Conformation-dependent Change In Antitumor Activity of Linear And Branched (l->3)-/j-d-glucans On The Basis of Conformational Elucidation By Carbon-13 Nuclear Magnetic Resonance Spectroscopy

Abstract

The antitumor activity of (1→3)-fl-D-glucans was tested in order to clarify its conformation-dependent response together with conformational elucidation by carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy. It was shown that the following three conformations, single chain, single helix and triple helix, are readily distinguished by the high-resolution solid-state 13C-NMR method. It turned out that preparations of linear (l-»3)-β-D-glucans of a triple helical conformation were ineffective in the inhibition of tumor growth. These linear (l->3)-D-glucans were converted to an effective form in the inhibition of tumor growth when they were lyophilized from dimethyl sulfoxide (DMSO) solutions as a result of a conformational change from the triple helical to the single chain forms. They were not effective, however, when assayed in DMSO solution. In contrast, it was found that a branched (l->3)-β-n-glucan is effective not only in either saline solutions of the triple helical sample or the lyophilized sample from DMSO, but also in DMSO solution. The aforementioned drastic change in antitumor activity was interpreted in terms of resulting conformational changes as analyzed by the 13C-NMR method. © 1992, The Pharmaceutical Society of Japan. All rights reserved.