New Acyloxymethyl Ketones: Useful Probes for Cysteine Protease Profiling

^§ These authors contributed equally to this work

Abstract

Peptidyl-acyloxymethyl ketones (AOMKs) belong to a class of selective, irreversible inhibitors (activity-based probes) widely used as chemical tools of investigating proteins, for example, in activity-based protein profiling. The synthesis of the AOMKs has always been challenging and current methodologies involve both solution and solid-phase synthesis. Herein, the synthesis of a new scaffold useful for the preparation of peptidyl-AOMKs is reported and it is demonstrated that the new synthetic probes bearing a 4-functionalized 2,6-dimethylbenzoate efficiently inhibit cysteine proteases like cathepsin B.

Key words

acyloxymethyl ketones - activity-based probes - peptidyl-AOMKs - 2,6-dimethylbenzoates - solid-phase peptide synthesis

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