Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, 55455, USA.
Institute for Translational Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA.
Chem Commun (Camb). 2022 Jan 18;58(6):855-858. doi: 10.1039/d1cc06651j.
Protein glycation is a disease associated, non-enzymatic, posttranslational modification generated by endogenous dicarbonyl metabolites. Currently, there is a lack of chemical tools capable of studying protein adducts caused by this class of reactive species. Here, we report a chemical biology platform, termed T-DiP (targetable-dicarbonyl precursor), that releases a physiologically relevant dose of bio-orthogonally functionalized dicarbonyl probe upon irradiation with 365 nm light. This approach enables protein glycation to be controlled with spatiotemporal precision within live cells and expands the chemical toolbox needed to elucidate the roles of glycated proteins across various pathologies.
蛋白质糖基化是一种与疾病相关的、非酶促的、翻译后修饰，由内源性二羰基代谢物产生。目前，缺乏能够研究此类反应性物质引起的蛋白质加合物的化学工具。在这里，我们报告了一种化学生物学平台，称为 T-DiP（靶向二羰基前体），它在 365nm 光照射下释放出生理相关剂量的生物正交功能化二羰基探针。这种方法可以在活细胞内精确地控制蛋白质糖基化，并扩展了阐明各种病理中糖化蛋白作用所需的化学工具包。
