title: Aspartic protease inhibitors designed from computer-generated templates bind as predicted.
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.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, 777 Highland Avenue, Madison, Wisconsin 53705, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Ripka
authors.forename: K A
authors.initials: KA
authors.lastname: Satyshur
authors.forename: R S
authors.initials: RS
authors.lastname: Bohacek
authors.forename: D H
authors.initials: DH
authors.lastname: Rich
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D015195:Drug Design; D018716:Molecular Mimicry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011237:Predictive Value of Tests; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; C035794:rhizopuspepsin