Novel allosteric modulators of G protein-coupled receptors

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Abstract

G protein-coupled receptors (GPCRs) are allosteric proteins, because their signal transduction relies on interactions between topographically distinct, yet conformationally linked, domains. Much of the focus on GPCR allostery in the new millennium, however, has been on modes of targeting GPCR allosteric sites with chemical probes due to the potential for novel therapeutics. It is now apparent that some GPCRs possess more than one targetable allosteric site, in addition to a growing list of putative endogenous modulators. Advances in structural biology are also shedding new insights into mechanisms of allostery, although the complexities of candidate allosteric drugs necessitate rigorous biological characterization.
Original languageEnglish
Pages (from-to)19478-19488
Number of pages11
JournalJournal of Biological Chemistry
Volume290
Issue number32
DOIs
Publication statusPublished - 2015

Cite this

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abstract = "G protein-coupled receptors (GPCRs) are allosteric proteins, because their signal transduction relies on interactions between topographically distinct, yet conformationally linked, domains. Much of the focus on GPCR allostery in the new millennium, however, has been on modes of targeting GPCR allosteric sites with chemical probes due to the potential for novel therapeutics. It is now apparent that some GPCRs possess more than one targetable allosteric site, in addition to a growing list of putative endogenous modulators. Advances in structural biology are also shedding new insights into mechanisms of allostery, although the complexities of candidate allosteric drugs necessitate rigorous biological characterization.",
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Novel allosteric modulators of G protein-coupled receptors. / Gentry, Patrickv R; Sexton, Patrick M; Christopoulos, Arthur.

In: Journal of Biological Chemistry, Vol. 290, No. 32, 2015, p. 19478-19488.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Christopoulos, Arthur

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