Potent and selective inactivation of cysteine proteinases with N-peptidyl-O-acyl hydroxylamines

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Potent and selective inactivation of cysteine proteinases with N-peptidyl-O-acyl hydroxylamines.

A series of N-peptidyl-O-acyl hydroxylamines was synthesized and tested as inactivators of cysteine proteinases. Depending on the structure of the peptidyl residue of the inhibitors, rapid and complete irreversible inactivation of the lysosomal cathepsins, B, L and S, may be achieved. The most effective inhibitors display second-order rate constants of the inactivation in the range 10(5)-10(6) ...

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Mechanism of cysteine protease inactivation by peptidyl epoxides.

Peptidyl epoxides are time- and concentration-dependent selective cysteine protease inhibitors. The lack of recovery of enzymic activity and the retention of 1 molar equivalent of radioactive inhibitor associated with the enzyme on dialysis, shown in this study, indicate that they form a covalent irreversible equimolar complex with the enzyme. It is also shown that the peptidyl epoxide inhibito...

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Homology within the N-terminal extension of cysteine proteinases.

It is now well established that the cysteine proteinases of plants (e.g. papain, actinidin, bromelain) and animals (e.g. cathepsins B, H and L) are homologous (see Takio et al., 1983) and almost certainly evolved from a common ancestral protein. For all but one of the cysteine proteinases sequenced to date the N-terminal residues can be exactly aligned with one another at a distance of 25-29 re...

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Cysteine proteinases and the pathogenesis of amebiasis.

Amebiasis is a major cause of morbidity and mortality throughout the tropical world. Entamoeba histolytica is now recognized as a separate species from the morphologically identical E. dispar, which cannot invade. Cysteine proteinases are a key virulence factor of E. histolytica and play a role in intestinal invasion by degrading the extracellular matrix and circumventing the host immune respon...

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Inactivation of papain by antithrombin due to autolytic digestion: a model of serpin inactivation of cysteine proteinases.

Cross-class inhibition of cysteine proteinases by serpins differs from serpin inhibition of serine proteinases primarily in that no stable serpin-cysteine proteinase complex can be demonstrated. This difference in reaction mechanism was elucidated by studies of the inactivation of the cysteine proteinases, papain and cathepsin L, by the serpin antithrombin. The two proteinases were inactivated ...

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ژورنال

عنوان ژورنال: Biochemical Journal

سال: 1989

ISSN: 0264-6021,1470-8728

DOI: 10.1042/bj2630861