title: Modular synthesis of heparin-related tetra-, hexa- and octasaccharides with differential o-6 protections: programming for regiodefined 6-o-modifications.
abstract: Heparin and heparan sulphate (H/HS) are important members of the glycosaminoglycan family of sugars that regulate a substantial number of biological processes. Such biological promiscuity is underpinned by hetereogeneity in their molecular structure. The degree of O-sulfation, particularly at the 6-position of constituent D-GlcN units, is believed to play a role in modulating the effects of such sequences. Synthetic chemistry is essential to be able to extend the diversity of HS-like fragments with defined molecular structure, and particularly to deconvolute the biological significance of modifications at O6. Here we report a synthetic approach to a small matrix of protected heparin-type oligosaccharides, containing orthogonal D-GlcN O-6 protecting groups at programmed positions along the chain, facilitating access towards programmed modifications at specific sites, relevant to sulfation or future mimetics.
authors: Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK.
authors: Marek
authors: M
authors: Baráth
authors: Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK.
authors: Steen U
authors: SU
authors: Hansen
authors: Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK.
authors: Charlotte E
authors: CE
authors: Dalton
authors: Institute of Cancer Sciences, Christie Hospital and University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
authors: Gordon C
authors: GC
authors: Jayson
authors: Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK.
authors: Gavin J
authors: GJ
authors: Miller
authors: Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK.
authors: John M
authors: JM
authors: Gardiner
mesh_terms: D032701:Biomimetics; D006025:Glycosaminoglycans / Q000138:chemical synthesis* / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006497:Heparan Sulfate / Q000737:chemistry; D007067:Iduronic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D006025:Glycosaminoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007067:Iduronic Acid; D009844:Oligosaccharides