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

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13 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)796-819
Number of pages24
JournalBulletin of the Chemical Society of Japan
Volume81
Issue number7
DOIs
Publication statusPublished - 2008 Jul 15
Externally publishedYes

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Lipid A
Bioactivity
Glucosamine
Escherichia coli
Phosphates
Derivatives
Lipids

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Synthesis of Rubrivivax gelatinosus lipid A and analogues for investigation of the structural basis for immunostimulating and inhibitory activities. / Fukase, Yoshiyuki; Fujimoto, Yukari; Adachi, Yo; Suda, Yasuo; Kusumoto, Shoichi; Fukase, Koichi.

In: Bulletin of the Chemical Society of Japan, Vol. 81, No. 7, 15.07.2008, p. 796-819.

Research output: Contribution to journalArticle

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