The development and characterization of a chemical probe targeting PRMT1 over PRMT5

Bioorg Med Chem. 2019 Jan 1;27(1):224-229. doi: 10.1016/j.bmc.2018.12.001. Epub 2018 Dec 4.

Abstract

Protein arginine methyltransferases (PRMTs) are a family of mammalian enzymes catalyzing the symmetric dimethylation (Type I), asymmetric dimethylation (Type II), or monomethylation (Type III) of arginine residues within proteins. This family is composed of 11 isozymes, however the vast majority of asymmetric and symmetric dimethylation in mammals is completed by either PRMT1 or PRMT5, respectively. In recent years, a number of chemical probes targeting this family of enzymes have been developed, but the majority of these probes lack isozyme specificity. Herein, we report the development of a chemical probe, based on a non-natural peptide sequence, which specifically labels PRMT1 over PRMT5 with high selectivity and sensitivity.

Keywords: ABPP; Activity based probe; Arginine; Chemical probe; Protein arginine methyltransferase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Enzyme Assays
  • Isoenzymes / analysis
  • Isoenzymes / chemistry*
  • Kinetics
  • Limit of Detection
  • Methylation
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry*
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein-Arginine N-Methyltransferases / analysis
  • Protein-Arginine N-Methyltransferases / chemistry*
  • Substrate Specificity

Substances

  • Isoenzymes
  • Molecular Probes
  • Peptides
  • Protein-Arginine N-Methyltransferases