Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production

FEBS J. 2010 May;277(9):2096-108. doi: 10.1111/j.1742-4658.2010.07623.x. Epub 2010 Mar 22.

Abstract

The protein arginine methyltransferase (PRMT) family of enzymes catalyzes the transfer of methyl groups from S-adenosylmethionine to the guanidino nitrogen atom of peptidylarginine to form monomethylarginine or dimethylarginine. We created several less polar analogs of the specific PRMT inhibitor arginine methylation inhibitor-1, and one such compound was found to have improved PRMT inhibitory activity over the parent molecule. The newly identified PRMT inhibitor modulated T-helper-cell function and thus may serve as a lead for further inhibitors useful for the treatment of immune-mediated disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Histones
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / immunology
  • Interleukin-4 / biosynthesis*
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Methylation
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Promoter Regions, Genetic
  • Protein-Arginine N-Methyltransferases / antagonists & inhibitors*
  • Structure-Activity Relationship
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / drug effects*
  • T-Lymphocytes, Helper-Inducer / immunology*

Substances

  • Enzyme Inhibitors
  • Histones
  • Interleukin-4
  • Interferon-gamma
  • Protein-Arginine N-Methyltransferases