Dissertations / Theses: 'Ligards (Biochemistry)'

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

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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.

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Kandala, Srikanth. "Diphosphine Ligand Substitution in H4Ru4(CO)12: X-ray Diffraction Structures and Reactivity Studies of the Diphosphine Substituted Cluster Products." Thesis, University of North Texas, 2006. https://digital.library.unt.edu/ark:/67531/metadc5410/.

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The tetraruthenium cluster H4Ru4(CO)12 has been studied for its reactivity with the unsaturated diphosphine ligands (Z)-Ph2PCH=CHPPh2, 4,5-bis (diphenylphosphino)-4-cyclopenten-1,3-dione, bis(diphenyphosphino)benzene and 1,8- bis(diphenyl phosphino)naphthalene under thermal, near-UV photolysis, and Me3NO-assisted activation. All three cluster activation methods promote loss of CO and furnish the anticipated substitution products that possess a chelating diphosphine ligand. Clusters 1, 2, 3 and 4 have been characterized in solution by IR and NMR spectroscopies, and these data are discussed with respect to the crystallographically determined structures for all new cluster compounds. The 31P NMR spectral data and the solid-state structures confirm the presence of a chelating diphosphine ligand in all four new clusters. Sealed NMR tubes containing clusters 1, 2, 3 and 4 were found to be exceeding stable towards near-UV light and temperatures up to ca. 100°C. The surprisingly robust behavior of the new clusters is contrasted with the related cluster Ru3(CO)10(bpcd) that undergoes fragmentation to the donor-acceptor compound Ru2(CO)6(bpcd) and the phosphido-bridged compound Ru2(CO)6 (µ-PPh2)[µ-C=C(PPh2)C(O)CH2C(O)] under mild conditions. The electrochemical properties have been investigated in the case of clusters 1 and 2 by cyclic voltammetry, and the findings are discussed with respect to the reported electrochemical data on the parent cluster H4Ru4(CO)12.

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Duraj-Thatte, Anna. "Fluorescent GFP chromophores as potential ligands for various nuclear receptors." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/44764.

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Nuclear receptors are ligand activated transcription factors, where upon binding with small molecule ligands, these proteins are involved in the regulation of gene expression. To date there are approximately 48 human nuclear receptors known, involved in multiple biological and cellular processes, ranging from differentiation to maintenance of homeostasis. Due to their critical role in transcriptional regulation, these receptors are implicated in several diseases. Currently, 13% of prescribed drugs in the market are NR ligands for diseases such as cancer, diabetes and osteoporosis. In addition to drug discovery, the mechanism of function, mobility and trafficking of these receptors is poorly understood. Gaining insight into the relationship between the function and /or dysfunction of these receptors and their mobility will aid in a better understanding of the role of these receptors. The green fluorescent protein (GFP) has revolutionized molecular biology by providing the ability to monitor protein function and structure via fluorescence. The fluorescence contribution from this biological marker is the chromophore, formed from the polypeptide backbone of three amino acid residues, buried inside 11-stranded â-barrel protein. Synthesis of GFP derivatives of is based on the structure of the arylmethyleneimidazolidinone (AMI), creating a molecule that is only weakly fluorescent. Characterizing these AMI derivatives for other proteins can provide a powerful visualization tool for analysis of protein function and structure. This development could provide a very powerful method for protein analysis in vitro and in vivo. Development of such fluorescent ligands will prove beneficial for the nuclear receptors. In this work, libraries of AMIs derviatives were synthesized by manipulating various R groups around the core structure, and tested for their ability to serve as nuclear receptor ligands with the ability to fluoresce upon binding. The fluorogens are developed for steroidal and non-steroidal receptors, two general classes of nuclear receptors. Specific AMIs were designed and developed for steroid receptor estrogen receptor á (ERá). These ligands are showed to activate the receptor with an EC50 of value 3 ìM and the 10-fold activation with AMI 1 and AMI 2 in comparison to the 21-fold activation observed with natural ERá ligand, 17â-estradiol. These novel ligands were not able to display the fluorescence upon binding the receptor. However, fluorescence localized in nucleus was observed in case of another AMI derivative, AMI 10, which does not activate the receptor. Such ligands open new avenues for developing fluorescent probes for ERá that do not involve fluorescent conjugates attached to a known ERá ligand core. AMIs were also characterized for non-steroidal receptors,specifically the pregnane x receptor (PXR) and retinoic acid receptor á (RARá). To date, fluorogens which turn fluorescence upon binding and activate the receptor have not been developed for these receptors. With respect to PXR, several AMI derivatives were discovered to bind and activate this receptor with a fold-activation better than the known agonist, rifampicin. The best characterized AMI derivative, AMI 4, activates the receptor with an EC50 of value 6.3 ìM and the 154-fold activation in comparison to the 90-fold activation and an EC50 value of 1.3 ìM seen with rifamipicin. This ligand is not only able to activate PXR but also displays fluorescence upon binding to the receptor. The fluroscence pattern was observed around the nucleus. Besides AMI 4, 16 other AMI derivatives are identified that activate PXR with different activation profiles. Thus, a novel class of PXR ligands with fluorescence ability has been developed. The AMI derivatives able to bind and activate RAR, also displayed activation profiles that were comparable to the wild-type ligand, all trans retinoic acid. These ligands activated the receptor with an EC50 value of 220 nM with AMI 109 in comparison to an EC50 value of 0.8 nM with the natural ligand for RARá. When these ligands were tested for fluorescence in yeast, the yeast were able to fluoresce only in the presence of the receptor and the AMI derivative, indicating that these agonists also have the ability to fluoresce.

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Carlsson, Jens. "Challenges in Computational Biochemistry: Solvation and Ligand Binding." Doctoral thesis, Uppsala University, Department of Cell and Molecular Biology, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8738.

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Accurate calculations of free energies for molecular association and solvation are important for the understanding of biochemical processes, and are useful in many pharmaceutical applications. In this thesis, molecular dynamics (MD) simulations are used to calculate thermodynamic properties for solvation and ligand binding.

