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Molecular Manipulation of G Protein coupled Receptors A New Avenue into Drug Discovery

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Abstract:

During the past 10 years or so, associated with the introduction of molecular biology techniques to G protein coupled receptor (GPCR) research, outstanding progress has been made in understanding the mechanisms of action of these key proteins and their physiological functions. in vivo manipulation of levels of GPCRs using transgenic and gene knock out approaches have been particularly successful in assessing the roles of specific GPCRs in animal physiology.

Drug discovery is aiming to produce highly specific compounds based on subtle definition of receptor subtypes which can best be studied using heterologous expression of wild type or mutated forms of cDNA or genes encoding these proteins. Furthermore, new therapeutic opportunities may be provided by investigation of orphan receptors, the natural ligands for which remain unidentified. Some human diseases have been shown to be associated with rare mutations of GPCRs and the possibility that widely distributed polymorphisms in GPCR genes may allow selective therapeutic strategies for population subgroups is driving the development of the science of pharmacogenetics.

Keywords: G protein coupled receptors; GPCR; GPCR Polymorphisms; Luteinising hormone; Orphan Receptors; Plasma membrane; cDNA; cholecystokinin; gene; ligand bidning domains; neuropeptide Y; thyroid stimulatin hormone

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/0929867003374570

Publication date: September 1, 2000

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

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