Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitors.

Journal of the American Chemical Society
Arun K GhoshJordan Tang

Abstract

Structure-based design, synthesis, and X-ray structure of protein-ligand complexes of memapsin 2 are described. The inhibitors are designed specifically to interact with S2- and S3-active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 6 has exhibited exceedingly potent inhibitory activity against memapsin 2 and selectivity over memapsin 1 (>3800-fold) and cathepsin D (>2500-fold). A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D.

References

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Apr 12, 2000·Journal of the American Chemical Society·Arun K GhoshJordan Tang

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Citations

Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Arun K GhoshJordan Tang
Jun 29, 2007·Expert Reviews in Molecular Medicine·Jean-Christophe Rochet
Sep 26, 2012·Journal of Chemical Information and Modeling·Sandro CosconatiArthur J Olson
Dec 24, 2011·Acta Crystallographica. Section D, Biological Crystallography·Yechun XuJoel L Sussman
Apr 2, 2011·Future Medicinal Chemistry·Gisbert SchneiderPetra Schneider
Jul 25, 2013·Journal of Biomolecular Structure & Dynamics·Lucas Joel GutiérrezHéctor Armando Baldoni
Jun 2, 2017·Journal of Computational Chemistry·Nicolas Chéron, Eugene I Shakhnovich
Apr 23, 2016·Chemical Communications : Chem Comm·Yongjin KimJaiwook Park
May 8, 2008·Chemistry : a European Journal·Shuichi NakamuraTakeshi Toru
Jul 18, 2009·Chemistry : a European Journal·Marian Zajac, René Peters
Apr 3, 2014·Chemical Society Reviews·Arun K Ghosh, Heather L Osswald
Jan 25, 2020·International Journal of Molecular Sciences·Varnavas D MouchlisAntreas Afantitis
May 19, 2011·Proteins·Steven A Spronk, Heather A Carlson
Jan 11, 2019·Medicinal Research Reviews·Nalini SchaduangratChanin Nantasenamat
Jul 28, 2019·Medicinal Research Reviews·Nour M Moussa-PachaTaleb H Al-Tel
Apr 17, 2007·Bioorganic & Medicinal Chemistry·Florian ManzenriederHorst Kessler
Jan 8, 2015·Journal of Medicinal Chemistry·Arun K Ghosh, Margherita Brindisi

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