Abstract
Memapsin 2 (beta-secretase) is one of two proteases that cleave the beta-amyloid precursor protein (APP) to produce the 40-42 residue amyloid-beta peptide (Abeta) 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Crystallography, X-Ray
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Drug Design
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Endopeptidases
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Humans
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Models, Molecular
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Molecular Weight
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Protease Inhibitors / chemical synthesis*
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Protease Inhibitors / chemistry
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Structure-Activity Relationship
Substances
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OM99-2
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Oligopeptides
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Protease Inhibitors
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE2 protein, human
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BACE1 protein, human