Correlation between the antitumor activity of a polysaccharide schizophyllan and its triple-helical conformation in dilute aqueous solution

Yanaki, Toshio; Ito, Wataru; Tabata, Kengo; Kojima, Takemasa; Norisuye, Takashi; Takano, Noriko; Fujita, Hiroshi

doi:10.1016/0301-4622(83)80018-0

Cited by 134 publications

(61 citation statements)

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“…Among these, the single-helix and triple-helix have been considered the biologically active forms, however, it is unclear which is the most active form. Studies evaluating the molecular weight dependence of antitumor activity have suggested that the triple-helix form is the most potent conformer of schizophyllan (SPG) (10,11). However, other studies, using solid state 13 C NMR spectroscopy, have suggested that for antitumor activity (3,12,13) and the production of tumor necrosis factor, nitric oxide, and hydrogen peroxide by macrophage (14,15), the single-helix is the potent conformer (15).…”

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confidence: 97%

Observation of a Partially Opened Triple-helix Conformation in 1→3-β-Glucan by Fluorescence Resonance Energy Transfer Spectroscopy

Young¹,

Dong²,

Jacobs³

2000

Journal of Biological Chemistry

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This study used fluorescence resonance energy transfer (FRET) spectroscopy as an indirect method to investigate the effect of NaOH treatment on the conformation of a triple-helix (133)-␤-D-glucan and then evaluated the effect of conformation on biological activity. Previous studies have suggested that treatment of the triple-helix glucans with NaOH produces single-helix conformers. FRET spectra of the triple-helix glucan, laminarin, doubly labeled with 1-aminopyrene as donor probe and fluorescein-5-isothiocyanate as acceptor probe attached at the reducing end, showed that a partially opened triplehelix conformer was formed on treatment with NaOH. Increasing degrees of strand opening was associated with increasing concentrations of NaOH. Based on these observations we propose that a partially opened triplehelix rather than a single helix, is formed by treating the triple-helix glucans with NaOH. After neutralizing the NaOH, changes in FRET indicated that the partially opened conformer gradually reverts to the triple-helix over 8 days. Laminarian was stabilized at different degrees of partial opening and its biological activity examined using the Limulus amebocyte lysate assay and nitric oxide production by alveolar macrophage. Both Limulus amebocyte lysate activity and nitric oxide production were related to the degree of opening of the triple-helix. Partially open conformers were more biologically active than the intact triple-helix.(133)-␤-D-Glucans have been shown to systemically enhance the immune system, resulting in antitumor, antibacterial, and wound healing activities (1). Differences in these activities are thought to be related to three factors: molecular conformation, the degree of branching, and the molecular weight (M r ) (2). Studies have shown that high M r (100,000 -200,000 g/mol) glucans with a degree of branching of 0.20 -0.33 are most active (2), however, data describing the effects of molecular conformation on biological activity are less clear. This is in part due to the lack of adequate methodology to characterize the tertiary structure of glucans.Most spectroscopic techniques only provide data about the secondary structure of glucans. Methods such as solid state 13 C NMR spectroscopy (3) or multi-angle laser-light scattering (4) have had some success in relating the tertiary structure of glucans to their conformation based biological activity, however, their use is limited by availability, cost, and efficacy for evaluating glucan structure in solution. A direct observation technique, such as x-ray crystallography would assist in understanding glucan structure and its biological relevance; however, it is difficult to crystallize glucans and only a limited number of these studies have been done (5-7).Fluorescence resonance energy transfer (FRET) 1 is a phenomenon of non-radioactive energy transfer over relatively long distances that has been used to characterize the spatial relationship of donor-and acceptor-labeled molecules in biological systems (8). If a system contains two fluorophores an...

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confidence: 97%

Observation of a Partially Opened Triple-helix Conformation in 1→3-β-Glucan by Fluorescence Resonance Energy Transfer Spectroscopy

Young¹,

Dong²,

Jacobs³

2000

Journal of Biological Chemistry

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“…The difference may be caused by the chemical difference between PS-K and SPG. The former is composed of protein-bound polysaccharides, but the latter is formed of pure polyglycan (25,44,48). The results of the biophysical studies of these workers showed that a maculomolecule of SPG in dilute aqueous solution has a triple-herical conformation 3 nm in width.…”

Section: Discussionmentioning

confidence: 99%

Histological and cytochemical studies on the distribution of schizophyllan glucan (SPG) in cancer-inoculated animals. I. Differences in distribution and antitumor activity of 3H-SPG in sarcoma-180 inoculated females between ICR and DBA mice.

Mizuhira

Ono

Yokofujita

et al. 1985

Acta Histochem. Cytochem

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“…This branching point increase their antitumoral and immunomodulating effects (BarretoBergter & Gorin, 1983). It is well established that the structural composition offers a higher capacity for carrying biological information, because they have a greater potential for structural variability, specially related to the triple-helical tertiary conformation (Yanaki et al, 1983). A good example of a preventive effect is given by a Japanese study on their popular edible and medicinal mushroom Hypsizygus marmoreus (Ikekawa, 2001).…”

Section: Immunomodulatorsmentioning

confidence: 99%

Biosynthesis, Purification and Biotechnological Use of Exopolysaccharides Produced by Lactic Acid Bacteria

Werning¹,

Notararigo²,

Nacher³

et al. 2012

Food Additive

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Correlation between the antitumor activity of a polysaccharide schizophyllan and its triple-helical conformation in dilute aqueous solution

Cited by 134 publications

References 13 publications

Observation of a Partially Opened Triple-helix Conformation in 1→3-β-Glucan by Fluorescence Resonance Energy Transfer Spectroscopy

Observation of a Partially Opened Triple-helix Conformation in 1→3-β-Glucan by Fluorescence Resonance Energy Transfer Spectroscopy

Histological and cytochemical studies on the distribution of schizophyllan glucan (SPG) in cancer-inoculated animals. I. Differences in distribution and antitumor activity of 3H-SPG in sarcoma-180 inoculated females between ICR and DBA mice.

Biosynthesis, Purification and Biotechnological Use of Exopolysaccharides Produced by Lactic Acid Bacteria

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