Abstract
Methylglyoxal is a highly reactive metabolite that is formed spontaneously in the glycolytic pathway. The side chains of various amino acid residues react with methylglyoxal to form advanced-glycation end products (AGEs). This enzyme-independent process introduces post-translational modifications onto the proteins and it is long thought that the resulting AGEs primarily inhibit proteins. More recent studies have shown that these AGEs can act in signaling and feedback loops and that a large number of proteins react reversibly with methylglyoxal. These findings lead to a renewed interest in methylglyoxal-induced AGEs and lead to the development of novel tools and methodologies that can be used to identify the modified proteins. Many of studies are nowadays still performed by adding methylglyoxal exogenously, often in a high concentration, despite the high reactivity of methylglyoxal. Herein, new photocaged-methylglyoxal derivatives are reported that allow the direct release of methylglyoxal in the sample of interest by irradiating the photocaged probe with UV light. It is shown that this labeling approach is more efficient. A far larger number of proteins are labeled with the photocaged probes than with the chemically activated probes. The here reported approach should allow studying in situ glycation under physiological more relevant conditions.