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

Bioorg Med Chem. 2014 Sep 1;22(17):4602-8. doi: 10.1016/j.bmc.2014.07.028. Epub 2014 Jul 25.

Abstract

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.

Keywords: ABPP probe; Activity-based protein profiling; Agmatine catabolism; Agmatine deiminase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Affinity Labels / chemical synthesis
  • Affinity Labels / chemistry*
  • Drug Design*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Hydrolases / chemistry*
  • Hydrolases / metabolism*
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry*
  • Molecular Structure
  • Stereoisomerism
  • Streptococcus mutans / enzymology*
  • Substrate Specificity

Substances

  • Affinity Labels
  • Fluorescent Dyes
  • Molecular Probes
  • Hydrolases
  • agmatine deiminase