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 9 of 9 for “"orthosteric site"”.
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Protein-Protein Interactions with Serotonin G Protein Coupled Receptors: Novel Targets for Neurotherapeutics Drug Discovery
… inverse agonists and antagonists that target the orthosteric site. While this approach has yielded several important medications, the development of selective orthosteric ligands is challenging and has led to the loss of many promising therapeutic candidates from the drug development pipeline due …
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Building a rational model for the identification of allosteric sites
… that is induced by the binding of a ligand at a site distinct from the orthosteric site.1, 2 Interaction of a small molecule with these sites can bring greater selectivity as they are not conserved within a family and therefore could lead to new opportunities in drug discovery. Unfortunately, no …
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Rapid analysis of pharmacology for infectious diseases.
… aeruginosa</em> and eukaryotic parasites <em>Trypanosoma brucei, Trypanosoma cruzi</em>, <em>Leishmania braziliensis, Leishmania infantum, Leishmania major</em> and <em>Schistosoma mansoni</em>.<br/> In order to identify druggable and selective targets a domain-based approach to …
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The Characterisation Of Bee Nicotinic Acetylcholine Receptors
… we show that species-specific target site variation in the α1 subunit between three species of bees (Apis mellifera, Bombus terrestris and Bombus impatiens) causes a significant change in the efficacious properties of clothianidin, without effecting the pharmacology of the endogenous …
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Bioorthogonal Tethering of Drug Fragments to Engineered G Protein-Coupled Receptors
… on the receptor that do not directly impact the orthosteric site for agonist ligands, but still tune downstream signaling pathways. But identifying and validating allosteric ligands remains difficult partly due to the dynamic nature of GPCRs in native membranes. Of the more than 3700 distinct …
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Regulation of cAMP-Dependent Gene Expression in Airway Epithelial Cells: A Transcriptional and Pharmacodynamic Analysis
… in retention time of a compound near the orthosteric site of the receptor. In the context of obstructive lung diseases LABAs are established bronchodilators. The data presented in this thesis demonstrate that these drugs alone and in combination with a PDE4 inhibitor also have significant …
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Modulation of cyclic adenosine monophosphate (cAMP) signalling and its therapeutic potential: pharmacological characterisation of PDE inhibitors
… known as PDE10A inhibitors, are bound at the orthosteric site of A2AR. To validate the computational results, these compounds were characterised using NanoBRET-based ligand binding studies with HEK293T expressing Nluc-A2AR and functional assays in lung cancer cell lines and glioma/glioblastoma …
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Investigating small-molecule inhibitors of platelet aggregation
… crystal structure of P2Y12 has revealed that the orthosteric site is composed of two sub-pockets. This thesis had two complementary aims: 1) to further understand the mechanism of action of cangrelor – the most recently approved, and only intravenously acting P2Y12 antagonist; and 2) to discover …
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Molecular Modeling And Synthesis For New Opioid Analgesics generations [Modellazione molecolare e sintesi per nuove generazioni di analgesici oppioidi]
Questa tesi di dottorato è incentrata sulla progettazione, la sintesi e la valutazione di nuovi agonisti selettivi per il recettore mu-opioide (MOR) che puntano a un sito di legame ortosterico alternativo. A differenza dei derivati convenzionali della morfina e dei composti a base di benzomorfano, …