Mark Tye

Background

About Mark Tye

I am a passionate medicinal chemist working on the RAS/MAPK pathway. During my Ph.D. in Chemical Biology at Harvard University, I worked in the Mazitschek group on an integrated chemogenomic approach exploring and exploiting prolyl-tRNA synthetase (ProRS) as target for next-generation malaria and cancer therapies. As part of this, I designed a diverse set of high affinity inhibitors, including the first triple-site ligands for any aminoacyl-tRNA synthetase (aaRS) enzyme that simultaneously engage all three substrate-binding pockets. Guided by the SAR data from my inhibitors and representative co-crystal structures, I overcame existing technology limitations by developing the first Time-Resolved Förster Resonance Energy Transfer (TR-FRET) based aaRS ligand displacement assay platform for direct biochemical characterization of ProRS ligands, including substrate competitiveness and binding kinetics. During my undergraduate studies, I worked in the Francis group at U.C. Berkeley developing and implementing new bioconjugation chemistry for targeted drug delivery of photodynamic therapy agents using a modified MS2 virus capsid in order to treat phytopathogenic fungi.