Structure-based design: Potent inhibitors of human brain memapsin 2 (β-secretase)

A. K. Ghosh, G. Bilcer, C. Harwood, R. Kawahama, D. Shin, K. A. Hussain, L. Hong, J. A. Loy, C. Nguyen, G. Koelsch, J. Ermolieff, J. Tang

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227 Scopus citations

Abstract

Memapsin 2 (β-secretase) is one of two proteases that cleave the β-amyloid precursor protein (APP) to produce the 40-42 residue amyloid-β peptide (Aβ) in the human brain, a key event in the progression of Alzheimer's disease. On the basis of the X-ray crystal structure of our lead inhibitor (2, OM99-2 with eight residues) bound to memapsin, we have reduced the molecular weight and designed potent memapsin inhibitors. Structure-based design and preliminary structure-activity studies have been presented.

Original languageEnglish (US)
Pages (from-to)2865-2868
Number of pages4
JournalJournal of Medicinal Chemistry
Volume44
Issue number18
DOIs
Publication statusPublished - Aug 30 2001

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ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Ghosh, A. K., Bilcer, G., Harwood, C., Kawahama, R., Shin, D., Hussain, K. A., ... Tang, J. (2001). Structure-based design: Potent inhibitors of human brain memapsin 2 (β-secretase). Journal of Medicinal Chemistry, 44(18), 2865-2868. https://doi.org/10.1021/jm0101803