Physicochemical properties and antitumor activities for sulfated derivatives of lentinan

Five fractions of lentinan, a β-(1→3)-d-glucan bearing β-(1→6)-d-glucopyranosyl branches, were treated with chlorosulfonic acid for 90 min at 60 °C in pyridine medium to synthesize water-soluble sulfated derivatives having the substitution degree of 1.44–1.76. The 13C NMR spectra of the sulfated β-glucans indicated that the C-6 position was preferentially substituted by the sulfate groups. The values of the weight-average molecular weight (Mw), radius of gyration (〈s2〉z1/2), and intrinsic viscosity ([η]) of the sulfated lentinan fractions were determined by size-exclusion chromatography with multi-angle laser light scattering (SEC–MALLS) and viscometry in 0.15 M aq NaCl at 25 °C, respectively. The dependence of [η] on Mw for the sulfated lentinan was found to be [η] = 8.93 × 10−3Mw0.73±0.02 (mL/g) in 0.15 M aq NaCl (for Mw ranging from 14.6 × 104 to 50.4 × 104). On the basis of the Yamakawa–Fujii–Yoshizaki (YFY) theory, the conformational parameters of the sulfated lentinan were calculated as 950 nm−1 for the molar mass per unit contour length (ML), 4.8 nm for the persistence length (q), and 13.9 for the characteristic ratio (C∞), indicating relatively extended single flexible chains in solution. The sulfated glucan fractions exhibited in vitro antiproliferative activities against sarcoma 180 (S-180) cells, and their inhibition ratios were lower than that of the triple-helix lentinan, but higher than that for the one with single random-coil lentinan chains.

Five fractions of lentinan, a triple-helical β-(1→3)-d-glucan, were reacted to synthesize sulfated derivatives. The in vitro test revealed that the chain stiffness and introduction of sulfate groups could enhance their antitumor activities, compared to LF-D-1 with single flexible chains.Figure optionsDownload as PowerPoint slide