Affordable Access

deepdyve-link deepdyve-link
Publisher Website

Inhibition of rat liver cathepsins B and L by the peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal and its analogues.

Authors
Type
Published Article
Journal
Journal of Enzyme Inhibition and Medicinal Chemistry
1475-6374
Publisher
Informa UK (Taylor & Francis)
Publication Date
Volume
24
Issue
1
Pages
279–286
Identifiers
DOI: 10.1080/14756360802166921
PMID: 18830882
Source
Medline
License
Unknown

Abstract

Cathepsins B and L belong to the papain superfamily of cysteine proteases and play important roles in various physiological and pathological processes. In the course of studies on their inhibitors, we examined the inhibitory effects of the peptide aldehyde benzyloxycarbonyl-leucyl-leucyl-leucinal (ZLLLal) and its analogues. As a result, rat liver cathepsins B and L were shown to be strongly inhibited by them. The concentration required for 50% inhibition (IC(50)) by ZLLLal was 88 nM for cathepsin B and 163 nM for cathepsin L. Moreover, various analogues of ZLLLal, including 2-furancarbonyl-, nicotinyl-, isonicotinyl- and 4-morpholinylsuccinyl-LLLals, and some acetyl-Pro (AcP)-containing analogues, AcPLLLal and AcPPLLLal, were shown to inhibit both enzymes more strongly than ZLLLal. Among them, isonicotinyl-LLLal was most inhibitory against both cathepsins B (IC(50), 12 nM) and L (IC(50), 20 nM). Several of these inhibitors were indicated to be somewhat more soluble in aqueous media than ZLLLal.

Statistics

Seen <100 times