Modular Synthesis of Heparin-Related Tetra-, Hexa- and Octasaccharides with Differential O-6 Protections: Programming for Regiodefined 6-O-Modifications

Molecules

Marek Baráth²  Steen U. Hansen²  Charlotte E. Dalton²  Gordon C. Jayson¹  Gavin J. Miller²  John M. Gardiner² 

[1] Institute of Cancer Sciences, Christie Hospital and University of Manchester, Wilmslow Road, Manchester M20 4BX, UK;Manchester Institute of Biotechnology and the School of Chemistry, 131 Princess Street, The University of Manchester, Manchester M1 7DN, UK

关键词: heparin;    oligosaccharide;    iduronate;    GAG mimetic;   

DOI  :  10.3390/molecules20046167

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.