Our group focuses on synthesis and synthetic methodology to tackle problems of relevance to medicinal chemistry and biotechnology. Essentially, the three current active projects are:
- syntheses, mediated by organometallic catalysts, of privileged chirons found in natural products;
- syntheses of dipeptide mimics;
- use of a special method to construct combinatorial libraries of molecules designed to disrupt or mimic protein-protein interactions; and,
- syntheses of fluorescent through-bond-energy-transfer cassettes to facilitate observation of protein-protein interactions in cells.
How do such diverse projects fit together to form an integrated program? The privileged chirons that we prepare will be assembled into chimeric natural product analogs, "Frankenstein molecules", with desirable molecular characteristics for binding to proteins. These will be incorporated into bivalent molecules, often in combination with peptidomimetics; these are designed to mimic dipeptide fragments commonly found in hot-spots at protein-protein interactions. These bivalent molecules are labeled with a fluorescent dye. The dye has two functions: (i) to facilitate screening for molecules that bind to proteins; and, (ii) to track the distribution of the bivalent molecules on or inside cells.
Water-soluble Through-bond Energy Transfer Cassettes in Intracellular Imaging, Bandichhor, R.: Petrescu, A. D.: Vespa, A.; Kier, A. B.; Schroeder, F.; Burgess, K.; J. Am. Chem. Soc., 2006, 128, 10688.
Heterovalent Selectivity and The Combinatorial Advantage, Burgess, K.; Reyes, S. J.; Chem. Soc. Rev., 2006, 35, 416-23.
Ring Closure to β-Turn Mimics via Copper Catalyzed Azide/Alkyne Cycloadditions, Li, Y,; Burgess, K.; J. Org. Chem., 2006, 70, 9595-98.
Mechanistic Insights into Iridium-Catalyzed Asymmetric Hydrogenations of Dienes, Cui, X.; Fan, Y.; Hall, M. B.; Burgess, K., Chem. Eur. J., 2005, 11, 6859-68.