Synthesis of Rubrivivax gelatinosus lipid A and analogues for investigation of the structural basis for immunostimulating and inhibitory activities

Yoshiyuki Fukase, Yukari Fujimoto, Yo Adachi, Yasuo Suda, Shoichi Kusumoto, Koichi Fukase

研究成果: Article査読

16 被引用数 (Scopus)

抄録

To elucidate the structural requirements for the endotoxic and antagonistic activities of lipid A derivatives, we have focused on the effects of the acyl moieties and acidic groups at the 1- and 4′-positions in the present study. We have synthesized new analogues corresponding to Rubrivivax gelatinosus lipid A, which has a characteristic symmetrical distribution of its acyl groups on its two glucosamine residues with shorter acyl groups (decanoyl groups (C10) and lauryl groups (C12)) than Escherichia coli lipid A's. Carboxymethyl (CM) analogues in which one of the phosphates was replaced with a CM group were also synthesized with a different distribution of acyl groups. Biological tests revealed that the acyl group distribution in the lipid A analogue, strongly affected its bioactivity. The synthetic Ru. gelatinosus type lipid A showed potent antagonistic activity against LPS, whereas its 1-O-carboxymethyl analogue showed weak endotoxic activity. These results demonstrate that when lipid A has shorter (C10 and C12) hexa-acyl groups, its bioactivity is more easily affected by small structural differences, such as differences in acidic groups or acyl group distribution, and that they can change bioactivity from endotoxic to agonistic or vice versa at this structural boundary for the bioactivity.

本文言語English
ページ(範囲)796-819
ページ数24
ジャーナルBulletin of the Chemical Society of Japan
81
7
DOI
出版ステータスPublished - 2008 7月 15
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)

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