The thermodynamic integration technique is used to calculate pK_a values for three aspartic acid residues in two different proteins. MD simulations are carried out in explicit and Generalized-Born continuum solvent. The calculated pK_a values are in qualitative agreement with experiment in both cases. A combination of MD simulations and a continuum electrostatics method is applied to examine pK_a shifts in wild-type and mutant epoxide hydrolase. The calculated pK_a values support a model that can explain some of the pH dependent properties of this enzyme.

Development of the linear interaction energy (LIE) method for calculating solvation and binding free energies is presented. A new model for estimating the electrostatic term in the LIE method is derived and is shown to reproduce experimental free energies of hydration. An LIE method based on a continuum solvent representation is also developed and it is shown to reproduce binding free energies for inhibitors of a malaria enzyme. The possibility of using a combination of docking, MD and the LIE method to predict binding affinities for large datasets of ligands is also investigated. Good agreement with experiment is found for a set of non-nucleoside inhibitors of HIV-1 reverse transcriptase.

Approaches for decomposing solvation and binding free energies into enthalpic and entropic components are also examined. Methods for calculating the translational and rotational binding entropies for a ligand are presented. The possibility to calculate ion hydration free energies and entropies for alkali metal ions by using rigorous free energy techniques is also investigated and the results agree well with experimental data.

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Mallov, Ian. "Coordination Chemistry of Diindole Ligands: Synthesis and Reactivity of a Di(indolyl)bicyclononylborate Ligand and Explorations in Main Group Diindolylmethane Chemistry." Thesis, University of Ottawa (Canada), 2010. http://hdl.handle.net/10393/28584.

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Chapter One gives a brief overview of established coordination chemistry of pyrrole and indole-based ligands, and of the ansa-metallocene chemistry of ligands featuring a heteroatom in the bridging position. Proposals for syntheses of coordination compounds of two different ansa-indolyl ligand systems are outlined. Chapter Two describes the synthesis and characterization of an anionic diindolylborate ligand and outlines attempted reactivity with transition metal and main group halides. Spectroscopic results from these reactions as well as reactions to synthesize variants of this ligand are presented. The final section details syntheses of variants of a known diindolylmethane ligand. Chapter Three presents the first well-characterized Group 13 coordination compounds of the di(3-methylindol-2-yl)-4-bromophenylmethane ligand. Hydrogen-elimination reactions producing borane and alane complexes in high yield were employed. Spectroscopic characterization is presented, as well as solid-state structural characterization of the borane. Further reactivity with trimethylaluminum is explored but results are not as definitive. Chapter Four details the first explored reactivity of the diindolylmethane ligand with metals from the s-block. Dinuclear compounds of lithium, sodium, and potassium were obtained by reaction of di(3-methylindolyl)-4-bromophenylmethane with common amides of the metals. All three compounds proved reactive with metal halides and their utility as precursors to further coordination complexes was demonstrated by reaction with calcium iodide. The potassium salt yielded a calcium complex of di(3-methylindolyl)-4-bromophenylmethane, the first known Group 2 complex of diindolylmethane. Chapter Five explores reactivity with Group 15 phosphine and stibine reagents. Phosphine halides of both di(3-methylindolyl)-4-bromophenylmethane and di(3-methylindolyl)- 4-fluorophenylmethane were synthesized and characterized spectroscopically. A solid-state structure of di-(3-methylindol-2-yl)chlorophosphine-4-bromophenylmethane was obtained. The purposes of targeting these compounds was to establish diindolylmethane as a viable supporting framework for Group 15 compounds, to examine relative Lewis basic properties of the diindolylmethane ligand system, and to determine if they were a suitable route to phosphenium cations. A diindolylmethane complex of an amidostibine was also obtained and characterized by spectroscopic and elemental analysis. Attempts toward both phosphenium and stibenium cations through halide abstraction and substituent protonation, respectively, did not yield the expected cations.

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McGregor, Lynn Marie. "Methods for the Identification of Ligand-Target Pairs from Combined Libraries of Targes and Ligands." Thesis, Harvard University, 2014. http://dissertations.umi.com/gsas.harvard:11370.

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Advances in genome and proteome research have led to a dramatic increase in the number of macromolecular targets of interest to the life sciences. A solution-phase method to simultaneously reveal all ligand-target binding pairs from a single solution containing libraries of ligands and targets could significantly increase the efficiency and effectiveness of target-oriented screening efforts. Here, we describe interaction-dependent PCR (IDPCR), a solution-phase method to identify binding partners from combined libraries of small-molecule ligands and targets in a single experiment. Binding between DNA-linked targets and DNA-linked ligands induces formation of an extendable duplex. Extension links codes identifying the ligand and target into one selectively amplifiable DNA molecule. In a model selection, IDPCR resulted in the enrichment of DNA encoding all five known protein-ligand pairs out of 67,599 possible sequences.

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Fernández, Lola. "Studies on the biochemistry and cell biology of the glycosyl-phosphatidylinositol (GPI)-anchored NKG2D-ligands." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609534.

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Burton, Nicolas Paul. "Novel ligands for affinity chromatography." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.359769.

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Proctor, Lavinia M. "Pharmacological activity of C3a and C3a receptor ligands /." [St. Lucia, Qld.], 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18423.pdf.

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Richmond, Meaghan L. "The design, synthesis, and application of new amino acid-based modular N-ethylenediamine ligands /." View online version; access limited to Brown University users, 2005. http://wwwlib.umi.com/dissertations/fullcit/3174664.

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Shinde, Patil Vivek R. "Biophysics and Biochemistry of Receptor-Ligand Mediated Adhesion to the Endothelium." Ohio University / OhioLINK, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1020445377.

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Don, Ming-jaw. "Ligand Substitution Studies in the Tetracobalt Cluster Co₄(CO)₁₀([mu]₄-PPh₂) and Synthesis and Reactivity Studies in the Fe₂Pt and FeCo₂ Mixed-metal Clusters." Thesis, University of North Texas, 1991. https://digital.library.unt.edu/ark:/67531/metadc279335/.

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The kinetics of ligand substitution for CO in Co4(CO)10(mu4-PPh2) , 1, have been investigated for the ligands P(OMe)3, P(OEt)3, PPh2H, P(0-i-Pr)3, P(n-Bu)3, PPh3, P(i-Pr)3, and PCy3 over a wide temperature range.

