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 11 of 11 for “"allosteric inhibitors"”.
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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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DISCOVERY AND BIOPHYSICAL CHARACTERIZATION OF ALLOSTERIC INHIBITORS OF FACTOR XIa (FXIa)
… agents due to its relative safety. A number of inhibitors which target the active site of FXIa have been reported but to our knowledge there have been no inhibitors which act via an allosteric mechanism. The aim of this project was to screen for allosteric inhibitors of FXIa from of pool of …
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The Mechanism of N10-Formyltetrahydrofolate Synthetase. Use of Human Thymidylate Synthase Variants to Characterize Asymmetric Ligand Binding and to Identify Novel Allosteric Inhibitors.
… variant of hTS allows for the development of allosteric ligands as potential drug candidates, which will not only help stabilize the inactive conformation of hTS, but could also lead to decreased drug resistance in chemotherapy patients. Allosteric inhibition studies lead to the investigation …
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Computational and Pharmacological Approaches to Design Novel Allosteric Thymidylate Synthase Inhibitors
<p>The goal of this research is to develop new allosteric thymidylate synthase (TS) inhibitors in an effort to reduce cancer drug resistance. Resistance is associated with elevation in TS levels upon exposure to active site targeted drugs. Human TS exists in conformational equilibrium between …
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Leveraging Local Perturbations to Map Allosteric Networks of Phosphatases
… highly validated as a therapeutic target but no allosteric inhibitors have been approved for clinical use. This is largely because our understanding of the mechanisms underlying allostery in PTP1B remains limited, despite the discovery of putative allosteric sites in PTP1B.</p> <p>In the work …
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Signalling mechanisms of the tyrosine phosphatase SHP2 upstream of Ras
… therefore an important therapeutic target, with allosteric inhibitors ‘locking’ SHP2 in its autoinhibited state currently in clinical trials. However, the efficacy of such allosteric inhibitors is significantly reduced by strongly activating mutations, which account for 50% of SHP2 variants …
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Computational Molecular Docking Studies of Small Molecule Inhibitors With the SARS-CoV-2 Spike Protein Variants: In-Silico Drug Discovery Using Virtual Screening and Drug Repurposing Approaches
… on the spike protein as a target for potential inhibitors. We explore two methods of inhibiting spike function, allosteric inhibition and direct inhibition. In the study of allosteric inhibition, we screened two compound libraries against two allosteric sites. In the study of direct inhibition, …
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Elucidating Isoform Specific Roles of Calpain-1 and Calpain-2 in Breast Cancer
… and describe a biosensor to screen for allosteric inhibitors of calpain-1 and calpain-2.
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Calpain inhibitor design inspired by the natural inhibitor calpastatin
… great interest and medical relevance to design inhibitors that can specifically target calpain without interfering with the other numerous cellular cysteine proteases. The cytosolic and ubiquitous calpains-1 and -2 have a naturally occurring and specific inhibitor, calpastatin, which binds with …
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Targeting final steps of sugar nucleotide biosynthetic pathway against <i>Aspergillus fumigatus</i>
… synthesize β-1,3 glucan from UDP-Glc. Although inhibitors of other glycosyltransferases (e.g. chitin synthases) also exhibit antifungal activity, only echinocandins have been approved for the treatment of aspergillosis. This is due to intrinsic drawbacks of targeting glycosyltransferases. …
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Computer-Aided Design of Ligands at Multiple Protein Targets for Multifactorial Diseases
… proteins/multiple binding sites including allosteric ligands. Calpain-1, a challenging target, was selected to develop and evaluate computational approaches to the discovery of novel ligands. Current selective calpain-1 inhibitors are reported to bind to an allosteric site and their mode of …