Development of chemical tools for the study and manipulation of biological systems.
Dana Farber Cancer Institute
Longwood Center 3214
450 Brookline Ave.
Boston, MA 02215
Lab Size: Between 5 and 10
Research in our lab takes a bottom-up approach to tackling molecular challenges in cancer biology. Basic chemical research – development of new reactions, exploration of novel synthetic strategies, discovery of new molecular reactivity, and synthesis of complex molecular architectures – fuels our drive to access useful compounds for the study and manipulation of biological systems. Our biological interests lie in the areas of tumor hypoxia, gram-negative pathogens, and protein-protein interactions.
Exploiting functional specificity: Drug discovery efforts predominantly target human pathologies by exploiting the structural complementarity between small molecules and the binding pockets of dysregulated proteins. We envision the design of new therapeutic and imaging agents that are responsive to the unique chemical microenvironments of diseased cells and pathogens. Such a strategy, enabled by fundamental chemical developments and access to new compositions of matter, will facilitate both the discovery of new pharmaceutical agents and the repurposing of old drugs for new diseases.
Probing macromolecular interactions: Our lab will take a chemical approach to targeting macromolecular interactions. While much of life’s processes are governed by protein-protein and protein-nucleic acid interactions, only a small fraction of these can be manipulated using small molecules. The identification of small organic molecules capable of binding flat interfacial surfaces is incredibly difficult, but we envision that the development of a high throughput discovery platform employing a set of privileged molecular scaffolds will enable us to target some of these traditionally undruggable targets.
Natural product synthesis: Designing potent bioactive small molecules with drug-like properties de novo is undoubtedly challenging. Natural products have long been a source of inspiration for the development of new therapeutic agents. A majority of pharmaceutical agents that have gained clinical approval over the past several decades derive from naturally occurring metabolites. We aim to synthesize potent bioactive natural products as the first step in elucidating their biology, creating structural derivatives, and developing new tool compounds and therapeutic agents.
Kim, J.; Bertozzi, C. R. Angew. Chem. Int. Ed. 2015, 54, 15777–15781. “Bioorthogonal Reaction of N-oxide and Boron Reagents.”
Coste, A.; Kim, J.; Adams, T. C.; Movassaghi, M. Chem. Sci. 2013, 4, 3191–3197. “Concise Total Synthesis of (+)-Bionectins A and C.”
Kim, J.; Movassaghi, M. J. Am. Chem. Soc. 2011, 133, 14940–14943. “Concise Total Synthesis and Stereochemical Revision of (+)-Naseseazines A and B: Regioselective Arylative Dimerization of Diketopiperazine Alkaloids.”
Kim, J.; Movassaghi, M. J. Am. Chem. Soc. 2010, 132, 14376–14378. “General Approach to Epipolythiodiketopiperazine Alkaloids: Total Synthesis of (+)-Chaetocins A and C and (+)-12,12'-Dideoxychetracin A.”
Kim, J.; Ashenhurst, J. A.; Movassaghi, M. Science 2009, 324, 238–241. “Total Synthesis of (+)-11,11'-Dideoxyverticillin A.”