Synthesis of lipid A and its analogues for investigation of the structural basis for their bioactivity

DOI DOI Web Site PubMed 被引用文献10件
  • Yukari Fujimoto
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan
  • Yo Adachi
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan
  • Masao Akamatsu
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan
  • Yoshiyuki Fukase
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan
  • Mikayo Kataoka
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan
  • Yasuo Suda
    Department of Nanostructure and Advanced Materials, Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan
  • Koichi Fukase
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan, -u.ac.jp
  • Shoichi Kusumoto
    Department of Chemistry, Graduate School of Science, Osaka University, Toyonaka, Japan

書誌事項

公開日
2005-12
権利情報
  • https://journals.sagepub.com/page/policies/text-and-data-mining-license
DOI
  • 10.1177/09680519050110060901
  • 10.1179/096805105x76841
公開者
SAGE Publications

この論文をさがす

説明

<jats:p> As a step to elucidate the structural requirements for the endotoxic and antagonistic activity of lipid A derivatives, we have focused, in the present study, on the effects of the acyl moieties and acidic groups at the 1- and 4′- positions. We synthesized a new analogue corresponding to Rubrivivax gelatinosus lipid A, which has a characteristic symmetrical distribution of acyl groups on the two glucosamine residues with shorter acyl groups (decanoyl groups [C<jats:sub>10</jats:sub>] and lauryl groups [C<jats:sub>12</jats:sub>]) than Escherichia coli lipid A. Carboxymethyl analogues in which one of the phosphates was replaced with a carboxymethyl group were also synthesized with different distribution of acyl groups. Biological tests revealed that the distribution of acyl groups strongly affected the 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 demonstrated that when the lipid A has shorter (C<jats:sub>10</jats:sub>, C<jats:sub> 12</jats:sub>) hexa-acyl groups, the bioactivity of lipid A is easily affected with small structural difference, such as the difference of acidic group or the distribution of acyl groups, and the bioactivity changes from endotoxic to agonistic or vice versa at this structural boundary for the bioactivity. We also designed, based on molecular mechanics calculations, and synthesized lipid A analogues possessing acidic amino acid residues in place of the non-reducing end phosphorylated glucosamine. Definite switching of the endotoxic or antagonistic activity was also observed depending on the difference of the acidic groups (phosphoric acid or carboxylic acid) in the lipid A analogues. </jats:p>

収録刊行物

被引用文献 (10)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