D. Ofman et al., FREE-RADICAL INDUCED OXIDATIVE DEPOLYMERIZATION OF CHONDROITIN SULFATE AND DERMATAN SULFATE, Carbohydrate polymers, 33(1), 1997, pp. 47-56
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.