Bioorganic Chemistry/Chemical Biology
- Email: email@example.com
- Office: JMH 638
- Lab: JMH 633/640
- Assistant Professor at Fordham University
- NIH NRSA Postdoctoral Fellow at New York University
- Ph.D. in Molecular Biophysics and Biochemistry from Yale University
- B.Sc. in Biochemistry from Rutgers University
Research in my group aims to synthesize and evaluate molecules that imitate interacting protein surfaces to investigate the sequence-structure-function relationship of protein-protein interactions involved in human health and disease. Such molecules have utility as both probes for understanding essential biological processes and for innovation in drug development.
Protein-protein interactions (PPIs) are fundamental to biological processes that allow cells to communicate and adapt to stress. The functional groups and their relative orientation on a protein’s surface ultimately determine how strongly and specifically a protein binds to its partner protein(s) through the formation of many weak non-covalent interactions. Some functional groups contribute more strongly to complex formation than others and are thus considered "hot spots."
A central hypothesis in my research is that molecules that reproduce the hot spots of a protein surface can competitively modulate its PPI functions. This hypothesis has been explored previously for many of the >500,000 PPIs, specifically those that are dominated by regular secondary and tertiary structures, including α-helices, β-sheets, and coiled coils. However, the other half of the protein-protein interactome is mediated by non-regular “loop” structures and remains poorly understood.
At the interface between chemistry and biology, research in my lab seeks to develop and apply synthetic approaches to examine the roles of loops in PPIs. Specific research areas include 1) sequence- independent strategies to stabilize specific loop structures and 2) control of loop structure to drive preferential binding to specific protein targets. Ultimately, the synthetic strategies and molecules will provide important insights into fundamental biological processes associated with human health and disease.
Sawyer, N., Arora, P.S. Hydrogen Bond Surrogate Stabilization of β-Hairpins. ACS Chem. Biol., 2018, 13, 2027.
Sawyer, N., Gassaway, B.M., Haimovich, A.D., Isaacs, F.J., Rinehart, J., Regan, L. Designed phosphoprotein recognition in Escherichia coli. ACS Chem. Biol., 2014, 9, 2502.
Chen, J., Sawyer, N., Regan, L. Protein-protein interactions: general trends in the relationship between binding affinity and interfacial buried surface area. Protein Sci., 2013, 22, 510.