Glycosaminoglycans (GAG) play decisive roles in various cardio-vascular &
cancer-associated processes. Changes in the expression of GAG fine structures, attributed to deregulation of their biosynthetic and catabolic
enzymes, are hallmarks of vascular dysfunction and
tumor progression. The wide spread role of GAG chains in blood clotting, wound healing and
tumor biology has led to the development of modified GAG chains, GAG binding
peptides and GAG based
enzyme inhibitors as therapeutic agents.
Xylosides, carrying hydrophobic aglycone, are known to induce GAG biosynthesis in various systems. Given the important roles of GAG chains in vascular and
tumor biology, we envision that RGD-conjugated
xylosides could be targeted to activated endothelial and
cancer cells, which are known to express α(v)β(3)
integrin, and thereby modulate the
pathological processes. To accomplish this vision,
xylose residue was conjugated to linear and
cyclic RGD containing
peptides using click chemistry. Our results demonstrate that RGD-conjugated
xylosides are able to prime GAG chains in various cell types, and future studies are aimed toward evaluating potential utility of such
xylosides in treating
myocardial infarction as well as
cancer-associated thrombotic complications.