Investigating N-mustard-based analogs of SAM as probes of biological methylation

有了这个奖项，化学部的生命过程化学计划正在资助维克森林大学的林赛康斯托克博士开发和研究一套新的生化工具作为通用探针来识别生物甲基化位点。具体地，细胞甲基转移酶促进具有叠氮化物和炔官能团的S-腺苷-L-甲硫氨酸的合成的含N-芥子气类似物转移到其相应的生物分子，如DNA和蛋白质。一旦掺入，这些功能可以通过具有荧光团和亲和标签的化学选择性连接化学进行修饰，以允许在复杂混合物中可视化和从复杂混合物中分离，从而产生可以容易地表征的产物。DNA和蛋白质甲基转移酶属于一类独特的酶，已被充分证明在关键细胞功能中发挥作用，包括代谢和细胞生长。虽然已经确定DNA和蛋白质甲基转移酶活性指导各种各样的细胞过程，但该项目正在开发的生物化学工具旨在识别生物甲基化的特定位点，最终目标是更好地理解细胞过程中的甲基化。这项研究将允许本科生和研究生与生物化学和细胞生物学专家合作，在化学和生物学之间的接口从事奖学金。

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.