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Allan, Christine Elizabeth. "Synthesis and pharmacological characterisation of novel fluorescent ligands." Thesis, University of Glasgow, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272454.

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Kissel, Daniel Stephen. "Metal ion complexing properties of two dimensional sulfur ligands and their use in neurodegenerative disease." View electronic thesis (PDF), 2009. http://dl.uncw.edu/etd/2009-3/kisseld/danielkissel.pdf.

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Gan, Wei. "Synthesis and design of fluorescence ligands to act as sensor for zinc /." Electronic version (PDF), 2004. http://dl.uncw.edu/etd/2004/ganw/weigan.html.

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Zhang, Zhanping. "Neuron-ligand pathfinding studies by atomic force microscopy and other surface-sensitive methods." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 249 p, 2006. http://proquest.umi.com/pqdweb?did=1172109001&sid=2&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Muehl, Brian S. "The synthesis and study of phosphine crown ether ligands, and an investigation of how the binding of sodium or potassium ions affects the donor ability of the phosphorus center." Virtual Press, 1992. http://liblink.bsu.edu/uhtbin/catkey/834529.

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The phosphine crown ether, 16-(4'diphenylphosphinophenyl)-1,4,7,10,13-pentaoxa-16azacyclooctadecane (III), was synthesized using a reaction scheme beginning with n-phenyldiethanolamine and the dichloride of tetraethylene glycol, with an overall yield of 4%. Platinum and Palladium complexes of the ligand, of the form MC12L2, were synthesized as well. 13C NMR and picrate extraction data indicate III and IV (the crown-5 analog) both moderately bind sodium (14%, 15%) and potassium ions (17%, 28%). Compound V (a crown-5, triphenylphosphine-based ligand) will bind both sodium and potassium ions as well (18%, 6%). When IV is complexed to nickel carbonyl (Ni(CO)3), the addition of sodium and potassium ions cause the Al carbonyl stretching frequency to increase slightly (0.3 cm-1, 0.2 cm 1). For comparison, the addition of a proton causes the A1 carbonyl stretching frequency to increase 5.2 cm-1. However, the shift in the A1 carbonyl stretching frequency upon the addition of sodium or potassium ions indicates that ion binding by the crown ether is communicated to the phosphorus and finally to the carbonyl groups.Ball State UniversityMuncie, IN 47306
Department of Chemistry

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Bidon-Chanal, Badia Axel. "Estudio teórico del transporte de ligandos en proteínas y de la afinidad ligando-receptor." Doctoral thesis, Universitat de Barcelona, 2007. http://hdl.handle.net/10803/672848.

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La eficacia de un ligando en su interacción con una macromolécula biológica depende no solo de su capacidad para interaccionar de forma complementaria y específica con la constelación de grupos químicos presentes en el centro de unión, sino también de su difusión a través de la matriz proteica para alcanzar dicho centro. Aunque difusión y unión reflejan el balance de fuerzas intermoleculares establecido entre ligando y receptor, los determinantes moleculares que subyacen pueden ser diferentes. lo que plantea un reto en su descripción mediante modelización. Con el objetivo general de identificar los determinantes moleculares asociadas a difusión y unión de ligandos en dos sistemas de relevancia biológica planteamos el análisis de dos sistemas. Por un lado, Ia acetilcolinesterasa, donde nos interesó Ia identificación de los factores que determinan la afinidad entre ligando y receptor. Por otro lado, la hemoglobina truncada N de M. tuberculosis, donde nos interesó estudiar el mecanismo molecular asociado a la difusión de ligandos a través de la matriz proteica. En cuanto al enzima acetilcolinesterasa, los objetivos específicos del presente trabajo consisten en Ia identificación de los determinantes moleculares que modulan la afinidad de tres tipos de inhibidores duales: A.l) deri vados tacrina-ftalimida, A.2) derivados tacrina-indol y A.3) deri vados tacrina-donepezilo. Todos ellos tienen como motivo común el anillo de tacrina (o cloro-tacrina), cuya presencia debería permitir la unión al centro catalítico del enzima, mientras que las estructuras consideradas difieren en la unidad química destinada a interaccionar con el centro periférico. Con respecto a la hemoglobina trucada N de M. tuberculosis, los objetivos especificos que se han planteado en este trabajo son: B. l) identificar el mecanismo molecular de migración de ligandos diatómicos (O2 y NO) hacia el centro activo, prestando especial atención a las características estructurales de las dos ramas del túnel observado en la matriz proteica, y su implicación funcional en la migración de ligandos, y B.2) establecer el mecanismo de liberación del anión nitrato, cuya salida a través del túnel observado en la estructura de rayos X no puede explicarse de forma convincente teniendo presente tanto su carga neta como su tamaño, por lo cual cabe especular con la posibilidad de que exista una ruta de eliminación altemativa no observada en la estructura cristalográfica.

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Cheung, Wai Man. "Transition metal complexes with dichalcogenoimidodiphosphinate ligands /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202007%20CHEUNG.

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Conroy, S. "Design and synthesis of novel P2Y2 receptor ligands." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/51072/.

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The P2Y2 receptor (P2Y2R) has been implicated in a range of clinical conditions, including but not limited to: cystic fibrosis, dry eye syndrome and cancer. However, a lack of high quality, drug-like modulators and tool-like compounds means there is scope to develop ligands that can further probe P2Y2R function in vitro and in vivo. Assessment of the reported P2Y2R antagonists led to the conclusion that 5-((5-(2,8-dimethyl-5H-dibenzo[a,d][7]annulen-5-yl)-2-oxo-4-thioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-N-(1H-tetrazol-5-yl)furan-2-carboxamide (AR-C118925, 38) was the most drug-like P2Y2R antagonist and was chosen as a chemical starting point. Elaboration of the 2,8-dimethyl-5H-dibenzo[a,d]cyclohepten-5-yl moeity to a 7-chloro-2-methyl-4H-benzo[5,6]cyclohepta[1,2-d]thiazol-4-yl), led to the development of two potent, novel P2Y2R antagonists: MSG204 105 (pKB = 6.73 0.25, n = 3) and MSG249 119 (pKB = 7.06 0.02, n = 3), both of which exhibit improved physicochemical properties to AR-C118925 38 and provide more drug-like alternatives for future in vivo work. Structure activity relationships derived in developing these novel P2Y2R antagonists, has ultimately led to the development of multiple fluorescently-labelled P2Y2R ligands. Most notably, BODIPY 630/650 conjugate MSG260 193 (pKd = 6.99 0.04, n = 3) and BODIPY FL conjugate MSG262 195 (pKd = 6.88 0.01, n = 3), which have enabled the use of a novel P2Y2R BRET ligand-binding assay and provide a robust platform for future drug discovery programs.

