The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B.

The Biochemical journal ·Vol. 253 ·No. 3 ·1988-08-01 ·Pages 751-8

Crawford C, Mason RW, Wikstrom P, Shaw E

Abstract

A series of peptidyldiazomethanes was synthesized and tested as inactivators of the cysteine proteinases calpain II, cathepsin L and cathepsin B. Inactivators that react rapidly and that show a degree of selectivity between the enzymes were identified. Z-Tyr(I)-Ala-CHN2 (where Z represents benzyloxycarbonyl) reacts rapidly with cathepsin L and more slowly with cathepsin B, but does not inhibit calpain II. Z-Leu-Leu-Tyr-CHN2 reacts rapidly with cathepsin L and calpain II but very slowly with cathepsin B. Boc-Val-Lys(epsilon-Z)Leu-Tyr-CHN2 (where Boc represents t-butyloxycarbonyl) reacts more rapidly with calpain II than with cathepsin L or cathepsin B. The discriminating inhibitory effects of these compounds make them potentially useful for investigation of enzyme functions in vivo. The data presented also provide insights into the subsite specificity of calpain.

MeSH Terms

Calpain/antagonists & inhibitors Cathepsin B/antagonists & inhibitors Cathepsin L Cathepsins/antagonists & inhibitors Cysteine Endopeptidases Diazomethane/analogs & derivatives,chemical synthesis,pharmacology Dipeptides/chemical synthesis,pharmacology Endopeptidases Kinetics Oligopeptides/pharmacology Protease Inhibitors/chemical synthesis,pharmacology Structure-Activity Relationship

Chemicals

Dipeptides Oligopeptides Protease Inhibitors benzyloxycarbonyltyrosylalanine diazomethane Diazomethane Cathepsins Endopeptidases Calpain Cysteine Endopeptidases Cathepsin B Cathepsin L

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

Crawford C

Department of Biochemistry, Strangeways Laboratory, Cambridge, U.K.

Mason R W

Wikstrom P

Shaw E

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25 references, click to expand

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Article Info

Journal

The Biochemical journal

Abbr.

Biochem J

ISSN

0264-6021

DOI

10.1042/bj2530751

Published

1988-08-01

Pages

751-8

Language

English

Region

England

NLM ID

2984726R

PMCID

PMC1149367

Subset

External Links

PubMed source DOI: 10.1042/bj2530751 PMC Full Text View journal details

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The design of peptidyldiazomethane inhibitors to distinguish between the cysteine proteinases calpain II, cathepsin L and cathepsin B.

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