate between insect and mammalian targets. We wish to unravel the interacting surfaces of insect selective toxins with their receptor sites on voltage-gated sodium channels. In this proposal we put forward two recent observations that may expedite the development of a new generation of insect killers that mimic the highly selective insecticidal toxins: (i) A small (27aa) highly insecticidal sea anemone toxin, Av3, whose toxicity to mammals is negligible; (ii) The prominent positive cooperativity between distinct channel ligands, such as the strong enhancement of pyrethroids effects by anti-insect selective scorpion depressant toxins. We possess a repertoire of insecticidal toxins and sodium channel subtypes all available in recombinant form for mutagenesis followed by analysis of various pharmacological, electrophysiological, and structural methods. Our recent success to express Av3 provides for the first time a selective toxin for receptor site-3 on insect sodium channels. In parallel, our recent success to determine the structures and bioactive surfaces of insecticidal site-3 and site-4 toxins establishes a suitable system for elucidation of toxin-receptor interacting faces. This is corroborated by our recent identification of channel residues involved with these two receptor sites. Our specific aims in this proposal are to (i) Determine the bioactive surface of Av3 toward insect Na-channels; (ii) Identify channel residues involved in binding or activity of the insecticidal toxins Av3 and LqhaIT, which differ substantially in their potency on mammals; (iii) Illuminate channel residues involved in recognition by the anti-insect depressant toxins; (iv) Determine the face of interaction of both site-3 (Av3) and site-4 (LqhIT2) toxins with insect sodium channels using thermodynamic mutant cycle analysis; and, (v) Examine whether Av3, LqhIT2, pyrethroids, and indoxacarb (belongs to a new generation of insecticides), enhance allosterically the action of one another on the fruit fly and cockroach paraNa-channels and on their kdr and super-kdr mutants. This research establishes the grounds for rational design of novel anti-insect peptidomimetics with minimal impact on human health, and offers a new approach in insect pest control, whereby a combination of allosterically interacting compounds increases insecticidal action and reduces risks of resistance buildup.
APA, Harvard, Vancouver, ISO, and other styles
7

Yermiyahu, Uri, Thomas Kinraide, and Uri Mingelgrin. Role of Binding to the Root Surface and Electrostatic Attraction in the Uptake of Heavy Metal by Plants. United States Department of Agriculture, 2000. http://dx.doi.org/10.32747/2000.7586482.bard.

Full text
Abstract:
The principal accomplishment of the research supported by BARD was progress toward a comprehensive view of cell-surface electrical effects (both in cell walls [CWs] and at plasma membrane [PM] surfaces) upon ion uptake, intoxication, and amelioration. The research confirmed that electrostatic models (e.g., Gouy-Chapman-Stern [G-C-S]), with parameter values contributed by us, successfully predict ion behavior at cell surfaces. Specific research objectives 1. To characterize the sorption of selected heavy metals (Cu, Zn, Pb, Cd) to the root PM in the presence of other cations and organic ligands (citric and humic acids). 2. To compute the parameters of a G-C-S model for heavy-metal sorption to the root PM. 3. To characterize the accumulation of selected heavy metals in various plant parts. 4. To determine whether model-computed ion binding or ion activities at root PM surfaces predict heavy-metal accumulation in whole roots, root tips, or plant shoots. 5. To determine whether measured ion binding by protoplast-free roots (i.e., root CWs) predicts heavy-metal accumulation in whole roots, root tips, or plant shoots. 6. To correlate growth inhibition, and other toxic responses, with the measured and computed factors mentioned above. 7. To determine whether genotypic differences in heavy-metal accumulation and toxic responses correlate with genotypic differences in parameters of the G-C-S model. Of the original objectives, all except for objective 7 were met. Work performed to meet the other objectives, and necessitated on the basis of experimental findings, took the time that would have been required to meet objective 7. In addition, work with Pb was unsuccessful due to experimental complications and work on Cd is still in progress. On the other hand, the uptake and toxicity of the anion, selenate was characterized with respect to electrostatic effects and the influences of metal cations. In addition, the project included more theoretical work, supported by experimentation, than was originally planned. This included transmembrane ion fluxes considered in terms of PM-surface electrical potentials and the influence of CWs upon ion concentrations at PM surfaces. A important feature of the biogeochemistry of trace elements in the rhizosphere is the interaction between plant-root surfaces and the ions present in the soil solution. The ions, especially the cations, of the soil solution may be accumulated in the aqueous phases of cell surfaces external to the PMs, sometimes referred to as the "water free space" and the "Donnan free space". In addition, ions may bind to the CW components or to the PM surface with variable binding strength. Accumulation at the cell surface often leads to accumulation in other plant parts with implications for the safety and quality of foods. A G-C-S model for PMs and a Donnan-plus-binding model for CWs were used successfully to compute electrical potentials, ion binding, and ion concentration at root-cell surfaces. With these electrical potentials, corresponding values for ion activities may be computed that are at least proportional to actual values also. The computed cell-surface ion activities predict and explain ion uptake, intoxication, and amelioration of intoxication much more accurately than ion activities in the bulk-phase rooting medium.
APA, Harvard, Vancouver, ISO, and other styles
8