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Abdulrazzaq, Ghayth. "Assessment of GPR18 pairing with putative cannabinoid ligands." Thesis, University of Nottingham, 2018. http://eprints.nottingham.ac.uk/49680/.

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GPR18 receptor is a candidate cannabinoid receptor with potential of being a novel therapeutic target due to its wide distribution in various tissues. NAGly which is a metabolite of the first isolated endocannabinoid anandamide, had been suggested by several studies as an endogenous high potency ligand of GPR18 receptor. Yet, some studies have reported the lack of activation of GPR18 by NAGly and some other putative GPR18 cannabinoid ligands. Identifying the signalling mechanism of GPR18 will advance our understanding of the complexity of the endocannabinoid system and may have important implications in determination of the molecular mechanism of action of phytocannabinoids. The rationale of this study was to characterize the pharmacology of GPR18 by investigating the effects of NAGly and other putative GPR18 cannabinoid ligands like THC, Abn-CBD, O-1918 and NARAS on the intracellular signalling mediators, extracellular signal-regulated kinases (ERK1/2) and Ca2+ ions in HEK293TR heterologously expressing GPR18 receptor as well as the cell lines that have been reported in previous studies to express GPR18 endogenously or show biological responses to NAGly namely, mouse microglial cells (BV-2), rat insulinoma β-cell line (INS-1 832/13 β-cells) and human colorectal cancer cells (Caco-2). Changes in the intracellular Ca2+ were also measured following co-expression of GPR18 in Chinese hamster ovarian cell line (CHO) heterologously expressing CB2 and exposure to the GPR18 putative ligands. SNAP-tagged human GPR18 receptor under the control of a tetracycline regulated expression system was heterologously expressed in HEK293TR cells. The effect of putative GPR18 agonists on intracellular Ca2+ mobilisation was assessed using FlexStation and single cell Ca2+ imaging techniques with different Ca2+ probes (fluo-4 and fura-2). NAGly induced ERK phosphorylation was quantified by immunoblotting. The tested panel of cannabinoid ligands did not observed to elicit a significant ligand-mediated phosphorylation of ERK1/2 or mobilisation of intracellular Ca2+ in GPR18-expressing HEK293TR cells, BV-2 cells, INS-1 832/13 β-cells, Caco-2 cells and GPR18-transfected CHO cells heterologously expressing CB2 receptors. In this study recombinant human GPR18 receptor was not activated by NAGly or other cannabinoid ligand suggested by previous studies which indicated that NAGly may be not the natural endogenous ligand of GPR18 and argue against the deorphanization of GPR18 and assignment as a candidate cannabinoid receptor. Also it can concluded that the activation of GPR18 signalling mechanism may involve prodigious pathways not examined in the current study.

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Jiang, Ning. "Kinetic analysis of Fcγ receptor and T cell receptor interacting with respective ligands." Diss., Georgia Institute of Technology, 2005. http://hdl.handle.net/1853/26716.

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Low affinity Fcg receptor III (FcgRIII, CD16) triggers a variety of cellular events upon binding to the Fc portion of IgG. A real-time flow cytometry method was developed to measure the affinity and kinetics of such low affinity receptor/ligand interactions, which was shown as an easily operated yet powerful tool. Results revealed an unusual temperature dependence of reverse rate of CD16aTM dissociating from IgG. Except for a few studies using mammalian cell CD16s, most kinetics analyses use purified aglycosylated extracellular portion of the molecules, making it impossible to assess the importance of the receptor anchor and glycosylation on ligand binding. We used a micropipette adhesion frequency assay to demonstrate that the anchor length affects the forward rate and affinity of CD16s for IgG in a species specific manner, most likely through conformational changes. Receptor glycosylation dramatically reduced ligand binding by 100 folds. T cell receptor (TCR) is arguably the most important receptor in the adaptive human immune system. Together with coreceptor CD4 or CD8, TCR can discriminate different antigen peptides complexed with major histocompatibility complex (MHC) molecule (pMHC), which differ by as few as only one amino acid, and trigger different T cell responses. When T cell signaling was suppressed, TCR had similar affinity and kinetics for agonist and antagonist pMHC whose binding to CD8 was undetectable. TCR on activated T cell had a higher affinity for pMHCs, suggesting that TCRs organize themselves differently on activated T cells than on naïve T cells. In the absence of inhibitors for signaling, TCR binds agonist pMHC with several orders of magnitude higher affinity than antagonist pMHC. In addition, engagement of TCR by pMHC signals an upregulation of CD8 binding to pMHC, which is much stronger than the TCR-pMHC binding. The transition from weak TCR binding to the strong CD8 binding takes place around 0.75 second after TCR in contact with pMHC and can be reduced by several inhibitors of tyrosine and lipid phosphorylation, membrane rafts, and actin cytoskeleton. These results provide new insights to understanding T cell discrimination.

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Gaver, Charles Richard. "The highly preorganized ligands 8-(2-Pyridyl) Quinoline, 2,2'-dipyridyl amine and 1,10-phenanthroline-2, 9-dicarboxylic acid, and their complexing properties with metal ions." View electronic thesis, 2008. http://dl.uncw.edu/etd/2008-3/gaverc/charlesgaver.pdf.

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Chauhan, Vinita. "Low density lipoprotein receptor, interaction with ligands and molecular chaperone proteins." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ66136.pdf.

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Al-yahyaee, Said Ali Suleiman. "Conjugation of cytolytic toxin to targeting ligands alters specificity and toxicity." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.339473.

