In situ generation of a bisubstrate analogue for protein arginine methyltransferase 1

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Deoxyadenosines; Enzyme Inhibitors; Isoenzymes; Kinetics; Peptides; Protein-Arginine N-Methyltransferases; inhibitors; Repressor Proteins; Substrate Specificity


Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics


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.

DOI of Published Version



J Am Chem Soc. 2008 Apr 9;130(14):4574-5. doi: 10.1021/ja077104v. Link to article on publisher's site. Epub 2008 Mar 14.

Journal/Book/Conference Title

Journal of the American Chemical Society


At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed