Development, physicochemical characterization and preclinical efficacy evaluation of a water soluble glucan sulfate derived from Saccharomyces cerevisiae

Autor: Williams, David L., Pretus, Henry A., McNamee, Rose B., Jones, Ernest L., Ensley, Harry E., William Browder, I., Di Luzio, Nicholas R.
Zdroj: Immunopharmacology; November-December 1991, Vol. 22 Issue: 3 p139-156, 18p
Abstrakt: This report describes the development, characterization and preclinical efficacy evaluation of water soluble glucan sulfate. Glucan sulfate was derived from insoluble β-1,3-d-glucan isolated from Saccharomyces cerevisiae. The proposed repeating unit empirical formula of glucan sulfate is [(C6H10O5)05·3H2SO4]n. Two polymer peaks were resolved by aqueous high-performance size exclusion chromatography (HPSEC) with on-line multi-angle laser light scattering (MALLS) photometry and differential viscometry. Peak 1 (Mw= 1 219 697 Da) represents ≈1% of the total polymers, while peak 2 (Mw= 8 884 Da) accounts for ≈ 99% of polymers. 13C-NMR spectroscopy suggests that glucan sulfate polymer strands may be partially cross-linked. Glucan sulfate (250 mg/kg, i.v.) increased (P< 0.01) macrophage vascular clearance of 131I-reticuloendothelial emulsion by 42% (P< 0.01) and in vitro bone marrow proliferation by 46% (P< 0.05). Glucan sulfate (250 mg/kg, i.v.) increased (P< 0.05) median survival time of C57B1/6J mice with syngeneic melanoma B16 or sarcoma M5076. In addition, glucan sulfate immunoprophylaxis increased resistance of mice to challenge with Escherichia coli, Candida albicansor Mouse Hepatitis Virus strain A-59. We concluded that: (1) insoluble β-1,3-d-glucan can be converted to a water soluble sulfated form; (2) glucan sulfate activates macrophages and stimulates bone marrow; (3) glucan sulfate exerts antitumor therapeutic activity, and (4) glucan sulfate immunoprophylaxis will modify the course of experimental infectious disease.
Databáze: Supplemental Index