Assistant Professor, NC State University
New Strategies for Ketoxime Peptide Ligations
Chemoselective reactions that occur under mild conditions are required to synthesize and probe biomolecules in aqueous settings. To that end, ligation of aminooxy groups with a-oxo-aldehydes or ketones have been widely pursued; however, addition of superstoichiometric amounts of aniline are typically required to construct oxime bonds at neutral pH via formation of an aniline Schiff-base intermediate. Moreover, while starting from ketone substrates instead of aldehydes would allow substitution at the site of ligation, synthetic challenges to access ketone derivatives from common amino acid building blocks and their slow reactivity in condensation reactions have precluded the widespread use of ketoxime peptide ligations. Here, we expand the utility of oxime ligation reactions by providing direct access to reactive a-imino amide intermediates from a site-selective, aerobic oxidation of N-aryl peptides. We demonstrate that the reactivity of N-aryl peptides can be modulated by the electronics of the aryl ring, and that various substitution at the a-carbon can be introduced to afford ketoxime peptide bonds in high yield
Caroline Proulx obtained her Hon. B.Sc. from the University of Ottawa in Biopharmaceutical Sciences (Medicinal Chemistry) in 2007, working under the supervision of Prof. Robert N. Ben. In 2012, she obtained her Ph.D. in Chemistry from the Université de Montréal under the guidance of Prof. William D. Lubell, where she worked on the development of methodologies for the combinatorial synthesis of azapeptides. From 2012-2016 she was an NSERC postdoctoral fellow at the Molecular Foundry, Lawrence Berkeley National Laboratory, working with Dr. Ronald N. Zuckermann on peptoid synthesis and self-assembly. She joined the faculty at North Carolina State University in July 2016 as an Assistant Professor, where she develops new tools and synthetic methods to access peptide and protein mimics for medicinal chemistry and chemical biology applications.