| Glycosaminoglycans (GAGs) are sulfated, linear, polysaccharides consisting of alternating hexosamine and hexuronic acid residues. Due to their acidic nature, they bind to a variety of proteins thus regulating many physiological processes. Heparin is clinically used as an anticoagulant for the prevention of thrombosis during cardiopulmonary bypass. Heparan sulfate is present in the extracellular basement membrane and has to be broken down by metastatic cells before invasion of a new tissue or organ. Chondroitin sulfates are localized in the extracellular matrix and are important in cell-cell communication. The present work explores the use of GAGs in diagnosis and therapy.;Heparinized matrices containing heparin directionally immobilized through its reducing-end showed enhanced protamine binding capacity when compared to commercial matrices containing non-directionally immobilized heparin. The immobilized heparin chain is extended fully into the solution thus exposing all the binding sites. Heparan sulfate immobilized on microtiter plates was used to develop a high through-put ELISA based assay for the screening of tumor extracts for metastatic potential.;A 7-mer random peptide library was affinity fractionated over heparin-Sepharose and heparan sulfate-Sepharose. Arginine and lysine were enriched in the heparin affinity fractions while glycine, serine, and arginine were enriched in the heparan sulfate affinity fractions, indicating a difference in the sequence requirement for interaction with either polymer. Chondroitin sulfates were modified chemically with a view to alter their anticoagulant and antithrombotic properties and the resulting compounds were analyzed by proton NMR. |
