A Chemoproteomic Approach to Study Advanced Glycation End-Products

Protein glycation is a non-enzymatic process in which an arginine or lysine residue of a protein reacts irreversibly with a carbohydrate or a dicarbonyl compound. The process is commonly observed in ageing related disorders and the resulting advanced glycation end-products (AGEs) represent potential biomarkers for these diseases. The most potent glycating agent is glyoxal. Chemical tools that enable the discovery of glyoxal modification sites under physiological conditions may lead to novel biomarkers. Several chemical probes have been developed for this purpose, however they have many limitations due to highly reactive nature of the dicarbonyl structure.To address these limitations, we developed a novel chemical probe which is activated by light and releases glyoxal species directly into the biological sample of interest. In the presented study we compare currently used probes with photoactivated probe and show the potential and utility of this novel chemical tool to analyse biological sample and study the function and effect of advanced glycation end products. We show the application of the new probe to modify arginine in bovine serum albumin as a model protein and to identify advanced glycation end products in A549 cells.