Gurevitz, Michael, William A. Catterall, and Dalia Gordon. face of interaction of anti-insect selective toxins with receptor site-3 on voltage-gated sodium channels as a platform for design of novel selective insecticides. United States Department of Agriculture, December 2013. http://dx.doi.org/10.32747/2013.7699857.bard.

Full text
Abstract:
Voltage-gated sodium channels (Navs) play a pivotal role in excitability and are a prime target of insecticides like pyrethroids. Yet, these insecticides are non-specific due to conservation of Navs in animals, raising risks to the environment and humans. Moreover, insecticide overuse leads to resistance buildup among insect pests, which increases misuse and risks. This sad reality demands novel, more selective, insect killers whose alternative use would avoid or reduce this pressure. As highly selective insect toxins exist in venomous animals, why not exploit this gift of nature and harness them in insect pest control? Many of these peptide toxins target Navs, and since their direct use via transformed crop plants or mediator microorganisms is problematic in public opinion, we focus on the elucidation of their receptor binding sites with the incentive of raising knowledge for design of toxin peptide mimetics. This approach is preferred nowadays by agro-industries in terms of future production expenses and public concern. However, characterization of a non-continuous epitope, that is the channel receptor binding site for such toxins, requires a suitable experimental system. We have established such a system within more than a decade and reached the stage where we employ a number of different insect-selective toxins for the identification of their receptor sites on Navs. Among these toxins we wish to focus on those that bind at receptor site-3 and inhibit Nav inactivation because: (1) We established efficient experimental systems for production and manipulation of site-3 toxins from scorpions and sea anemones. These peptides vary in size and structure but compete for site-3 on insect Navs. Moreover, these toxins exhibit synergism with pyrethroids and with other channel ligands; (2) We determined their bioactive surfaces towards insect and mammalian receptors (see list of publications); (3) We found that despite the similar mode of action on channel inactivation, the preference of the toxins for insect and mammalian channel subtypes varies greatly, which can direct us to structural features in the basis of selectivity; (4) We have identified by channel loop swapping and point mutagenesis extracellular segments of the Navinvolved with receptor site-3. On this basis and using channel scanning mutagenesis, neurotoxin binding, electrophysiological analyses, and structural data we offer: (i) To identify the residues that form receptor site-3 at insect and mammalian Navs; (ii) To identify by comparative analysis differences at site-3 that dictate selectivity toward various Navs; (iii) To exploit the known toxin structures and bioactive surfaces for modeling their docking at the insect and mammalian channel receptors. The results of this study will enable rational design of novel anti-insect peptide mimetics with minimized risks to human health and to the environment. We anticipate that the release of receptor site-3 molecular details would initiate a worldwide effort to design peptide mimetics for that site. This will establish new strategies in insect pest control using alternative insecticides and the combined use of compounds that interact allosterically leading to increased efficiency and reduced risks to humans or resistance buildup among insect pests.
APA, Harvard, Vancouver, ISO, and other styles
9

Altstein, Miriam, and Ronald Nachman. Rationally designed insect neuropeptide agonists and antagonists: application for the characterization of the pyrokinin/Pban mechanisms of action in insects. United States Department of Agriculture, October 2006. http://dx.doi.org/10.32747/2006.7587235.bard.

