Diazomethyl ketone substrate derivatives as active-site-directed inhibitors of thiol proteases. Papain.

Abstract:

:The diazomethyl ketones of z-Phe-Phe inactivate papain by a stoichiometric reaction at the active-center thiol. Since the reagents are stable in mercaptoethanol, their reaction with papain is judged to be the result of complex formation characteristic of affinity-labeling reagents. The diazomethyl ketones react by a mechanism different from that of chloromethyl ketones, since the pH dependence of their inactivation of papain is different, the rate increasing with decreasing pH. This relationship has been observed in other cases, such as in the reaction of azaserine with glutamine amidotransferases [Buchanan, J. M. (1973), Adv. Enzmol. Relat. Areas Mol. Biol. 39, 91], and is interpreted as an indication of reaction with a thiol group in its protonated form.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Leary R,Larsen D,Watanabe H,Shaw E

doi

10.1021/bi00645a033

subject

Has Abstract

pub_date

1977-12-27 00:00:00

pages

5857-61

issue

26

eissn

0006-2960

issn

1520-4995

journal_volume

16

pub_type

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