リピドAアナローグE5531の形成する会合体について

概要

論文の詳細を見る
E5531, a synthetic disaccharide analog of the lipid A, was dispersed using a novel “pH-jump method”, which involves dispersing E5531 in an alkaline solution (0.003 N NaOH, pH 11.0) at 50°C and then mixing the solution with buffer to neutralize the pH 7.3. The size of the aggregates was approximately 20 nm and the structure was vesiclar. The membrane fluidity of the aggregates increased with increasing the dispersing time in 0.003 N NaOH solution. Using the samples with different membrane fluidity, the pharmacokinetics and ED50 were evaluated after intravenous administration into rats and mice. The data obtained confirmed that the membrane fluidity was correlated with the pharmacokinetics in rats and ED50 in mice. The biological effects of E5531 were investigated. The pyrogenic activity of E5531 was weak and the profile of the increase in the rectal temperature of rabbits was different from that of the USP reference standard endotoxin (ETX). E5531 suppressed the pyrogenicity of ETX in rabbits. In addition, in order to evaluate the effects of E5531 on the cell surface membrane, we used dipalmitoylphosphatidylcholine (DPPC) as a model membrane. E5531 decreased the phase transition temperature of DPPC and increased the fluidity at 37°C. These effects of E5531 on DPPC membrane were different from those of the lipid A from Escherichia coli and Salmonella minnesota.
日本膜学会の論文
2000-03-01