Complex biological systems regulate the activity states of proteins by numerous posttranslational modifications. Utilizing an interdisciplinary approach that merges synthetic chemistry, biochemistry, and protein mass spectrometry, our group seeks to interrogate the role of these posttranslational protein modifications in modulating protein activity in physiology and disease. We are particularly interested in the functional significance of protein oxidation and glycosylation and seek to develop novel chemical proteomic technologies for profiling these protein modifications. We will concentrate on three specific areas of research: 1) Development of novel chemical probes to identify protein targets for antibiotic drug development; 2) Elucidation of the role of protein glycosylation in bacterial pathogenesis; and 3) Investigation of the extent and physiological effect of protein oxidation events associated with aging.


Representative Key Publications:

Weerapana, E., Wang, C., Simon, G.M., Richter, F., Khare, S., Dillon M.B.D., Bachovchin, D.A., Mowen, K., Baker, D., and Cravatt, B.F. Quantitative reactivity profiling predicts functional cysteines in proteomes. Nature, 2010, in press.

Weerapana, E., Simon, G. M., Cravatt, B. F. Disparate proteome reactivity profiles of carbon electrophiles. Nat. Chem. Biol. 2008, 4, 405-7.

Weerapana, E., Speers, A. E. and Cravatt, B. F. Tandem orthogonal proteolysis-activity-based protein profiling (TOP-ABPP) – a general method for mapping sites of probe modification in proteomes. Nat. Protocols., 2007, 2, 1414-25.

Weerapana, E., Glover, K. J. and Imperiali, B. Investigating bacterial N-linked glycosylation: synthesis and glycosyl acceptor activity of the undecaprenyl pyrophosphate-linked bacillosamine. J. Am. Chem. Soc. 2005, 127, 13766-7.