The complex heterogeneity of natural H/HS oligosaccharides means that defining the roles of specific sequences - essential for providing designed mimetics for potential therapeutic applications  - is best addressed by chemical synthesis of a diversity of structurally defined sequences. We describe here our syntheses of a range of heparin-type oligosaccharides (up to dodecasaccharide lengths) with pre-installed diversity to investigate alternative sulfation patterns, which has enabled biological evaluation (in vitro and in vivo) of a matrix of these synthetic oligosaccharides for growth-factor binding, cell proliferation and migration, and cell signalling experiments, the conclusions of which are presented here. We have also developed syntheses to provide versatile new end-labellable oligosaccharides, applicable to a range of conjugation and labelling strategies. This includes using a tetrasaccharide-module approach to rapidly access an end-modified bioactive dodecasaccharide then employed for specific 3H-labelling enabling us to conduct new in vivo organ distrobution and PK studies.

Chemical synthesis, site-specific labeling, and biological evaluation/PK of heparan sulphate oligosaccharides

245th National Meeting (2013)

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