| Description |
Heparan sulfate (HS) is a naturally occurring, heterogeneous, linear, sulfated polysaccharide that is known to bind and affect the pharmacokinetics and pharmacodynamics of an expansive array of cytokines, growth factors, cell-surface receptors, and other proteins that govern most biological processes. Despite the fact that heparin - a highly-sulfated, natural heparan sulfate derivative - has been used medically for over eight decades, the structure-activity-relationships between heparan sulfate and its myriad protein targets remain mostly uncharacterized. Because of heparan sulfate's heterogeneity, one of the major obstacles to defining these diverse protein-HS interactions has been the production of size-defined oligosaccharides in quantities sufficient to enable thorough characterization and study in a variety of in vitro and in vivo systems. In this study, a variety of chemical and enzymatic techniques are used in creating a library of heparan sulfate structures, and two novel methods of oligosaccharide preparation - one highly robust for small quantities and one for high yield production - are presented to combat the problem of structure availability that has traditionally limited the study of structure activity relationships governing heparan sulfate's many biological interactions. Finally, examples of in vitro studies of these HS structures are also presented. |
