The existence of a second allosteric site on the M1 muscarinic acetylcholine receptor and its implications for drug design

L. Michel Espinoza-Fonseca; José G. Trujillo-Ferrara

doi:10.1016/j.bmcl.2005.11.097

The existence of a second allosteric site on the M₁ muscarinic acetylcholine receptor and its implications for drug design

L. Michel Espinoza-Fonseca, José G. Trujillo-Ferrara

Escuela Superior de Medicina (ESM)

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

Fully flexible docking of KT5720, an allosteric modulator of the muscarinic receptors, was performed on a dynamic model of the M₁ muscarinic acetylcholine receptor. The results confirmed the existence of a second allosteric site, located on the intracellular face of the receptor. These results would be beneficial for the design of modulators of this receptor to be used as an effective alternative against the Alzheimer's disease.

Original language	English
Pages (from-to)	1217-1220
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	16
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2005.11.097
State	Published - 1 Mar 2006

Keywords

Alzheimer's disease
Blind docking
M muscarinic receptor
Molecular dynamics simulations
Multiple allosteric sites
Relax complex scheme
Staurosporine derivatives

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10.1016/j.bmcl.2005.11.097

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abstract = "Fully flexible docking of KT5720, an allosteric modulator of the muscarinic receptors, was performed on a dynamic model of the M1 muscarinic acetylcholine receptor. The results confirmed the existence of a second allosteric site, located on the intracellular face of the receptor. These results would be beneficial for the design of modulators of this receptor to be used as an effective alternative against the Alzheimer's disease.",

keywords = "Alzheimer's disease, Blind docking, M muscarinic receptor, Molecular dynamics simulations, Multiple allosteric sites, Relax complex scheme, Staurosporine derivatives",

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note = "Funding Information: The authors thank Edward C. Hulme for kindly providing the coordinates of the homology model of the M 1 muscarinic receptor and Asya Varbanova for her careful review of the manuscript. This work was supported by grants from CONACYT and CGPI-IPN to J.G.T.F and from the Department of Biochemistry, Structural Biology and Biophysics, University of Minnesota, and the Minnesota Supercomputing Institute to L.M.E.F.",

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AU - Trujillo-Ferrara, José G.

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KW - Multiple allosteric sites

KW - Relax complex scheme

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The existence of a second allosteric site on the M₁ muscarinic acetylcholine receptor and its implications for drug design

Abstract

Keywords

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