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Potgieter, Kim Carey. "Rhenium complexes with multidentate benzazoles and related N,X-donor (X = N, O, S) ligands." Thesis, Nelson Mandela Metropolitan University, 2012. http://hdl.handle.net/10948/d1020773.

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The coordination behaviour of 4-aminoantipyrine (H2pap) and its Schiff base derivatives with the oxorhenium(V) and tricarbonyl rhenium(I) cores are reported. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with H2pap were studied, and the complexes cis-[ReX2(pap)(H2pap)(PPh3)](ReO4) were isolated. The ligand pap is coordinated monodentately through the doubly deprotonated amino nitrogen as an imide, and H2pap acts as a neutral bidentate chelate, with coordination through the neutral amino nitrogen and the ketonic oxygen. The reactions of trans-[ReOBr3(PPh3)2] and cis-[ReO2I(PPh3)2] with -(2-aminobenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (H2nap) and 4-(2-hydroxybenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (Hoap) are also reported. The complexes cis-[Re(nap)Br2(PPh3)]Br, [ReO(OEt)(Hnap)(PPh3)]I and [ReO(OMe)(oap)(PPh3)]I were isolated and structurally characterized. The reactions of the Schiff base derivatives 1,2-(diimino-4’-antipyrinyl)ethane (dae) and 2,6-bis(4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one)pyridine (bap) with [Re(CO)5X] (X = Br or Cl) produced fac-[Re(CO)3(dae)Cl] and fac-[Re(CO)3(bap)Br] respectively. A series of rhenium(I) tricarbonyl complexes containing bidentate derivatives of aniline was synthesized and structurally characterized. With 1,2-diaminobenzene (Hpda) the ‘2+1’ complex salt fac-[Re(CO)3(κ1-Hpda)(κ2-Hpda)]Br was isolated, but with 2-mercaptophenol (Hspo) the bridged dimer [Re2(CO)7(spo)2] was found. The neutral complex [Re(CO)3(ons)(Hno)] was isolated from the reaction of [Re(CO)5Br] with 2-[(2-methylthio)benzylideneimino]phenol (Hons; Hno = 2-aminophenol), with ons coordinated as a bidentate chelate with a free SCH3 group. In the complex [Re(CO)3(Htpn)Br] (Htpn = N-(2-(methylthio)benzylidene)benzene-1,2-diamine) the potentially tridentate ligand Htpn is coordinated via the methylthiol sulfur and imino nitrogen atoms only, with a free amino group. These rhenium(I) complexes, with the exception of [Re2(CO)7(spo)2], revealed broad emissions centred around 535 nm. The reactions of the rhenium(V) complex cis-[ReO2I(PPh3)2] with 2-aminothiophenol (H2atp), benzene-1,2-dithiol (H2tdt) and 2-hydroxybenzenethiol (H2otp) led to the formation of the rhenium(III) compounds [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 (ibsq = 2-iminothiobenzosemiquinonate, sbsq = 1,2-dithiobenzosemiquinonate, obsq = 2-hydroxothiobenzosemiquinonate) respectively. The complexes adopt a trigonal prismatic geometry around the rhenium centre with average twists angles between 3.20-26.10˚. The E1/2 values for the Re(III)/Re(IV) redox couple were found to be 0.022, 0.142 and 0.126 V for [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 respectively. The reactions of the benzoxazole ligands, 3-(benzoxazol-2-yl)pyridin-2-ol (Hbop) and 5-amino-2-(benzoxazol-2-yl)phenol (Habo) with a [ReO]3+ precursor led to the rhenium(III) complex, [ReCl2(bop)(PPh3)2], and the complex salt, [ReO(abo)I(PPh3)2]ReO4, respectively. A variety of benzothiazole and benzimidazole derivatives were reacted with [Re(CO)5Br]. In the case of bis(benzothiazol-2-ylethyl)sulfide (bts), the neutral complex fac-[Re(CO)3(bts)Br] was obtained. The dimeric complexes (μ-dbt)2[Re(CO)3]2 and (μ-mbt)2[Re(CO)3]2 were formed when 1,3-bis(benzothiazol-2-yl)thiourea (Hdbt) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) were used as ligands. The reaction of 2,2’-(oxybis(methylene))bis(benzimidazole) (bmb) with [Re(CO)5Cl] resulted in the rhenium(I) complex salt fac-[Re(CO)3(bmb)]+, with the tri-μ-chlorohexacarbonyl dirhenate [Re2(CO)6Cl3]- as the counter anion. The neutral complex fac-[Re(CO)3(btp)Cl] was isolated from the reaction of the 2,9-bis(benzothiazol-2-yl)-1,10-phenanthroline (btp) ligand and [Re(CO)5Cl]. The reactions of trans-[ReOCl3(PPh3)2] with bis(benzimidazol-2-ylethyl)sulfide (btn) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) led to the formation of the cationic compounds (μ-O)2[Re2O2(btn)2]I2 and [ReCl2(bte)(PPh3)2]Cl (bte = (benzothiazole-2-yl)-N-ethylidenemethanamine) respectively.

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27

Howerton, Shelley B. "Structural characterization of B-DNA and its interactions with cations and intercalating ligands." Diss., Georgia Institute of Technology, 2002. http://hdl.handle.net/1853/30557.

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28

Yan, Jing, and 严静. "The anticancer properties of gold (III) complexes with tridentate cyclometalated, porphyrinato and glycosylated ligands." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B4587265X.

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29

Kapp, Eugene Anthony. "Isolation, purification and effect of ligands on the nicotinic cholinergic receptor." Thesis, Rhodes University, 1989. http://hdl.handle.net/10962/d1018235.

