William C. Pomerantz, PhD

Pomerantz Lab Group

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 study the role epigenetic regulatory proteins play in disease.Our current focus is on developing chemical probes for modulating protein-protein interactions of bromodomain-containing proteins, Brd4 and BPTF.

Our research program exploits the bio-orthogonality and the hypersensitivity of fluorine as an NMR probe for providing structural inforatmion of protein interfaces and for use as a tool for small molecule screening in the area of fragment-based drug discovery. As a new direction, we have also begun to use highly fluorinated molecules for design of new imaging agents for ¹⁹F MRI. Beyond 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 epigenetic proteins under physiological conditions.

• F32 NIH postdoctoral Research Fellow
• 2016 Chemical Biology Rising Star Award
• McKnight Land Grant Assistant Professor

• American Chemical Society
• American Peptide Society

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.

PubMed Bibliography

1.Kirberger, S. E.; Ycas, P. D.; Johnson, J. A.; Chen, C.; Ciccone, M. F.; Woo, R. W. L.; Urick, A. K.; Zahid, H.; Shi, K.; Aihara, H.; McAllister, S. D.; Kashani-Sabet, M.; Shi, J.; Dickson, A.; Dos Santos, C. O.; Pomerantz, W. C. K. Selectivity, ligand deconstruction, and cellular activity analysis of a BPTF bromodomain inhibitor. Org. Biomol. Chem. 2019, 17, 2020-2027.

2.Paulson, C. N.; Guan, X.; Ayoub, A. M.; Chan, A.; Karim, R. M.; Pomerantz, W. C. K.; Schonbrunn, E.; Georg, G. I.; Hawkinson, J. E. Design, synthesis, and characterization of a fluorescence polarization pan-BET bromodomain probe. ACS Med. Chem. Lett. 2018, 9, 1223-1229.

3.Divakaran, A.; Talluri, S. K.; Ayoub, A. M.; Mishra, N. K.; Cui, H.; Widen, J. C.; Berndt, N.; Zhu, J. Y.; Carlson, A. S.; Topczewski, J. J.; Schonbrunn, E. K.; Harki, D. A.; Pomerantz, W. C. K. Molecular basis for the N-terminal bromodomain-and-extra-terminal-family selectivity of a dual kinase-bromodomain inhibitor. J. Med. Chem. 2018, 61, 9316-9334.

4.Gee, C. T.; Arntson, K. E.; Koleski, E. J.; Staebell, R. L.; Pomerantz, W. C. K. Dual Labeling of the CBP/p300 KIX domain for (19) F NMR leads to identification of a new small-molecule binding site. ChemBioChem 2018, 19, 963-969.

5.Perell, G. T.; Mishra, N. K.; Sudhamalla, B.; Ycas, P. D.; Islam, K.; Pomerantz, W. C. K. Specific acetylation patterns of H2A.Z form transient interactions with the BPTF bromodomain. Biochemistry 2017, 56, 4607-4615.