William C. Pomerantz '02, University of Minnesota is Chemistry Dept. Seminar guest speaker on Tuesday, October 14th at 4:15 p.m. in CNS 333. Prof. Pomerantz presentation topic will be focused on; “Aromatic Amino Acids: Privileged Side-Chains For Protein-Protein Interaction Inhibitor Discovery”.
We describe our recent results developing spectroscopic drug screening methods using 19F NMR to discover organic molecules for modulating gene regulation of transcription factors. Given that transcription factors represent a major class of potential drug targets, our proposed 19F NMR approach to study protein-ligand interactions may increase the repertoire of new targets and thereby open up new avenues for drug/probe discovery.Here we lay the framework for our ligand discovery goals using fluorinated transcription factor protein-protein interaction domains, showing high incorporation (>90%) of all three fluorinated aromatic amino acids into two different proteins. We determine optimal labeling for developing a sensitive and structure-based method for ligand discovery. We characterize the binding footprints of known ligands and demonstrate our approach in a 500 compound small molecule fragment screen. Finally, using circular dichroism, fluorescence polarization, and x-ray crystallography, we demonstrate the non-perturbing nature of fluorine when placed on aromatic amino acids at protein-protein interaction interfaces.
Individuals with disabilities requiring accommodations should contact Maria Russell at mrussell@ithaca.edu or (607) 274-3282. We ask that requests for accommodations be made as soon as possible
https://www.ithaca.edu/intercom/article.php/20141013081957573