Cysteine Arylation to Engineer Peptides and Proteins

During his talk, Prof. Pentelute will report a robust bioconjugation method using cysteine arylation. This chemistry enables site-specific conjugation at cysteine residues within peptides, proteins, and antibodies. His two developed approaches use either perfluoroaryl-cysteine SNAr chemistry or organometallic palladium reagents. This work lead to the discovery of a self-labeling four-residue sequence that enables regioselective conjugation at only one cysteine residue within an intact antibody containing natural amino acids. Recently, his lab discovered a new approach for the native conjugation of complex natural products such as vancomycin onto peptides and proteins without the introduction of linkers or chemical handles.

Some relevant publications:

• Cohen, D.T.,*  Zhang, C.,* Pentelute, B.L.*, Buchwald, S.L.*, (2015) An Umpolung Approach for the Chemoselective Arylation of Selenocysteine in Unprotected Peptides, Journal of the American Chemical Society, 137(31), 9784-7 (*Co-corresponding authors and first authors)
• Vinogradova, E.V.*, Zhang, C.*, Spokoyny, A. M., Pentelute, B.L.*, Buchwald, S.L.,* (2015). Organometallic palladium reagents for cysteine bioconjugation. Nature, 526(7575), 687-691 (*Co-corresponding authors and first authors)
• Zhang, C., Welborn, M., Zhu, T., Santos, M., Yang, N., Van Voorhis, T., Pentelute, B.L., (2016). π-Clamp mediated cysteine conjugation. Nature Chemistry, 8(2), 120-8