STUDIES ON INTERRELATION OF STRUCTURE AND ANTI-TUMOR EFFECTS OF POLYSACCHARIDES - ANTI-TUMOR ACTION OF PERIODATE-MODIFIED, BRANCHED (1-]3)-BETA-D-GLUCAN OF AURICULARIA-AURICULA-JUDAE, AND OTHER POLYSACCHARIDES CONTAINING (1-]3)-GLYCOSIDIC LINKAGES

Antitumor activities of two (1 .fwdarw. 6)-branched (1 .fwdarw. 3)-.beta.-D-glucans, isolated from the fruiting body of A. auricula-judae (kikurage, an edible mushroom), and other branched polysaccharides containing a backbone chain of (1 .fwdarw. 3)-.alpha.-D-glucosidic or (1 .fwdarw. 3)-.alpha.-D-mannosidic linkages [and their corresponding (1 .fwdarw. 3)-D-glycans, derived by mild, Smith degradation] were compared. Among these polysaccharides, a water-soluble, branched (1 .fwdarw. 3)-.beta.-D-glucan (glucan I) of A. auricula-judae exhibited potent, inhibitory activity against implanted sarcoma 180 solid tumor in mice. The alkali-insoluble, branched (1 .fwdarw. 3)-.beta.-D-glucan (glucan II), a major constituent of the fruiting body, showed essentially no inhibitory activity. When the latter glucan, having numerous branches attached, was modified by controlled, periodate oxidation, borohydride reduction, and mild, acid hydrolysis, the resulting, water-soluble, degraded glucan, having covalently linked polyhydroxy groups attached at O-6 of the (1 .fwdarw. 3)-linked D-glucosyl residues, exhibited potent antitumor activity. Further investigations using the glucan-polyalcohol indicated that the attachment of the polyhydroxy groups to the (1 .fwdarw. 3)-.beta.-D-glucan backbone may enhance the antitumor potency of the glucan. Partial introduction of carboxymethyl groups into glucan II (d.s., 0.47-0.86), which altered the insolubility property, failed to enhance the antitumor activity. The interrelation between the antitumor activity and the structure of the branched (1 .fwdarw. 3)-.beta.-D-glucan is discussed, on the basis of methylation and 13C-NMR studies of the periodate-modified glucans.