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 beta-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.