Concise Synthesis of Advanced Glycation Endproduct Derived from Arginine for Use in Solid-Phase Peptide Synthesis

Advanced glycation end products (AGEs) contribute to Diabetes and neurodegenerative diseases like Alzheimer’s disease by structurally diverse class of post-translational protein modifications prevalent but the mechanisms involved are not clear. Targeting AGEs has potential therapeutic implication. This protein glycation is produced through nonenzymatic reactions of arginine or lysine with glucose-derived alpha-dicarbonyl compounds. Glyoxal—a two carbon dialdehyde—is the smallest of this class and generates carboxymethyllysine (CML) from lysine, and Glarg with arginine. While CML modifications in proteins are frequently identified, observations of Glarg are relatively scarce as the imidazolone ring readily hydrolyzes to carboxymethylarginine (CMA) under harsher conditions. To better understand the impact of Glarg modifications on Alzheimer’s disease, we elucidate the mechanism of synthesizing the AGEs Glarg and protein with well-defined AGEs. The result indicated that the synthesized AGEs, Glarg hydrolyzed to CMA. We envision that this research will help provide new insights into the structural and functional impact of these protein modifications.