Inactivation of Calpain I and Calpain II by Specificity-Oriented Tripeptidyl Chloromethyl Ketones
Three new tripeptidyl chioromethyl ketones, Leu-Leu-XCH2Cl, with X representing Phe, Tyr, or Lys, were synthesized and their potencies to inactivate calpains I and II were compared. They were designed to fulfil the specificity requirement of calpains established recently. When compared in terms of t...
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Published in | Journal of biochemistry (Tokyo) Vol. 99; no. 1; pp. 173 - 179 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Oxford
Oxford University Press
01.01.1986
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Subjects | |
Online Access | Get full text |
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Summary: | Three new tripeptidyl chioromethyl ketones, Leu-Leu-XCH2Cl, with X representing Phe, Tyr, or Lys, were synthesized and their potencies to inactivate calpains I and II were compared. They were designed to fulfil the specificity requirement of calpains established recently. When compared in terms of the dose for 50% inactivation, Leu-Leu-PheCH2Cl was the strongest inactivator, being 500–600 times more effective than tosyl-PheCH2Cl and 5–14 times more than N-[N-(L-3-trans-carboxyoxiran-2-carbonyl)-L-leucyl]agmatine (E-64). The potency toward calpain, either I or II, decreased in the order Phe > Tyr > Lys derivatives > E-64, whereas that toward papain was E-64 > Lys > Phe > Tyr derivatives. From the determined kinetic parameters, the Phe derivative was 18.3 and 16.6 times more effective than E-64 on calpains I and II, respectively. Likewise, the rate of the alkylation reaction by these chloromethyl ketones with calpain I was 2–4 times greater than that with calpain II. Leu-Leu-PheCH2Cl and its N-dansylated product should be useful for highly selective affinity labeling of calpains I and II. |
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Bibliography: | istex:93BF5C2692C71B702181CDB9F06FD5A9FB24DAD2 1This work was supported in part by Grants-in-Aid for Scientific and Cancer Research from the Ministry of Educa tion, Science and Culture of Japan. 4To whom correspondence should be addressed ArticleID:99.1.173 ark:/67375/HXZ-1JD5D4NF-1 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0021-924X 1756-2651 |
DOI: | 10.1093/oxfordjournals.jbchem.a135457 |