Synthesis and biological activities of a library of glycosaminoglycans mimetic oligosaccharides

Biologically active oligosaccharides related to glycosaminoglycans are accumulating increased attention because of their therapeutic potential and for their value in mechanistic studies Heparan mimetics (HMs) are a family of dextran based polymer known to mimic the properties of glycosaminoglycans and particularly those of heparan sulfates as to interact with heparin binding proteins HMs have shown to stimulate tissue repair in various animal models Here we use different methods to depolymerize HMs in order to produce a library of related oligosaccharides and study their biological activities Since HMs were resistant to endoglycanases activities depolymerization was achieved by chemical approaches In vitro biological studies showed that HM oligosaccharides can differentially potentiate FGF-2 mitogenic and antithrombotic activities In vivo a selected oligosaccharide (H-dp12) showed to be able to regenerate tissue almost as well as the related polymeric product The very low anticoagulant activity and high biological activity of low mass oligosaccharides give to these products a new therapeutic potential (C) 2010 Elsevier Ltd All rights reserved