Synthesis and Assessment of Glycosaminoglycan Priming Activity of Cluster-xylosides for Potential Use as Proteoglycan Mimetics
journal contributionposted on 2013-05-17, 00:00 authored by Vy M. Tran, Thao K. N. Nguyen, Venkataswamy Sorna, Duraikkannu Loganathan, Balagurunathan Kuberan
One of the distinct structural features of many proteoglycans (PGs) is the presence of two or more glycosaminoglycan (GAG) side chains covalently linked to a core protein. Previous studies have shown that the synergistic biological activity of multiple GAG chains, as found in the majority of PGs, cannot be accomplished by the sum of the activities of individual GAG chains. To delineate the biological significance of GAG valency, a number of cluster-xylosides carrying two, three, or four xylose residues on the same scaffold were synthesized using click chemistry. Assessment of cluster-xylosides for their GAG chain priming activity in a cellular system revealed that these cluster-xylosides prime multiple GAG chains per scaffold. Multivalent GAG chains, produced by cluster-xylosides, can better mimic PGs as they carry two or more GAG chains attached to a core protein and therefore can be used as molecular probes to examine the biological significance of GAG multivalency in model organisms.