Synthetic probes for understanding glycosaminoglycan recognition and signaling in the brain

Abstract

Glycosaminoglycans (GAGs) comprise a large family of sulfated polysaccharides that regulate diverse biol. events such as embryonic development, viral invasion, cancer metastasis, and spinal cord injury. Assembled from repeating disaccharide subunits, GAGs exhibit subtle variations in stereochem., chain length, and patterns of sulfation. This structural diversity is thought to enable the generation of a large no. of protein-binding motifs. We will describe the synergistic application of org. chem. and neurobiol. to understand how specific GAG structures interact with protein receptors in the brain. In addn., we will discuss recent work on GAG-based polymer mimetics, which have enabled the first explorations into the importance of macromol. structure on GAG function. These mimetics may also provide agents for modulating specific GAG-mediated processes in vivo. By combining synthetic org. chem., polymer chem., computational chem., and mol. and cellular neurobiol., our studies provide mechanistic insights into how GAGs regulate proteins and signaling events that underlie key processes such as neurite outgrowth, axon regeneration, and neural circuit formation.