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 beta-SQDG-C(18:0) (1,2-di-O-stearoyl-3-O-(6-deoxy-6-sulfo-beta-d-glucopyranosyl)-sn-glycerol), for example, has a potent inhibitory effect on DNA polymerases. We investigated the properties of the vesicle form of beta-SQDG-C(18:0) as the monomer has low solubility in water. The structure of the beta-SQDG-C(18:0) vesicles are highly influenced by NaCl concentration in preparation process. At low NaCl concentrations, the beta-SQDG-C(18:0) vesicles have high surface curvature and form small unilamellar vesicles. Increases in NaCl concentration, resulted in decreased surface curvature and a tendency for beta-SQDG-C(18:0) to form large multilamellar vesicles. The small unilamellar vesicles showed a potent inhibitory effect on DNA polymerase beta, 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 beta activity than non-extruded vesicles. beta-SQDG-C(18:0) vesicles, especially those of small size, were effective in DNA polymerase inhibition and are expected to have high applicability in DNA polymerase study.
Matsumoto
Kenjiro
K
Department of Applied Biological Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba-ken 278, Japan.
Sakai
Hideki
H
Takeuchi
Ryo
R
Tsuchiya
Koji
K
Ohta
Keisuke
K
Sugawara
Fumio
F
Abe
Masahiko
M
Sakaguchi
Kengo
K
D002152:Calorimetry, Differential Scanning; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006017:Glycolipids / Q000737:chemistry / Q000494:pharmacology*; D008027:Light; D046529:Microscopy, Electron, Transmission; D012542:Scattering, Radiation; D013499:Surface Properties
D004791:Enzyme Inhibitors; D006017:Glycolipids; C013694:sulfoquinovosyl diglyceride; D019951:DNA Polymerase beta