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

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

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)6158-6164
    Number of pages6
    JournalChemical Science
    Volume6
    Issue number11
    DOIs
    Publication statusPublished - 24 Jul 2015

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology

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