EFFECTS OF BRANCH DISTRIBUTION AND CHEMICAL MODIFICATIONS OF ANTITUMOR (1-]3)-BETA-D-GLUCANS

A potent antitumor-active branched (1 --> 3)-beta-D-glucan (VVG) purified from fruiting body of Volvariella volvacea and some other glucans were chemically modified to study the enhancement of inhibitory activity on the growth of mouse-transplanted tumors. Conversion of the glucosyl groups substituted at O-6 atoms of the (1 --> 3)-linked D-glucose residues into the corresponding polyhydroxyl groups gave significant enhancement of the original activities both on allogeneic and syngeneic tumors, whereas deletion of the polyhydroxyl groups by mild acid treatment resulted in a great reduction of the activity. When D-glucose residues of the branches were modified to the 3,6-anhydro D-glucose residues by partial sulfation and then alkali treatment, the resulting modified VVG showed essentially no antitumor activity. In connection of the modifications of the branches, a linear (1 --> 3)-beta-D-glucan was modified to epoxylated glucan (degree of substitution, 0.14), which lost its original activity. On the contrary, conversion of the epoxy groups to hydrophilic glycerol groups remarkably enhanced the original antitumor activity. These results confirmed the previous findings that, besides the conformation of (1 --> 3)-beta-glucan backbone, the molecular shape and the distribution pattern of the substituted groups located outside the backbone chains, must also play an important role in exhibiting antitumor action.