From peptides to non-peptide peptidomimetics: design and synthesis of new piperidine inhibitors of aspartic peptidases.
[reaction: see text] The 3-alkoxy-4-arylpiperidine inhibitors of aspartic peptidases are shown to be a new type of non-peptide peptidomimetic inhibitor. These piperidines can be designed from peptide-derived inhibitors by use of a structure-generating program but only after the enzyme active site conformation has been modified in a mechanistically related fashion. New enantioselective syntheses of 3-alkoxy-4-arylpiperidine analogues are described.
Bursavich
M G
MG
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA.
West
C W
CW
Rich
D H
DH
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000737:chemistry; D001665:Binding Sites; D010434:Pepsin A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D000092502:Renin Inhibitors
D016282:Aspartic Acid Endopeptidases; D010434:Pepsin A; D010880:Piperidines; D011480:Protease Inhibitors; D000092502:Renin Inhibitors; C035794:rhizopuspepsin