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 17 of 17 for “"allosteric modulation"”.
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Allosteric Modulation of Metabotropic Glutamate Receptor 5 as a Treatment for Pain
… a selective and potent non-competitive negative allosteric modulator of mGlu5, and previously shown to be safe and effective in clinical trials of human anxiety. I found Fenobam to be analgesic in models of chemical nociception and inflammatory pain. Fenobam was also found to be without analgesic …
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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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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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Role of Microglial α7 Nicotinic Acetylcholine Receptor Positive Allosteric Modulator in Neuroinflammatory Pain Models in Mice
… hypothesized that microglial α7 nAChRs positive allosteric modulation in the hippocampus will decrease neuroinflammatory pain at behavioral, cellular, biochemical, and molecular level. The primary objective of current study was to examine the role of an α7 nAChR positive allosteric modulator …
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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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Characterising the conformational dynamics of β₁-adrenergic receptor activation and G protein coupling
… changes in a highly interconnected allosteric activation network which enables coupling to intracellular signalling partners, including selective coupling to specific G protein α-subtypes. Investigations in solution by nuclear magnetic resonance spectroscopy (NMR) have been utilised …
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Fret-Based Investigations of The Structure-Function Relationships In The Nmda Receptor
… its slow kinetics, its calcium permeability, its allosteric modulation, and its especially important functional roles in synaptic plasticity, excitotoxicity, and more. In recent years, a wealth of structural information has come about describing endpoint structures to high resolution, but such …
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Investigation of structural dynamics and the function of membrane proteins with computational techniques
… binding to the rare PIP2lipids, leads to its allosteric modulation. We believe that this allosteric modulation plays a very important role in the downstream signalling events.Integral membrane proteins in their native environment are also presented. As a major class of integral membrane …
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Cannabinoid Type 2 Receptors Promote Cadherin Switching While Suppressing Cell Migration: A Novel Investigation into Biased GPCR Signaling
… effects may stem from biased agonism and allosteric modulation within the CB2 GPCR, rather than differences in ligand efficacy or stimulus-response coupling. Elucidating the strength and kinetic profile of CB2 agonists in this signaling platform may yield crucial insights into cannabinoid …
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Characterisation of novel alpha1-adrenoceptor ligands
… pocket, but that C7-C11 interacted with a second allosteric site in a bitopic manner. 4-aminoquinoline, C9, C10, and C11 increased the dissociation rate of [3H] prazosin from the α1A-AR, suggesting allosteric modulation. C9 was further characterised and demonstrated to be a negative allosteric …
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Role of group II metabotropic glutamate receptor subtype 2 (mGluR2) in appetitive and consummatory aspects of ethanol reinforcement
… LY379268 (LY37) and selective mGluR2 positive allosteric modulator (PAM) BINA were used to determine the relative contribution of mGlu2 and mGlu3 receptors on EtOH seeking and consumption. Following characterization of the agonist and PAM on EtOH reinforcement, a microinjection study was …
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Structural and molecular determinants of the sensitivity of alpha4beta2 nicotinic acetylcholine receptors to the allosteric ligand desformylflustrabromine
Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. By binding to a site of the receptor distinct from the neurotransmitter binding site, allosteric modulators alter the response of the receptors to …
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Structural and molecular determinants of the sensitivity of alpha4beta2 nicotinic acetylcholine receptors to the allosteric ligand desformylflustrabromine
Allosteric modulation of neuronal nicotinic acetylcholine receptors (nAChRs) is considered to be one of the most promising approaches for therapeutics. By binding to a site of the receptor distinct from the neurotransmitter binding site allosteric modulators alter the response of the receptors to …
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Synthese und Charakterisierung allosterer Modulatoren muscarinischer M2-Rezeptoren : Strukturvariationen der Bis(ammonium)alkan-Verbindung W84
Die vorliegende Arbeit befasst sich mit der Synthese und Charakterisierung allosterer Modulatoren muscarinischer Rezeptoren. Allostere Modulatoren binden an einer topographisch anderen Stelle am Rezeptor als klassische orthostere Liganden und sind so in der Lage, die Dissoziation und die …
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Interactions of insecticidal spider peptide neurotoxins with insect voltage- and neurotransmitter-gated ion channels
… These findings are consistent with a positive allosteric modulation of insect nAChRs to slow receptor desensitisation. The nAChR is a validated insecticidal target for various agrochemical insecticides, including the allosteric modulator spinosyn A. Therefore it is believed that the lethal …
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Aminosubstituierte Terphenyle als neue Leitstruktur für allostere Modulatoren muscarinischer M2-Acetylcholinrezeptoren
Die muscarinischen Rezeptoren sind ein wichtiger Bestandteil des parasympathischen Nervensystems. Sie gehören zur großen Gruppe der G-Protein-gekoppelten Rezeptoren, die nach ihrer Verwandtschaft in drei große Klassen eingeteilt werden können. Die muscarinischen Rezeptoren gehören zur Klasse A, den …
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Single-Molecule Studies of CFTR Gating and Pharmacology
… altered by disease mutations and pharmacological modulation. I first established a model for gating by wild-type CFTR. I found that CFTR exhibits an allosteric gating mechanism in which conformational changes within the NBD-dimerized channel, governed by ATP hydrolysis, regulate chloride …