Journal
NEUROPHARMACOLOGY
Volume 60, Issue 1, Pages 102-107Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2010.07.002
Keywords
Metabotropic glutamate receptors; Class C GPCR; Orthosteric ligand; Allosteric modulation; Chloride binding site; LIVBP
Categories
Funding
- CNRS
- Comite Parkinson of the Fondation de France [580062]
- Agence Nationale pour la recherche [ANR 05-NEUR-021-04]
- Federation pour la Recherche sur le Cerveau
- Era-net NEURON [ANR-08-NEUR-006-02]
Ask authors/readers for more resources
A recent publication from Ogawa et al. suggested a possible allosteric chloride binding site in the extracellular domain of metabotropic glutamate receptors (mGluRs) by comparison with a similar site found in atrial natriuretic peptide receptor. We simultaneously reported about (S)-PCEP an agonist of subtype 4 mGluR that would bind to a similar pocket, adjacent to the glutamate binding site. Here we disclose LSP1-2093, a new derivative of (S)-PCEP that holds a nitrophenyl substituent. Docking experiments predict that the nitro group binds to the receptor at the putative chloride ion site. It is thus possible to take advantage of this putative chloride binding site to develop new types of mGluR agonists. This pocket is present in the structural family of Leucine Isoleucine Valine Binding Protein that includes class C GPCRs, suggesting that extended agonists may be identified at receptors bearing such a structural domain. (C) 2010 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available