With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Lindsay Comstock from Wake Forest University to develop and investigate a novel set of biochemical tools as universal probes to identify biological methylation sites. Specifically, cellular methyltransferases facilitate transfer of synthetic N-mustard-containing analogs of S-adenosyl-L-methionine bearing azide and alkyne functionalities to their corresponding biomolecules, such as DNA and protein. Once incorporated, these functionalities can be modified through chemoselective ligation chemistries with fluorophores and affinity tags to permit both visualization in, and isolation from, complex mixtures, yielding products that can be easily characterized.
DNA and protein methyltransferases belong to a unique class of enzymes which have been well documented to play a role in key cellular functions, including metabolism and cell growth. While it has been established that DNA and protein methyltransferase activities direct a wide variety of cellular processes, the biochemical tools being developed in this project are designed to identify specific sites of biological methylation, with the ultimate goal of better understanding of methylation in cellular processes. This research will allow for undergraduate and graduate students to engage in scholarship at the interface between chemistry and biology, in collaboration with experts in biochemistry and cell biology.
