G-protein-coupled receptor allosterism: the promise and the problem(s)

Arthur Christopoulos, L T May, Vimesh Ashvinkumar Avlani, Patrick M Sexton

Research output: Contribution to journalArticleOther

Abstract

Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor s endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more physiological regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.
Original languageEnglish
Pages (from-to)873 - 877
Number of pages5
JournalBiochemical Society Transactions
Volume32
Issue numberPt 5
Publication statusPublished - 2004
Externally publishedYes

Cite this

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abstract = "Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor s endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more physiological regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.",
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G-protein-coupled receptor allosterism: the promise and the problem(s). / Christopoulos, Arthur; May, L T; Avlani, Vimesh Ashvinkumar; Sexton, Patrick M.

In: Biochemical Society Transactions, Vol. 32, No. Pt 5, 2004, p. 873 - 877.

Research output: Contribution to journalArticleOther

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AU - Christopoulos, Arthur

AU - May, L T

AU - Avlani, Vimesh Ashvinkumar

AU - Sexton, Patrick M

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AB - Allosteric modulators of G-protein-coupled receptors interact with binding sites that are topographically distinct from the orthosteric site recognized by the receptor s endogenous agonist. Allosteric ligands offer a number of advantages over orthosteric drugs, including the potential for greater receptor subtype selectivity and a more physiological regulation of receptor activity. However, the manifestations of allosterism at G-protein-coupled receptors are quite varied, and significant challenges remain for the optimization of screening methods to ensure the routine detection and validation of allosteric ligands.

UR - http://www.ncbi.nlm.nih.gov/pubmed/15494038

M3 - Article

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JO - Biochemical Society Transactions

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SN - 0300-5127

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