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.
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.
Ziegler
Thomas
T
Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany. thomas.ziegler@uni-tuebingen.de
Schips
Carsten
C
D000596:Amino Acids / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D006020:Glycopeptides / Q000138:chemical synthesis*; D006031:Glycosylation; D019151:Peptide Library
D000596:Amino Acids; D006020:Glycopeptides; D019151:Peptide Library