A Chloroacetamidine-based Inactivator of Protein Arginine Methyltransferase 1: Design, Synthesis, and in Vitro and in Vivo Evaluation

Obiamaka Obianyo, Corey P. Causey, Tanesha C. Osborne, Justin E. Jones, Young-Ho Lee, Michael R. Stallcup, Paul R. Thompson

Research output: Contribution to journalArticlepeer-review

40 Scopus citations
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Abstract

Protein arginine methyltransferases (PRMTs) catalyze the post-translational methylation of arginine residues. PRMT1 is the predominant mammalian isozyme, and is responsible for generating the majority of the asymmetrically dimethylated arginine found in vivo. The dysregulation of this enzyme has been implicated in heart disease and cancer; thus, its inhibition would be useful in the treatment of these diseases. Herein, we describe the most potent PRMT1 inhibitor described to date. This compound, denoted C21, is a chloroacetamidine-containing peptide that is able to irreversibly bind and inactivate the enzyme selectively. We have also shown that the coactivator activity of PRMT1 is selectively inhibited by the compound in cellulo.

Original languageAmerican English
JournalChemBioChem
Volume11
StatePublished - 2010

Disciplines

  • Chemistry

Keywords

  • Cl-amidine
  • Enzymes
  • Inhibitors
  • Protein arginine methyltransferase
  • Transcription

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