Martin Group: Medicinal Chemistry & Chemical Biology

Address

Keywords

Methytransferase enzymes, synthetic chemistry, peptides, inhibitors, medicinal chemistry

Models

Synthetic organic chemistry, SPPS, medicinal chemistry, biochemical assays

Techniques

NMR, analytical- and preparative-scale RP-HPLC, MS analysis

Collaborations outside COST

Adam Frankel (UBC, Canada), Richard Parsons (Kings College London), Monica Emanuelli (Università Politecnica Delle Marche, Italy), Jean Cavarelli (IGBMC, France)

Short description of ongoing research projects

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).

Publications

1. Koopmans, T.; Wood, T.M.; ‘t Hart, P.; Kleijn, L.H.K.; Hendrickx, A.P.A.; Willems, R.J.L.; Breukink, E.; *Martin, N.I. J. Am. Chem. Soc., 2015, 137, 9382–9389.
2. Oude Blenke, E.; Klaasse, G.; Merten, H.; Plückthun, A.; Mastrobattista, E.; *Martin, N.I. J. Control. Release, 2015, 202, 14-20.
3. van Haren, M.; Quarles van Ufford, L.; Moret, E.E.; *Martin, N.I. Org. Biomol. Chem., 2015, 13, 549-560.
4. Thomas, D.; Koopmans, T.; Lakowski, T.M.; Kreinin, H.; Bui, J.M.; Vhuiyan, M.I.; *Martin, N.I., *Frankel, A. ChemBioChem, 2014, 15, 1607-1613.
5. Mooney, C.A.; Johnson, S.A.; ‘t Hart, P.; Quarles van Ufford, L.; de Haan, C.A.M.; Moret, E.E.; *Martin, N.I., J. Med. Chem., 2014, 57, 3154–3160.

Other activities of potential interest to others

Co-founder of startup biotech company Synamp Pharmaceuticals BV (http://synamp-pharma.com/).