Solid phase synthesis of rage ligands

RAGE (AGEs receptor) activity has been associated with pathological conditions characterized by persistent inflammation, such as diabetes mellitus cardiovascular complications, atherosclerosis, Alzheimer's and autoimmune diseases. Among AGEs, the major RAGE ligands are the protein adducts carboxy-methyl-lysine (CML) and carboxy-ethyl-lysine (CEL) that are known to bind the receptor only if they are incorporated into a peptide or a protein. Numerous studies related to AGEs or RAGE are reported, but there is a substantial lack of a solid phase synthesis protocol for the obtainment of CML and CEL peptides. In fact, most of the synthetic procedures for CML or CEL peptides use liquid-phase synthesis or the synthesis of the CML/CEL-amino acid in liquid phase followed by its inclusion by solid phase synthesis in the peptide sequence. (2-4) We report here a solid phase protocol for the direct carboxymethylation or carboxyethylation of peptides on solid phase, obtaining a streamlined process that gives these compounds in high yields.