Expedient Synthesis of Peptides Containing Nε-Carboxymethyllysine

• Published in: Synlett 2014-08, Vol.25 (13), p.1835-1838
• Main Authors: Kamalov, Meder, Yang, Sunghyun, Harris, Paul W. R., Cooper, Garth J. S., Brimble, Margaret A.
• Format: Article
• Language: English
• Subjects: letter
• ISSN: 0936-5214; 1437-2096
• DOI: 10.1055/s-0033-1378305

Abstract Accumulation of advanced glycation endproducts ­(AGEs) is responsible for the development and progress of diabetes- and age-related complications. Synthesis of specific chemical probes is key for the detailed understanding of biochemical properties of AGEs and their precise roles in the progression of disease. We herein report the expedient synthesis of such probes in the form of peptides site-specifically glycated by the major lysyl AGE, N ε -carboxymethyllysine (CML). The facile and economical incorporation of CML into peptide sequences by using the nosyl group has been achieved in a single step on resin. This new method is a substantial improvement over the existing syntheses of CML-containing peptides in that it does not require the use of expensive reagents or elaborate purification techniques. The impact of CML on the proteolytic stability of the host peptide has been investigated using trypsin digest studies.