Research in our group focuses on modulating protein-protein interactions through the use of small molecules and bio-inspired peptide scaffolds. By controlling such processes using synthetic molecules that we make in the laboratory, we seek to develop new chemical probes for understanding the underlying biology of protein-protein interactions in disease and ultimately novel therapeutics. Within this interdisciplinary research program, we combine techniques in organic synthesis, biophysics, biochemistry and molecular biology to investigate the folding/misfolding and disease pathways of intrinsically disordered proteins (IDPs). Our research program exploits the bio-orthogonality and the hypersensitivity of fluorine as an NMR probe for exploring important protein-protein interactions of IDPs. Our ultimate goal is to study these proteins in their native environment – whole cells – using 19F NMR. This research is complemented with established spectroscopic techniques, organic synthesis of chemical probes, and new peptide-based strategies for pre-organization and cellular delivery for studying challenging IDPs under physiological conditions.
