Drug Discovery in Interacting Proteins
Date du début: 1 août 2010,
Date de fin: 31 juil. 2014
The Pharmaceutical sector is a mainstay of the European economy. However, changing patterns of drug discovery and competition has greatly enhanced the need for a SME sector to produce new drug leads and targets to feed big Pharma pipelines. This application addresses the need by coalescing partners involved in the identification/validation of new targets and in drug design, synthesis and discovery. The focus is on type 2 diabetes, obesity and immune diseases which cause serious disability and reduced life expectancy globally. Dualsystems and NUIM will be involved in the identification/validation of protein interactions involved in the pathway linking retinol binding protein and insulin, through which the former, when elevated in obesity, inhibits responses to the latter thereby contributing to type 2 diabetes. A second project will identify the protein machinery involved in the failure of otherwise active natural mutants of the MC4 receptor to traffic to the cell surface. This failure produces 6-7% of cases of gross genetic obesity. The third project will identify native protein ligands for a new family of G-protein coupled receptors (LNB-GPCRs), deeply implicated in immune-related diseases and cancer. The transfer of knowledge (TOK) involve development and use of yeast 2-hybrid systems to identify putative interactors and of rapid in vitro systems for interacting protein validation. A new yeast-based biosensor system will be advanced from “proof of concept” to the development stage. AFChemPharm focuses on new systems of chemical synthesis. They will work with NUIM on protein modelling, drug design, in silico screening and chemical synthesis to produce selected panels of compounds to screen for “hits” and to optimise into “leads. The TOK and skills acquisition will involve state of the art computational approaches in modelling, drug design and screening, together with their amalgamation with new synthetic processes to tailor/refine design and synthesis.
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