Chemoselective synthesis of peptides containing major advanced glycation end-products of lysine and arginine.

Useful methodologies have been developed, enabling the straightforward synthesis of peptides containing N(epsilon)-(carboxymethyl)-L-lysine (CML) and N(epsilon)-(carboxyethyl)-L-lysine (CEL), the major glycation end-products of lysine. These lysine derivatives were successfully incorporated into growing peptide chains via standard Fmoc/Ot-Bu peptide synthesis procedures. For the synthesis of peptides containing major glycation end-products of arginine, synthetic routes have been developed enabling the transformation of ornithine residues in peptides into the well-known arginine-derived advanced glycation end-products (AGEs) Glarg, carboxymethyl-L-arginine (CMA), MG-H1, MG-H2, MG-H3, and carboxyethyl-L-arginine (CEA), respectively, by means of special modifying agents. Furthermore, it was shown that Glarg-containing peptides become quantitatively hydrolyzed into CMA-peptides under physiologic conditions. A similar reaction was observed in case of a MG-H3-peptide, which turned into a CEA-peptide under these conditions.