Poststatin, a new inhibitor of prolyl endopeptidase. VI. Endopeptidase inhibitory activity of poststatin analogues containing pyrrolidine ring.
Several pyrrolidine-containing analogues of poststatin were synthesized and examined for their inhibitory activity against prolyl endopeptidase and cathepsin B in vitro. Replacement of the postine residue with 2-oxo-2-(2-pyrrolidinyl)acetic acid increased the selectivity and inhibitory activity against prolyl endopeptidase. Benzyloxycarbonyl-L-phenylalanyl-(S)-2-oxo-2- (2-pyrrolidinyl)acetyl-D-phenylalanine was about 46 times as active to propyl endopeptidase as natural poststatin.
Tsuda
M
M
Institute of Microbial Chemistry, Tokyo, Japan.
Muraoka
Y
Y
Someno
T
T
Nagai
M
M
Aoyagi
T
T
Takeuchi
T
T
D002401:Cathepsin B / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000085822:Prolyl Oligopeptidases; D011759:Pyrrolidines / Q000737:chemistry*; D012697:Serine Endopeptidases / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; C071400:poststatin; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D002401:Cathepsin B; C032519:pyrrolidine