Solid‐phase synthesis of glucose‐derived Amadori peptides

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.