Identification of novel specific allosteric modulators of the glycine receptor using phage display

Megan E. Tipps, Jessica E. Lawshe, Andrew D. Ellington, S. John Mihic

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

The glycine receptor (GlyR) is a member of the Cys-loop superfamily of ligand-gated ion channels and the major mediator of inhibitory neurotransmission in the spinal cord and brainstem. Many allosteric modulators affect the functioning of members of this superfamily, with some such as benzodiazepines showing great specificity and others such as zinc, alcohols, and volatile anesthetics acting on multiple members. To date, no potent and efficacious allosteric modulator acting specifically at the GlyR has been identified, hindering both experimental characterization of the receptor and development of GlyR-related therapeutics. We used phage display to identify novel peptides that specifically modulate GlyR function. Peptide D12-116 markedly enhanced GlyR currents at low micromolar concentrations but had no effects on the closely related γ-aminobutyric acid type A receptors. This approach can readily be adapted for use with other channels that currently lack specific allosteric modulators.

Original languageEnglish (US)
Pages (from-to)22840-22845
Number of pages6
JournalJournal of Biological Chemistry
Volume285
Issue number30
DOIs
StatePublished - Jul 23 2010

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