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The nicotinic cholinergic receptor protein of the fish electric organ, Torpedo fuscomaculata, has been isolated, purified and shown to represent a true model for the nAChR from other species and higher vertebrates. It is an integral membrane protein composed of four different subunits, tightly associated with other functional, but non-specific proteins. Purification of the nicotinic cholinergic receptor by chromatofocusing demonstrates an improved method over that of affinity and ion-exchange chromatography. Gel chromatography and SDS-polyacrylamide gel electrophoresis show evidence of four subunits; a(40-44 kDa), 6(53 kDa ),'Y(63 kDa) and 6(66 kDa) despite some degradation of receptor molecules by intracellular proteases. Spectrophotometric and fluorimetric studies of receptor-ligand interactions, show the functional and chemical integrity of the receptor to remain intact after solubilisation. The effect of cholinergic ligands on purified receptor preparations indicate quenching of the intrinsic fluorescence of the receptor. Agonists, like acetylcholine, bind and cause local conformational transitions, changing the active region from a hydrophobic to a hydrophilic environment. This phenomenon is illustrated by the 10-fold increase in fluorescence when the receptor is in a desensitised state. Antagonists, such as d-Tubocurarine, block this conformational transition. In vitro rectus abdominis muscle preparations . show the nitrosamines, dimethylnitrosamine and diphenylnitrosamine, to be true agonists of the nAChR. However their low affinity and specificity for the receptor precludes them as photoaffmity labelling agents. Photoactivation of dimethylnitrosamine occurs when associated with an acidic hydrogen at the active site of the receptor, suggesting energy-transfer labelling to be more facile than photoaffmity labelling. The membrane-bound receptor, in the presence of these nitrosamines, undergoes conformational transitions regulating the opening and closing of the ion-channel. Desensitisation and receptor activation are shown to involve one and the same molecular transition.

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30

Guo, Guanlun. "Stereo-selective binding of enantiomeric ligands in PPAR[gamma] : a molecular modeling study." HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1516.

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31

Turlais, Fabrice Urbain. "Ligands for the voltage dependent DHP sensitive Ca'2'+ channels from microalgae." Thesis, University of Hertfordshire, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309717.

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32

Spencer, Sarah Jane. "Novel fenofibrate derivatives as cannabinoid receptor ligands." Thesis, University of Nottingham, 2011. http://eprints.nottingham.ac.uk/12298/.

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Fenofibrate is a PPARα agonist, used to treat dyslipidemia. Unpublished work that has been previously carried out in our group has identified that fenofibrate also displays affinity for the cannabinoid receptors, CB1 and CB2. A dual receptor ligand, with the PPARα agonist activity of fenofibrate, combined with antagonist activity at the CB1 receptor, or agonist activity at the CB2 receptor, could reduce appetite, decrease plasma triglyceride levels, increase high density lipoprotein (HDL) levels, lower low density lipoprotein (LDL) levels and reduce atherosclerosis. This could enable the multi-symptomatic treatment of obesity with the advantage of avoiding side effects associated with taking multiple medications. However, whilst fenofibrate has affinity for the cannabinoid receptors, only its active metabolite; fenofibric acid (10b) activates PPARα. This project sought to develop novel ligands for the cannabinoid receptors that retain activity at PPARα. A series of amide derivatives of fenofibrate were synthesised, and pharmacological testing revealed that the piperidinyl (48g) and morpholino (48h) derivatives had agonist activity and a higher affinity for the cannabinoid receptors than fenofibrate. However these derivatives failed to bind and activate PPARα. Although a dual PPARα / cannabinoid receptor ligand has not been found with these amide derivatives, the compounds synthesised could provide a platform for the further development of cannabinoid receptor ligands of this novel class. This was demonstrated by further modifications to compounds (48g) and (48h) which indicated that activity at the cannabinoid receptors is tuneable.

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33

Holt, Christopher James. "Design, synthesis and evaluation of fluorescent CB2 cannabinoid receptor ligands." Thesis, University of Nottingham, 2009. http://eprints.nottingham.ac.uk/10712/.

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Cannabis has been used as a medicinal and natural product for thousands of years. Whether it has been used to make rope or paper, or been used to treat pain or depression, cannabis has always had a place in human civilisation. With the isolation of the psychoactive compounds responsible for cannabis’ effects, the discovery of two human cannabinoid receptors and an expanding knowledge of the therapeutic uses of cannabis, interest in the development of novel cannabinoids grew. The CB2 cannabinoid receptor has gained particular attention, as the often unwanted central and psychoactive effects of cannabinoids has been attributed to the CB1 cannabinoid receptor. Development of CB2 receptor selective ligands offers treatment opportunities in many areas, but most especially for pain, multiple sclerosis and immunomodulation. The preparation of fluorescently labelled ligands for a variety of receptors has improved compound screening techniques, as well as allowing use as biomolecular probes for aiding our understanding of the receptor in situ. The aim of this work is to design, synthesise and evaluate novel fluorescently labelled cannabinoids, with a particular interest in CB2 selective compounds. Focusing on the CB2 receptor selective alkylindole JWH-015, targeted substitutions were made to its naphthyl ring to identify sites that might be suitable for fluorophore attachment. With a site chosen, a series of fluorescent JWH-015 analogues was synthesised and evaluated for their CB2 receptor binding affinities. Though none of the evaluated compounds showed sufficient binding affinity for them to be used as biomolecular tools, the structure activity relationships gained suggested that improved design of fluorescent JWH-015 analogues in future could lead to the first ever active fluorescent cannabinoid.

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34

Zhang, Xiaochen 1969. "The binding modes of maltose binding protein with different ligands studied by NMR /." Thesis, McGill University, 1997. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=27438.

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Maltose Binding Protein (MBP) of Escherichia Coli, a kind of periplasmic protein, can bind its ligands interacting predominantly either with their anomeric end (end-on binding) or with the middle of the maltodextrin chain (middle binding). Using NMR spectroscopy, we have studied the modes by which maltose, linear maltodextrin and some derivatives like $ beta$-cyclodextrin bind to MBP. 1D proton difference spectra and 2D HSQC proton-nitrogen correlation spectra were acquired of MBP in the presence of different ligands. Spectra with linear maltodextrins showed many common features and were distinctly different from those of MBP with $ beta$-cyclodextrin. 2D HSQC spectra suggest further that MBP- $ beta$-cyclodextrin adopts an open form conformation similar to that of ligand free MBP because of the surprisingly similarity of their spectra. Ligands such as $ beta$-cyclodextrin, can not be transported into the cyto-plasm but have high affinity for MBP, multiple $ alpha$(1-4) linkages and no reducing end. These ligands bind to MBP mainly by the middle binding mode. This suggests that this mode determines high affinity binding of ligand to MBP, but doesn't produce a physiologically active complex.

