Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer

Hansen, Steen U.; Miller, Gavin J.; Cliff, Matthew J.; Jayson, Gordon C.; Gardiner, John M.

Abstract

The chemical synthesis of long oligosaccharides remains a major challenge. In particular, the synthesis of glycosaminoglycan (GAG) oligosaccharides belonging to the heparin and heparan sulfate (H/HS) family has been a high profile target, particularly with respect to the longer heparanome. Herein we describe a synthesis of the longest heparin-related oligosaccharide to date and concurrently provide an entry to the longest synthetic oligosaccharides of any type yet reported. Specifically, the iterative construction of a series of [4]n-mer heparin-backbone oligosaccharides ranging from 16-mer through to the 40-mer in length is described. This demonstrates for the first time the viability of generating long sequence heparanoids by chemical synthesis, via practical solution-phase synthesis. Pure-Shift HSQC NMR provides a dramatic improvement in anomeric signal resolution, allowing full resolution of all 12 anomeric protons and extrapolation to support anomeric integrity of the longer species. A chemically pure 6-O-desfulfated GlcNS-IdoAS icosasaccharide (20-mer) represents the longest pure synthetic heparin-like oligosaccharide.

Citation

Hansen, S. U., Miller, G. J., Cliff, M. J., Jayson, G. C., & Gardiner, J. M. (2015). Making the longest sugars: a chemical synthesis of heparin-related [4](n) oligosaccharides from 16-mer to 40-mer. Chemical Science, 6(11), 6158 - 6164. https://doi.org/10.1039/C5SC02091C

• Journal Article Type: Article
• Acceptance Date: Jul 23, 2015
• Publication Date: Jul 24, 2015
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 6
• Issue: 11
• Pages: 6158 - 6164
• DOI: https://doi.org/10.1039/C5SC02091C
• Publisher URL: https://doi.org/10.1039/c5sc02091c