Selective Sulfation of Chitin Derivatives for Biomedical Functions

The highest antithrombogenic activity was achieved by the N- and O-sulfation of partially N-deacetylated (70%) 6-O-carboxymethyl (0.60)-chitin (SCM-DAC-70) among various modified chitin derivatives. But a O-sulfated 6-O-carobxymethyl-chitin (SCM-chitin) was a quite in- ert heparinoid for the inhibition of blood clotting. It was also suggested that the distribution of N-sulfate and N-acetyl groups on the C-2 position of glucosamine residue might be essential to the selective adsorption of SCM-DAC-70 to antithrombin-III (AT-III) to inhibit thrombin activity. Kinetic evaluations demonstrated the noncompetitive inhibition of thrombin activity by SCM-DAC-70 and competitive inhibition of throm- bin by SCM-DAC-70-AT-III complex. We were unable to find such a specific inhibition by the SCM-DAC-70 complex with blood clotting factors other than AT-III. SCM-chitin was found to inhibit the metasta- sis of cancer cells at about 80–85% without any side effect different from those of heparin. It was suggested that the inhibition of metastasis of B16-BL6 melanoma cells was achieved by bifunctional inhibitions for heparanase and type IV collagenase without growth inhibition of cancer cells.