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35

Keyser, Rowena J. "Identifying ligands of the C-terminal domain of cardiac expressed connexin 40 and assessing its involvement in cardiac conduction disease." Thesis, Link to online version, 2007. http://hdl.handle.net/10019/651.

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36

Clifton, Heather A. "Computational antiviral drug design." Muncie, Ind. : Ball State University, 2009. http://cardinalscholar.bsu.edu/645.

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37

Stuart, Guy Robert. "Structural and functional characterisation of C1q receptor (an isoform of calreticulin) and its ligands." Thesis, University of Oxford, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364024.

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Allan, David Simon Joseph. "Non-classical MHC class I molecules HLA-E and HLA-G and their ligands." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365371.

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39

Farhang-Fallah, Janet Rozakis-Adcock Maria. "Cloning and characterization of PHIP, a novel protein ligand of the PH domain of IRS-1 /." *McMaster only, 2002.

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40

Stamp, Anna Louise Elizabeth. "Structural studies of protein - ligand interactions : potential biomedical implications." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670175.

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41

Malasi, Wilhelm S. "Synthesis and complexation of functionalized mixes thia-aza-macrocyclic and medium sized ligands." Akron, OH : University of Akron, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1239210466.

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Thesis (Ph. D.)--University of Akron, Dept. of Chemistry, 2009.
"May, 2009." Title from electronic dissertation title page (viewed 11/25/2009). Advisor, Michael J. Taschner; Committee members, David Modarelli, Jun Hu, Wiley J. Youngs, Amy Milsted; Department Chair, Kim C. Calvo; Dean of the College, Chand Midha; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

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42

Siddons, Chynthia Janette. "Metal ion complexing properies [i.e. properties] of amide donating ligands /." Electronic version (PDF), 2004. http://dl.uncw.edu/etd/2004/siddonsc/chynthiasiddons.pdf.

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43

Xue, Genqiang. "Homo- and heterodinuclear metallocomplexes for biomimetic hydrolysis : design, synthesis, structure and catalytic activity /." View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202004%20XUE.

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44

Agüera-González, Sonia. "Cell biology on NKG2D ligands and NK cell recognition." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609348.

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45

Smith, Aubrey L. "Facilitating multi-electron reactivity at low-coordinate cobalt complexes using redox-active ligands." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42745.

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In this study, we describe a detailed investigation of cobalt complexes containing redox-active ligands. We have prepared an electronic series of the complex in three oxidation states: [CoIII(ap)2]-, CoIII(isq)(ap), and [CoIII(CH3CN)(isq)2]+. Characterization shows that the metal center remains cobalt(III) through the redox changes and indicates that the oxidation state changes occur with gain or loss of electrons from the ligand set. While CoIII(isq)(ap) reacts with halide radicals to form a new cobalt-halide bond in a single electron reaction, [CoIII(ap)2]- appears to be prone to multi-electron reactivity in reactions with sources of "Cl+". Both reactions occur with electrons derived from the ligand set. Mechanistic studies suggest a single, two electron step is responsible for the bond-formation. Similarly, [CoIII(ap)2]- reacts with alkyl halides to pseudo-oxidatively add the alkyl at the cobalt center. The product of the reaction can be isolated and fully characterized and was found to be best assigned as CoIII(alkyl)(isq)2. This assignment indicates that the reaction occurs, again, with the new bond formed with two electrons formally derived from the ligand set and with no change in oxidation state at the metal center. Mechanistic investigations of the pseudo-oxidative addition suggest the reaction is SN2-like. The reaction occurs with a wide scope of alkyl halides, including those containing beta-hydrogens. The cross-coupling reaction of CoIII(alkyl)(isq)2 with RZnX forms a new carbon-carbon bond. Similarly, the two electron oxidized complex [CoIII(CH3CN)(isq)2]+ reacts with organozinc reagents to couple two carbon nucleophiles and form a new carbon-carbon bond. Both reactions are successful with both sp2 and sp3 carbons. When followed substoichiometrically, the homocoupling reaction can be observed to form CoIII(alkyl)(isq)2. This indicates that the homocoupling and cross-coupling reactions proceed by the same mechanism. However, both reactions have low yields. The yield of the reactions are decreased by steric bulk of the alkyl or aryl fragments or around the metal center created by substituents on the ligand. Also, while the steric congestion disfavors the addition of the first alkyl fragment, the addition of the second alkyl fragment and subsequent rapid elimination of the coupling product is almost completely inhibited. This result also implies that the coupling of the two alkyl fragments is entirely inner-sphere requiring installation of both for coupling. In a complementary study, use of bidentate or tridentate stabilizing ligands in combination with one redox-active catechol-derived or amidophenol-derived ligand was investigated. With the synthesis of (triphos)CoII(cat) and the one electron oxidized [(triphos)CoII(sq)]+, it is evident that the oxidation occurs at the ligand and not the metal. Reaction of (triphos)CoII(cat) with a Cl+ reagent generated a new material which we tentatively describe as (triphos)CoIII(Cl)(sq). This implies that the two electrons used to create the new cobalt-halide bond are derived from both the ligand and the metal, one from each. We believe the complex is unreactive with organic halides due to the steric bulk surrounding the metal center. Similar cobalt complexes containing tridentate or bidentate phosphine ligands or a tridentate pyrazol ligand in combination with a catechol-derived or amidophenol-derived ligand resulted in unsuccessful synthesis or unstable complexes. Throughout the course of both of these studies, steric crowding at the metal center is a problem disfavoring the facilitated reactivity. We have however shown that the amidophenol ligands have favorable molecular orbital overlap with the cobalt to act as an electron reservoir and facilitate reactivity at the metal center. We have also shown that this combination can create a proclivity to facilitate multi-electron reactions at the metal that is naturally prone to radical reactions.

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46

Mallouris, Michael. "Metal complexes of cadmium (II) with thiol-organic and thiol-peptide ligands related to metallothioneins." Thesis, University of Surrey, 1991. http://epubs.surrey.ac.uk/844627/.

