GAGomic : Synthetic Tricks, Mimetics for Analytics and futur(istic) Therapeutics

摘要

Glycosaminoglycans are linear and sulphated polysaccharides, expressed at the cell surface and displaying one of the highest information content amongst all biopolymers. As an example, the theoretical molecular diversity for Heparan Sulphate (HS) octasaccharide fragments is higher than 10~6, with the presumed aim of promoting selective interactions with HS binding proteins (HSbps). GAGomics aims at establishing new HS-protein interaction as relevant therapeutic targets. In this field, beside the fully characterized heparin/AT-III interaction,1 the elucidation of the epimerization and sulphation pattern leading to tight and specific binding of an HS fragment to a new therapeutic target is hampered by: 1) the low occurrence of such fragments at the cell surface; 2) the fact that over-sulphation often abolish the specificity of the binding without affecting its intensity.