Solid-phase synthesis of glucose-derived Amadori peptides

✍ Scribed by Andrej Frolov; David Singer; Ralf Hoffmann

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 276 KB
• Volume: 13
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.901

✦ Synopsis

Abstract

Nonenzymatic glycosylation or glycation of amino groups in peptides and proteins by D‐glucose is a universal reaction with important implications for the pathogenesis of many diseases including diabetes mellitus. Here a general approach is reported to synthesize site specifically glucose‐derived N‐glycated peptides. Therefore, model peptides H‐AKASASFL‐NH~2~, H‐AKASADFL‐NH~2~, H‐ASKASKFL‐NH~2~, and H‐AKDSASFL‐NH~2~ were synthesized on solid phase by Fmoc chemistry using Fmoc‐Lys(4‐methyltrityl)‐OH in positions 2 or 3 to be glycated. After completion of the synthesis, the acid labile 4‐methyltrityl‐group was cleaved with 1% TFA in DCM and the free amino groups were glycated by the Lobry de Bruyn reaction using 2,3:4,5‐di‐O‐isopropylidene‐aldehydo‐β‐D‐arabino‐hexos‐2‐ulo‐2,6‐pyranose on solid phase. After TFA treatment, the crude peptides were obtained in high yields and purities above 80%. Minor by‐products were well separated on reversed‐phase HPLC. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.