An efficient Mitsunobu protocol for the one-pot synthesis of S-glycosyl amino-acid building blocks and their use in combinatorial spot synthesis of glycopeptide libraries

Abstract

Complex glycosylation patterns on cell surfaces are involved in many fundamental biological processes like specific cell–cell interactions and signal transduction. Furthermore, the glycon part of glycopeptides and glycosylated proteins play a crucial role in numerous ligand–receptor interactions of biological significance. However, the distinct function of complex carbohydrate structures associated with cell surfaces and proteins is still only poorly understood at a molecular level with regard to specific carbohydrate–protein interaction. Here, we present an efficient Mitsunobu protocol for the convenient chemical one-pot preparation of S-glycosyl amino-acid building blocks suitable for automated combinatorial syntheses of highly glycosylated β-peptides, which, in turn, can serve as potential mimics for complex oligosaccharides or for studying carbohydrate–protein interactions. The protocol also describes the use of the S-glycosyl amino-acid building blocks for combinatorial spot syntheses of glycopeptide libraries and can be used for the construction of other combinatorial peptide libraries as well. This is a procedure that can be completed in approximately 7 days.