Full text
Abstract:
The general objective of this BARD project focused on rationally designed insect neuropeptide (NP) agonists and antagonists, their application for the characterization of the mechanisms of action of the pyrokinin/PBAN (PK-PBAN) family and the development of biostable, bioavailable versions that can provide the basis for development of novel, environmentally-friendly pest insect control agents. The specific objectives of the study, as originally proposed, were to: (i) Test stimulatory potencies of rationally designed backbone cyclic (BBC) peptides on pheromonotropic, melanotropic, myotropic and pupariation activities; (ii) Test the inhibitory potencies of the BBC compounds on the above activities evoked either by synthetic peptides (PBAN, LPK, myotropin and pheromonotropin) or by the natural endogenous mechanism; (iii) Determine the bioavailability of the most potent BBC compounds that will be found in (ii); (iv) Design, synthesize and examine novel PK/PBAN analogs with enhanced bioavailability and receptor binding; (v) Design and synthesize ‘magic bullet’ analogs and examine their ability to selectively kill cells expressing the PK/PBAN receptor. To achieve these goals the agonistic and antagonistic activities/properties of rationally designed linear and BBC neuropeptide (NP) were thoroughly studied and the information obtained was further used for the design and synthesis of improved compounds toward the design of an insecticide prototype. The study revealed important information on the structure activity relationship (SAR) of agonistic/antagonistic peptides, including definitive identification of the orientation of the Pro residue as trans for agonist activity in 4 PK/PBANbioassays (pheromonotropic, pupariation, melanotropic, & hindgut contractile) and a PK-related CAP₂b bioassay (diuretic); indications that led to the identification of a novel scaffold to develop biostbiostable, bioavailable peptidomimetic PK/PBANagonists/antagonists. The work led to the development of an arsenal of PK/PBAN antagonists with a variety of selectivity profiles; whether between different PKbioassays, or within the same bioassay between different natural elicitors. Examples include selective and non-selective BBC and novel amphiphilic PK pheromonotropic and melanotropic antagonists some of which are capable of penetrating the moth cuticle in efficacious quantities. One of the latter analog group demonstrated unprecedented versatility in its ability to antagonize a broad spectrum of pheromonotropic elicitors. A novel, transPro mimetic motif was proposed & used to develop a strong, selective PK agonist of the melanotropic bioassay in moths. The first antagonist (pure) of PK-related CAP₂b diuresis in flies was developed using a cisPro mimetic motif; an indication that while a transPro orientation is associated with receptor agonism, a cisPro orientation is linked with an antagonist interaction. A novel, biostablePK analog, incorporating β-amino acids at key peptidase-susceptible sites, exhibited in vivo pheromonotropic activity that by far exceeded that of PBAN when applied topically. Direct analysis of neural tissue by state-of-the-art MALDI-TOF/TOF mass spectrometry was used to identify specific PK/PK-related peptides native to eight arthropod pest species [house (M. domestica), stable (S. calcitrans), horn (H. irritans) & flesh (N. bullata) flies; Southern cattle fever tick (B. microplus), European tick (I. ricinus), yellow fever mosquito (A. aegypti), & Southern Green Stink Bug (N. viridula)]; including the unprecedented identification of mass-identical Leu/Ile residues and the first identification of NPs from a tick or the CNS of Hemiptera. Evidence was obtained for the selection of Neb-PK-2 as the primary pupariation factor of the flesh fly (N. bullata) among native PK/PK-related candidates. The peptidomic techniques were also used to map the location of PK/PK-related NP in the nervous system of the model fly D. melanogaster. Knowledge of specific PK sequences can aid in the future design of species specific (or non-specific) NP agonists/antagonists. In addition, the study led to the first cloning of a PK/PBAN receptor from insect larvae (S. littoralis), providing the basis for SAR analysis for the future design of 2ⁿᵈgeneration selective and/or nonselective agonists/antagonists. Development of a microplate ligand binding assay using the PK/PBAN pheromone gland receptor was also carried out. The assay will enable screening, including high throughput, of various libraries (chemical, molecular & natural product) for the discovery of receptor specific agonists/antagonists. In summary, the body of work achieves several key milestones and brings us significantly closer to the development of novel, environmentally friendly pest insect management agents based on insect PK/PBANNPs capable of disrupting critical NP-regulated functions.
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Ligand binding interactions' for particular source types:
Journal articles Dissertations / Theses Books
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography