title: Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues.
abstract: Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The alpha-ketone was essential and the S configuration was preferable to the R configuration in the beta-substituted-beta-amino-alpha-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)- 3-amino-2-oxovaleryl-D-leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Muraoka
authors.forename: M
authors.initials: M
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Aoyagi
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D002401:Cathepsin B / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D015842:Serine Proteinase Inhibitors; C071400:poststatin; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases; D019272:Leukocyte Elastase; D002401:Cathepsin B