Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 41 for “"allosteric modulators"”.
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Influence of Peptide Allosteric Modulators on Agonist Bias at Class B1 G Protein-Coupled Receptors
… and inactive receptor conformations through allosteric mechanisms. The consequences of SNPs in N-terminal and C-terminal regions of GLP1R, glucagon receptor (GCGR), secretin receptor (SCTR), and corticotropin-releasing factor receptor type 1 (CRF1) were therefore investigated. Whilst some …
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Design, Synthesis, and Pharmacological Characterization of Serotonin (5-HT) 5-HT2C Receptor (5-HT2CR) Positive Allosteric Modulators
… pharmacologically evaluated as 5-HT2CR positive allosteric modulators (PAMs). Several analogues potentiated intracellular calcium release by 5-HT in h5-HT2CR-CHO cells. Several compounds exhibited a favorable overall pharmacokinetic profile and modulated 5-HT2CRassociated behaviors (e.g., …
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Synthesis of sila-analogs and silicon-containing derivatives of drugs and development and application of the Si-2,4,6-trimethoxyphenyl moiety as a novel protecting group in organosilicon chemistry
… (disila-CMPD1), a series of silicon-based allosteric modulators of muscarinic receptors, and a partial synthesis of sila-gabapentin. Crystal structure data of rac-sila-venlafaxine hydrochloride, (R)-sila-venlafaxine hydrobromide, bexarotene, disila-bexarotene, and disila-AG-045572 …
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Small Molecule Allosteric Modulation of G Protein-Coupled Receptors and Applications in the Pharmacological Targeting of 5-HT2 Receptors
… target GPCRs. Predictably, small molecule allosteric modulation has emerged in recent years as a new means to control GPCR function with numerous examples nearing FDA approval. This body of work begins with a substantive review of drug discovery efforts in the development of Class A GPCR …
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Drug discovery at class A and class B GPCRs
… of this thesis was to discover and improve GIPR allosteric modulators using both in silico and in vitro techniques. This resulted in successful identification of potent and selective GIPR negative allosteric modulators like compound C25, while also investigating the bias of the compounds at …
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Designing Allosteric Inhibitors of Thrombin
… that thrombin may be better regulated through an allosteric process mediated by small molecules binding to either exosite I or II. An appropriately designed allosteric regulator that reduces the procoagulant signal in a finely tuned manner may maintain a delicate balance between procoagulant and …
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Gabab Regulation of Methamphetamine-Induced Associative Learning
… baclofen limit its clinical utility. Positive allosteric modulators (PAMs) of the GABAB receptor augment GABAB receptor signaling without the side effects of the agonist making it a better alternative to agonist therapy.</p><p>The current project sought to determine the role of the GABAB …
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Accelerated simulations and computer-aided drug design of membrane proteins
… and retrospective docking of known positive allosteric modulators (PAMs) to GaMD simulation-derived structural ensembles of the adenosine A1 receptor (A1AR), respectively. Finally, in Chapter 5, I apply LiGaMD to understand the mechanism of ligand recognition by human Angiotensin Converting …
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Molecular Signaling and Agonist Discovery for GPR52
… GPR52 agonists and their mechanism of action as allosteric modulators of ECL2-mediated self-activation. Iterative drug design led to the identification of a new series of GPR52 agonists with improved potency and efficacy. Several of these compounds demonstrated bias for G protein/cAMP signaling …
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A robust machine learning approach for the prediction of allosteric binding sites
Allosteric regulatory sites are highly prized targets in drug discovery. They remain difficult to detect by conventional methods, with the vast majority of known examples being found serendipitously. Herein, a rigorous, wholly-computational protocol is presented for the prediction of allosteric …
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AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance trained rats
… contraction-induced changes in undefined allosteric modulators, and contraction-induced association with other proteins. (Study approved by the IACUC and supported by NIH RO1 AR41438.)
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Studies in GPCR and Chromosomal Control
… small molecule serotonin agonists and positive allosteric modulators targeting the two receptors, as well as peptide mimics of the transmembrane domains to control the receptor associations. Ewing’s Sarcoma is a malignant pediatric cancer found in bones and soft tissues. It is the second most …
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An Investigation into the pharmacology of the ghrelin receptor
… and L-692,429, have been described as ‘ago-allosteric modulators’ of the GRLN-R as, when co-administered with ghrelin, GHRP-6 and L-692,429 were reported to act both as co-agonists (increasing the efficacy of the ghrelin response) and as negative or positive (respectively) regulators of the …
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Novel Modulators of CD39 and CD73
… kinase inhibitors to identify novel modulators of CD39 and CD73, explore their mechanisms of action, investigate their binding sites via in-silico docking, and evaluate the ex-vivo activity of specific CD39 modulators. The malachite green assay was employed for in-vitro screening of …
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The Structural Mechanism of Allosteric Modulation of The Nmda Receptor: A Balance of Tensions
… disorders. Studies targeting the mechanism of allosteric modulation, such as this study, hope to contribute to the understanding of how NMDA receptors are modulated to allow for better drug development.</p> <p>NMDA receptors are obligate heterotetramers, typically composed of glycine-binding …
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NOVEL THERAPEUTIC APPROACHES EMERGING FROM HCN CHANNELS STRUCTURAL AND FUNCTIONAL STUDIES
… We further explore the use of pore blockers and allosteric modulators to restore wild-type-like function in mutant HCN1 channels in vitro, highlighting the potential of precision medicine approaches tailored to mutation-specific phenotypes. Extending these studies ex vivo, we demonstrate that the …
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Studies on rationally designed, allosteric, coagulation inhibitors
Heparin is a natural allosteric modulator, with numerous structural and conformational variations leading to many reports of bleeding complications and variations in anticoagulant effects. A flurry of research has been directed towards understanding this puzzle. This work entails the utilization of …
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Protein-ligand interaction studies and identification of new drug-like hits as cannabinoid receptor modulators
… inverse agonists, and (3) the identification of allosteric site(s) in the CB2 receptor and screening of new CB2 allosteric modulators (AMs).</p> <p>Chapter 1 describes background information on cannabinoids and the endocannabinoid system. Chapter 2 focuses on the structure-activity relationships …
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