In Situ Generation of a Bisubstrate Analog for Protein Arginine Methyltransferase 1

Tanesha C. Osborne, Rachel L. Weller Roska, Scott Rajski, Paul R. Thompson

Research output: Contribution to journalArticlepeer-review

Abstract

Protein arginine methyltransferases (PRMTs) are (S)-adenosylmethionine (SAM)-dependent methyltransferases that catalyze the post-translational methylation of Arg residues in a variety of different proteins involved in transcriptional regulation and RNA splicing (e.g., histones H2A, H3, and H4). Herein, we describe the use of an N-mustard, 5'-(diaminobutyric acid)-N-iodoethyl-5'-deoxyadenosine ammonium hydrochloride (AAI), to generate a bisubstrate analogue inhibitor of PRMT1. Using the approach outlined in this communication, it should be possible to generate bisubstrate analogue-based inhibitors of PRMT isozymes that are potent and highly selective for a particular isozyme. The fact that PRMT1 catalyzes AAI transfer is also significant because with appropriate modifications (e.g., functionalization with pendant azido or alkyne functionalities) this compound could be used for proteomic applications to identify novel PRMT substrates.

Original languageAmerican English
JournalJournal of the American Chemical Society
Volume130
StatePublished - 2008

Keywords

  • Protein arginine methyltransferases
  • RNA splicing
  • Transcriptional regulation

DC Disciplines

  • Chemistry

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