Effective form of sulfoquinovosyldiacyglycerol (SQDG) vesicles for DNA polymerase inhibition

Sulfoquinovosyldiacyglycerol (SQDG) has a wide range of biological activities that make it an attractive compound for the development of new drugs. Chemically synthesized β-SQDG-C18:0 (1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-β-d-glucopyranosyl)-sn-glycerol), for example, has a potent inhibitory effect on DNA polymerases. We investigated the properties of the vesicle form of β-SQDG-C18:0 as the monomer has low solubility in water. The structure of the β-SQDG-C18:0 vesicles are highly influenced by NaCl concentration in preparation process. At low NaCl concentrations, the β-SQDG-C18:0 vesicles have high surface curvature and form small unilamellar vesicles. Increases in NaCl concentration, resulted in decreased surface curvature and a tendency for β-SQDG-C18:0 to form large multilamellar vesicles. The small unilamellar vesicles showed a potent inhibitory effect on DNA polymerase β, whereas the large multilamellar vesicles had no such effect. We investigated further the relationship between vesicle size and activity by preparing smaller vesicles (262, 99 and 43 nm in diameter) using an extrusion technique. These smaller vesicles had a greater inhibitory effect on DNA polymerase β activity than non-extruded vesicles. β-SQDG-C18:0 vesicles, especially those of small size, were effective in DNA polymerase inhibition and are expected to have high applicability in DNA polymerase study.