Abstract
[reaction: see text] Novel tripeptide-derived peptidomimetics 1, 7ab, and 8ab, inspired by templates generated by the structure-generating program GrowMol, were synthesized, shown to inhibit Rhizopus chinensis pepsin, and found by X-ray crystallography to bind to the enzyme in the GrowMol-predicted mode. Repetitive evaluation of the computer-generated templates for synthetic feasibility and optimal enzyme interactions led to the designed compounds.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aspartic Acid Endopeptidases / antagonists & inhibitors*
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Aspartic Acid Endopeptidases / chemistry*
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Aspartic Acid Endopeptidases / metabolism
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Computer Simulation
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Crystallography, X-Ray
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Drug Design
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Molecular Mimicry
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Peptides / chemical synthesis
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Peptides / chemistry*
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Peptides / metabolism*
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Predictive Value of Tests
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Protease Inhibitors / chemical synthesis
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Protease Inhibitors / chemistry*
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Protease Inhibitors / metabolism*
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Protein Conformation
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Structure-Activity Relationship
Substances
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Peptides
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Protease Inhibitors
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Aspartic Acid Endopeptidases
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rhizopuspepsin