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Metallothionein complexes are of a complex nature and have yet to be fully characterised. The work in this thesis concentrates on the complexation of oligopeptide fractions similar to those in thionein with cadmium (II) so as to simulate the complexation sites in the protein and to help clarify the most likely points of attachment of the metal. Complexes of related ligands have also been investigated. In Chapters 2-5 the preparation of various types of ligands, their complexes with cadmium (II) and the solution behaviour of these complexes are described. Cadmium (II) forms octahedral and pseudoctahedral complexes of the type CdL2X2 or CdLX2 (X = halide) with non-thiol ligands such as pyridine, diaminodithiaoctane, 1,3-bis-(2-aminoethyl)-1,3-propanediamine, the Schiff's base 2-hydroxyacetophenoneethylenediimine, and dioxocyclam. In these complexes the ligand complexation sites are N or/and O atoms with the halides acting as bridging ligands. Ligands which contain thioether donor sites only, e.g. tetrathiadioxatricyclohexacosane, do not form complexes with cadmium (II), but if another coordinating group is present in the same ligand, e.g. NH2 or COOH, complexes are readily formed with likely involvement of the thioether group in coordination. Hence the complexes CdL2 and CdLCl were obtained with S-benzyl-L-cysteine and S-benzyl-L-cysteine ethyl ester respectively. Monocarboxylate monothiol ligands, e.g. cysteine and 2-thiolethanoic acid, form the complexes [Cd(HL)X]n in ethanol and [CdL]n in water in which X = halide, thiolate groups or carboxylate groups act as bridging ligands. In case of dithiolate ligands such as 1,2-ethanedithiol, 1,3-propanedithiol, trans-1,2-dithiolcyclohexane and 1,4,8,11-tetrathiaunedecane polynuclear complexes form in which all the S atoms complex to one metal and some are also involved in bridging. Biological thiol ligands such as L-cysteine and D-penicillamine also form polymeric type complexes with cadmium (II) of formulae [Cd(HL)X]n and [Cd(L)]n. A number of peptide complexes of cadmium (II) have been isolated. These include [Cd(H2L)Cl]n and [Cd3L2]n where H3L is glutathione; Cd2(HL)Cl3 and Cd2LCl2 where H2L is gly-cys; Cd2(HL)Cl2 and Cd(L)Cl where H3L is cys-cys; and CdL.xH20 where H2L is gly-cys-gly, gly-cys-ala, gly-cys-val, leu-cys-leu and val-cys-val-val. Dissociation and complex formation equilibria involving a number of cysteine-containing tri- and tetra-peptide ligands were investigated by potentiometric methods and the data analysed using the "MINIQUAD" computer program. The ligands investigated were gly-cys-AA (AA = gly, ala, val), val-cys-val, thr-cys-val, asp-cys-val, leu-cys-leu, val-val-cys-val and val-cys-val-val (their synthesis is described in Chapter 4). At ligand to metal ratios of 1:1 the main complex species in solution are LMH (111), LM (110) and LMOH (11-1) the last of these being formed as a result of deprotonation of an aquo ligand. Peptide ligands containing a thiolate and two carboxyl groups such as asp-cys-val form higher stability constants than those with no thiolate or carboxyl group such as gly- gly-gly or those with a thiolate group but without a side chain carboxylate such as val-cys-val. This indicates that stronger complexes between Cd(II) and cysteinyl peptides will be formed when a coordinating group such as CO2 is present in the ligand side chain. The major coordinating sites are therefore most probably the thiolate, carboxyl and terminal amino (when available) groups. Likely structures for the complexes formed in solution are proposed.

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47

Yates, Andrew Stephen. "Fluorescent cannabinoids : strategies towards the synthesis of fluorescently labelled CB2 receptor ligands." Thesis, University of Nottingham, 2005. http://eprints.nottingham.ac.uk/10107/.

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An increased understanding of the peripheral cannabinoid receptor (CB2) is required due to the CB2 receptor's emerging involvement in a number of disease states. New fluorescent technologies are capable of generating information about the CB2 receptor systems that has been unachievable using existing pharmacological methods i.e. radioisotope techniques. Our work, to develop fluorescently labelled CB2 receptor ligands, will provide cannabis researchers a unique pharmacological tool to use in conjunction with these emerging fluorescent technologies. This will aid the understanding of cellular actions of cannabinoids and accelerate the discovery of novel CB2 selective drugs. We report on the design, synthesis, and biological evaluation of novel fluorescent ligands targeted towards the CB2 receptor. The fluorescent ligands were designed and synthesised by conjugating recognized high affinity selective CB2 ligands (JTE2-3, JTE2-6 & JWH015) to appropriate fluorescent dyes via a chemical linker. Positioning of the fluorescent dye upon the pharmacophore was guided using established SAR data and supplemented by in-house molecular modelling experiments. Our results showed that modification of JTE2-3 and JTE2-6 with dansyl and BODIPY fluorophores resulted in fluorescent ligands which displayed poor affinity to the CB2 receptor and consequently were unsuccessful when used in fluorescent confocal microscopy experiments. Furthermore, our studies revealed important species selectivity, associated with JTE2-3, which was previously unrecognised. Using de novo drug design on JWH015, we synthesised and tested a 3-naphthyl modified fluorescent conjugate, 3-Gly-NBD-JWH015. The compound retained limited affinity to the CB2 receptor, but fluorescent confocal microscopy did not reveal specific receptor membrane binding. Further experiments using 3-naphthyl precursor compounds, displaying less bulky 3-substituents, demonstrated that limited modification to the 3-naphthyl position of JWH015 was tolerated and provided a first insight to the SAR at this position.

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48

Vernetti, Samantha Sizemore. "Two New Resorcinarenes: A Pyridine & Acetic Acid Ligand for Metal Coordination and a Deep-Cavity Nitroquinoxaline Resorcinarene." Diss., CLICK HERE for online access, 2006. http://contentdm.lib.byu.edu/ETD/image/etd1279.pdf.

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49

Chiu, Winnie Wai Hang. "Metal complexes with sulfur and selenium donor ligands /." View abstract or full-text, 2009. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202009%20CHIU.

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50

Ridd, Thomas Ian. "Reactions and ligand binding properties of cytochrome P450." Thesis, University of Surrey, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308553.

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Dissertations / Theses on the topic 'Ligards (Biochemistry)'

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