Synthesis of an Alkynyl Methylglyoxal Probe to Investigate Nonenzymatic Histone Glycation.

Methylglyoxal (MGO) is a reactive dicarbonyl metabolite that modifies histones in vivo and induces changes in chromatin structure and function. Here we report the synthesis and application of a chemical probe for investigating MGO-glycation. A two-step synthesis of a Cu-click compatible alkynyl oxoaldehyde probe (AlkMGO) via sequential Dess-Martin and Riley oxidations is presented. This synthesis elevates the accessibility and utility of an important tool for tracking, enriching, and studying MGO-glycation to aid in understanding its underlying biochemical functions.