Targeting protein arginine N-methyltransferases with peptide-based inhibitors: opportunities and challenges

Recently peptide-based inhibitors have been used to selectively inhibit a family of epigenetic enzymes called protein arginine N-methyltransferases (PRMTs), which has been implicated in different physiological processes and human diseases, such as heart disease and cancer. The diverse efforts to tease out subtle structural differences among PRMT enzymes in order to generate selective inhibitors as well as existing challenges in the field will be examined. The acquisition of PRMT substrate sequence preferences and structural information obtained from small-molecule inhibitors have helped in developing different peptide-based inhibitors that show great promise not only as inhibitors, but also as molecular probes to characterize PRMTs.