FREE-RADICAL INDUCED OXIDATIVE DEPOLYMERIZATION OF CHONDROITIN SULFATE AND DERMATAN SULFATE

The glycosaminoglycan (GAG) dermatan sulphate (DS) is a potentially us eful therapeutic for antithrombotic applications. Natural DS is isolat ed as a polymer of a molecular weight of around 25 000. The predominan t disaccharide unit is IdoA-GalNAc4SO(3) but the antithrombotic activi ty is mediated by the binding of heparin cofactor II (HCII) to repeats of IdoA2SO(3)-GalNAc4SO(3). We hoped, in parallel with other bioactiv e GAGs, such as heparin, to improve the phamacological properties of D S by lowering the molecular weight using oxidative free radical depoly merisation. We found indeed that the method gives a smooth and repeata ble reduction in molecular weight using chondroitin sulphate as a mode l system but it appears to selectively attack the disaccharide unit Id oA2SO(3)-GalNAc4SO(3) in DS, severely reducing its activity towards HC II. In the course of these investigations we found that, in contrast t o prior work on heparin, uncharged polysaccharides cannot be used as s tandards for the determination of molecular weight of DS and chondroit in sulphate by high performance sine exclusion chromatography with hig h ionic strength buffers. (C) 1997 Elsevier Science Ltd.