Methytransferase enzymes, synthetic chemistry, peptides, inhibitors, medicinal chemistry
Synthetic organic chemistry, SPPS, medicinal chemistry, biochemical assays
NMR, analytical- and preparative-scale RP-HPLC, MS analysis
Adam Frankel (UBC, Canada), Richard Parsons (Kings College London), Monica Emanuelli (Università Politecnica Delle Marche, Italy), Jean Cavarelli (IGBMC, France)
A growing body of evidence now implicates dysregulated PRMT activity in a number of diseases including various forms of cancer. The development of PRMT inhibitors may therefore hold potential as a means of developing new therapeutics. To this end my group has recently described the preparation of a number of peptide-based PRMT inhibitors (ChemBioChem. 2014, MedChemComm. 2012, ChemBioChem. 2011, ACS Chem. Biol. 2010). In these studies, known PRMT substrate peptides were transformed into inhibitors by introduction of various guanidine substituents using synthetic methodology developed in house (J. Org. Chem. 2008). More recently we have also explored non-peptide, small molecule PRMT inhibitors designed to simultaneously occupy both the SAM and arginine binding sites. This work has led to the discovery of a series of new potent, and isozyme-selective, PRMT inhibitors with IC50 values in the nanomolar range (Org. Biomol. Chem. 2015).
Co-founder of startup biotech company Synamp Pharmaceuticals BV (http://synamp-pharma.com/).