Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases

Prototype inhibitors of protein arginine methyltransferases (PRMTs) have been constructed by attaching guanidine functionality via a variable linker to non-reactive amine analogues of the cellular co-factor (S)-adenosyl methionine (AdoMet). Potent inhibition of PRMT1 (IC50 of similar to 3-6 mu M) combined with weak inhibition of the lysine methyltransferase SET7 (similar to 50% of activity at 100 mu M) was observed for two such compounds. (C) 2010 Elsevier Ltd. All rights reserved.