Design, synthesis, and in vitro evaluation of an activity-based protein profiling (ABPP) probe targeting agmatine deiminases

Agmatine deiminases (AgDs) belong to a family of enzymes known as guanidinium group modifying enzymes (GMEs). Many pathogenic bacteria encode an AgD that participates in the catabolism of agmatine (decarboxylated arginine). This catabolism may confer a competitive survival advantage, by virtue of energy production and increased acid tolerance, making this sub-family of enzymes a potential therapeutic target that warrants further study. Herein we report the development of an activity-based protein profiling (ABPP) probe that selectively targets the AgD from Streptococcus mutans. Due to the selectivity and covalent nature of the modification, this probe could prove to be a valuable tool for the study of other AgD family members.

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