CHEMICAL SYNTHESIS AND BIOLOGICAL EVALUATION OF CHONDROITIN SULFATE DISACCHARIDES

Abstract

Glycosaminoglycans (GAGs) are heterogeneous polysaccharides comprising of repeating uronic acid and amino sugar disaccharide units. Recently, it was shown that the sulfate groups present in chondroitin sulfate GAGs (CS) encode important functional information for the regulation of physiological processes. However, procurement of pure, homogenous CS motifs for biological evaluation is a challenging task due to isolation difficulty and structural complexity.

To probe the ?sulfation code? in CS, a synthetic strategy was devised to obtain all 16 theoretically possible sulfation patterns in the CS repeat unit. The strategy incorporates orthogonal protecting groups in glucuronic acid and N-acetyl galactosamine precursor units obtained through a divergent approach, prior to modular glycosylation and selective final transformations. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.