Chemical structure of Lipid A: Linkage site of acyl groups in the disaccharide backbone

Imoto, Masahiro; Kusumoto, Shoichi; Shiba, Tetsuo; Naoki, Hideo; Iwashita, Takashi; Rietschel, Ernst; Wollenweber, H. W.; Galanos, Chris; Lüderitz, Otto

doi:10.1016/s0040-4039(00)88251-9

Cited by 134 publications

(58 citation statements)

References 7 publications

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“…all the biological activities tested are significantly expressed by compound 3. This compound fulfills nearly completely the structure requirement of the nonreducing sugar moiety of the revised structure of lipid A which has been proposed recently [8,9]. This result is a strong indication that several biological activities of the endotoxin can be clearly expressed solely by the structure of the nonreducing sugar moiety of lipid A.…”

Section: Resultssupporting

confidence: 64%

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Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A

Matsuura

Kojima

et al. 1984

FEBS Letters

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Biological activities of five synthetic lipid A analogues (D-glucosamine derivatives) were examined to elucidate the structure required for expression of the biological activities of endotoxin. Proclotting enzyme of horseshoe crab activation, interferon-inducing and tumor necrosis factor-inducing activities were significantly expressed by an analogue which possesses 4-0-phosphoryl, 3-0-tetradecanoyl and N-tetradecanoyloxytetradecanoyl groups. The results obtained with different analogues show that the 4-0-phosphoryl and N-tetradecanoyloxytetradecanoyl groups are important for expression of the above activities. The effect of 6-0-acylation in preventing the expression of these biological activities is also suggested. Pyrogenic activity was not detected in any of the compounds tested.

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Section: Resultssupporting

confidence: 64%

“…A series of chemically synthesized derivatives of D-glucosamine, which are structurally related to the nomeducing sugar moiety of a newly proposed structure of lipid A [8,9], were examined here for proclotting enzyme of horseshoe crab activation, pyrogenicity and interferon-and TNF-induction.…”

Section: Introductionmentioning

confidence: 99%

Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A

Matsuura

Kojima

et al. 1984

FEBS Letters

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“…This finding was unexpected since it was not in accord with the previous assumption that in enterobacterial lipopolysaccharides dOclA is linked to the hydroxyl group at C-3' of the lipid A backbone [47,481. In a recent study on Escherichia coli free lipid A, however, it was shown that the hydroxyl group in position 3' is acylated and thus cannot represent the linkage point of dOclA [49]. A similar conclusion was also reached in an NMR study on E. coli lipopolysaccharide [50].…”

Section: Discussionmentioning

confidence: 69%

“…The absolute configuration of 3-hydroxytetradecanoic acid was determined by gas-liquid chromatography of the diaste- [49]. In analogy to results obtained with Salmonella lipopolysaccharide [51], it is assumed that the reducing glucosaminyl residue is present as the a anorner and that the 4-amino-4-deoxy-~-arabinopyranosyl group possesses the fl form Table 5.…”

Section: Methylation Analysis Of Partially Degraded Lipopolysucchuridementioning

confidence: 99%

Chemical structure of the lipid A component of the lipopolysaccharide from a Proteus mirabilis Re‐mutant

Sidorczyk

Zähringer²,

Rietschel³

1983

European Journal of Biochemistry

140

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The chemical structure of the lipid A component from the lipopolysaccharide of a Proteus mirabilis Re-mutant (strain R45) was analysed. It consists of a p(l-6)-linked D-glucosamine disaccharide which carries two phosphate groups, one being ester-linked to position 4 of the nonreducing glucosaminyl residue and the other being bound to the glycosidic hydroxyl group of the reducing glucosaminyl residue. The ester-bound phosphate group is quantitatively substituted by a 4-amino-4-deoxy-1,-arabinopyranosyl residue, the glycosidic phosphoryl group appears to be unsubstituted. Two available hydroxyl groups of the disaccharadide (probably at positions 3 and 3') are acylated by approximately 1 mol each of (R)-3-tetradecanoyloxytetradecanoic and (R)-3-hydroxytetradecanoic acid/ mol. The amino group of the nonreducing glucosaminyl residue carries (R)-3-tetradecanoyloxytetradecanoic and that of the reducing residue (R)-3-hydroxytetradecanoic acid. In addition smaller amounts of (R)-3-hexadecanoyloxytetradecanoic acid are present in amide linkage.The attachment site of the oligosaccharide portion to lipid A was also investigated. It was found that the hydroxyl group at position 6 of the nonreducing glucosaminyl residue carries 3-deoxy-~-manno-octu~osonic acid. This indicates that the saccharide portion in this Proteus lipopolysaccharide is linked to lipid A via the primary hydroxyl group in position 6' In the present study, the structure of lipid A from a P. mirabilis Re-mutant (R45) was elucidated by chemical analyses. It will be shown that this structure, as compared to other enterobacterial lipids A, exhibits both common and distinct features.

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“…GlcN I carries at both positions 2 and 3 non-acylated (R)-3-hydroxytetradecanoic acid [9, 1 I]. In free lipid A the hydroxyl groups at positions 4 (GlcN I) and 6' (GlcN 11) are free [12], the latter representing the attachment site of the polysaccharide portion in E. coli [I31 (U. Zahringer and S. Kusumoto, unpublished observations) and other lipopolysaccharides (for literature see [6]). …”

mentioning

confidence: 99%

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

Galanos¹,

Lüderitz²,

Rietschel³

et al. 1985

European Journal of Biochemistry

452

262

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The recently chemically synthesized Escherichia coli lipid A and the natural free lipid A of E. coli were compared with respect to their endotoxic activities in the following test systems: lethal toxicity, pyrogenicity, local Shwartzman reactivity, Limulus amoebocyte lysate gelation capacity, tumour necrotizing activity, B cell mitogenicity, induction of prostaglandin synthesis in macrophages, and antigenic specificity. It was found that synthetic and natural free lipid A exhibit identical activities and are indistinguishable in all tests.Lipopolysaccharides (endotoxins) of gram-negative bacteria which consist of a heteropolysaccharide and a lipid component (termed lipid A) elicit multiple acute pathophysiological effects such as fever, lethality, Shwartzman reactivity, macrophage and B-lymphocyte activation, and other activities [I]. In 1954 it was proposed that for the induction of these effects the polysaccharide portion is dispensable and that the lipid A component represents the active center responsible for the endotoxic properties of lipopolysaccharides [2]. Evidence for this was then obtained in numerous investigations [2 -41 and this concept is now generally accepted.The chemical structure of the lipid A component of several enterobacterial lipopolysaccharides has been analysed during recent years in great detail (for reviews see [5, 61) and it was recognized that lipid A of Escherichiu coli possesses a comparatively simple structure. Free E. coli lipid A consists of a 8(1-6)-linked D-glucosamine disaccharide which is substituted by two phosphoryl groups, one being bound to position 4' of the nonreducing glucosamine residue (GlcN 11) and one being a-linked [7] to the glycosidic hydroxyl group of the reducing glucosaminyl group (GlcN I) (Fig.

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Chemical structure of Lipid A: Linkage site of acyl groups in the disaccharide backbone

Cited by 134 publications

References 7 publications

Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A

Biological activities of chemically synthesized analogues of the nonreducing sugar moiety of lipid A

Chemical structure of the lipid A component of the lipopolysaccharide from a Proteus mirabilis Re‐mutant

Synthetic and natural Escherichia coli free lipid A express identical endotoxic activities

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