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

doi:10.1021/jm0101803

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

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

236 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 language	English (US)
Pages (from-to)	2865-2868
Number of pages	4
Journal	Journal of Medicinal Chemistry
Volume	44
Issue number	18
DOIs	https://doi.org/10.1021/jm0101803
State	Published - Aug 30 2001

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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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.",

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T2 - Potent inhibitors of human brain memapsin 2 (β-secretase)

AU - Ghosh, A. K.

AU - Bilcer, G.

AU - Harwood, C.

AU - Kawahama, R.

AU - Shin, D.

AU - Hussain, K. A.

AU - Hong, L.

AU - Loy, J. A.

AU - Nguyen, C.

AU - Koelsch, G.

AU - Ermolieff, J.

AU - Tang, J.

PY - 2001/8/30

Y1 - 2001/8/30

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AB - 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.

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

Abstract

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