Total synthesis of escherichia coli lipid A

Imoto, Masahiro; Yoshimura, Hidetoshi; Sakaguchi, Nobuki; Kusumoto, Shoichi; Shiba, Tetsuo

doi:10.1016/s0040-4039(00)98548-4

Cited by 178 publications

(85 citation statements)

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“…Both of these lipid As, the Salmonella-type heptaacylated and E. coli-type hexaacylated forms, had been successfully synthesized chemically in the past (12)(13)(14), and their biological properties had been carefully tested by many investigators (15)(16)(17)(18)(19)(20). The Salmonella-type lipid A had been demonstrated to be very active in mice and rabbits and subsequently had been thought to be a typical lipid A (18 -20) along with that from E. coli.…”

Section: Discussionmentioning

confidence: 99%

“…Escherichia coli-and Salmonella-type lipid A have the most typical lipid A structures so far defined, and both have been synthesized chemically (12)(13)(14) and well characterized biologically by many investigators (15)(16)(17)(18)(19)(20). The chemical structure of these lipid As consists of a hexa-and heptaacylated diglucosamine bearing six and seven fatty acids, respectively, as shown in Fig.…”

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confidence: 99%

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Salmonella-Type Heptaacylated Lipid A Is Inactive and Acts as an Antagonist of Lipopolysaccharide Action on Human Line Cells

Tanamoto

Azumi

2000

The Journal of Immunology

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The stimulation of both THP-1 and U937 human-derived cells by Salmonella lipid A preparations from various strains, as assessed by TNF-α induction and NF-κB activation, was found to be very low (almost inactive) compared with Escherichia coli lipid A, but all of the lipid As exerted strong activity on mouse cells and on Limulus gelation activity. Experiments using chemically synthesized E. coli-type hexaacylated lipid A (506) and Salmonella-type heptaacylated lipid A (516) yielded clearer results. Both lipid A preparations strongly induced TNF-α release and activated NF-κB in mouse peritoneal macrophages and mouse macrophage-like cell line J774-1 and induced Limulus gelation activity, although the activity of the latter was slightly weaker than that of the former. However, 516 was completely inactive on both THP-1 and U937 cells in terms of both induction of TNF-α and NF-κB activation, whereas 506 displayed strong activity on both cells, the same as natural E. coli LPS. In contrast to the action of the lipid A preparations, all the Salmonella LPSs also exhibited full activity on human cells. However, the polysaccharide portion of the LPS neither exhibited TNF-α induction activity on the cells when administered alone or together with lipid A nor inhibited the activity of the LPS. These results suggest that the mechanism of activation by LPS or the recognition of lipid A structure by human and mouse cells may differ. In addition, both 516 and lipid A from Salmonella were found to antagonize the 506 and E. coli LPS action that induced TNF-α release and NF-κB activation in THP-1 cells.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Salmonella-Type Heptaacylated Lipid A Is Inactive and Acts as an Antagonist of Lipopolysaccharide Action on Human Line Cells

Tanamoto

Azumi

2000

The Journal of Immunology

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“…The synthesis of hexaacyl lipid A (preparation 506) has been described [2]. The heptaacyl lipid A (preparation 516) was prepared according to the same synthetic strategy by coupling of the two monosaccharide components, i.e.…”

Section: Synthetic Lipid Amentioning

confidence: 99%

Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A

Galanos

Lüderitz

Freudenberg

et al. 1986

European Journal of Biochemistry

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A synthetic lipid A (preparation 516), containing seven acyl groups and representing one component of natural free lipid A of Salmonella minnesota R595, has been investigated for biological activity in a number of endotoxin test systems. It was found that the synthetic preparation was, in typical in vivo endotoxin tests (lethality, pyrogenicity, Shwartzman reactivity) as well as in its antigenicity and macrophage activation capacity, significantly less active than natural Salmonella lipid A. However, in other in vitro assay systems (B-cell mitogenicity, complement activation, timulus amoebocyte lyzate gelation) it expressed similar activity as Salmonella lipid A.Lipid A represents the endotoxic principle of lipopolysaccharides from which it can be released and isolated by mild acid treatment. Lipid A (in its free or bound form) consists of a heterogeneous mixture of structurally closely related molecular species. The main component of free lipid A of Escherichia coli F515 (Re mutant) represents a hexaacyl lipid A containing the bisphosphorylated glucosamine disaccharide backbone substituted with six acyl residues, i.e. one each of dodecanoic and tetradecanoic acid and four of (R)-3-hydroxytetradecanoic acid, the fatty acids being located at specific positions [l] (see Fig. 1 A). This hexaacyl E. colilipid A has recently been chemically synthesized [2] and the synthetic material, preparation 506, has been shown to be endotoxically fully active, its biological potency being indistinguishable from that of natural E. coli lipid A [3 -51.Analytical stuhes performed with free lipid A from Salmonella minnesota R595 (Re mutant) led to the recognition of a basically identical structure except that it contains an additional hexadecanoic acid (Fig. 1 B). It was found, however, that this fatty acid is not present in stoichiometric amounts [l] and that the heptaacyl lipid A species represents, depending on the bacterial batch, only a fraction of about 20-70% of the microheterogeneous lipid A preparation. Other molecules in the mixture contain smaller numbers of acyl residues and hence resemble or are identical to the E. coli lipid A [6]. Recently, that molecular species of Salmonella lipid A which contains seven acyl residues (heptaacyl lipid A), has been chemically synthesized and termed preparation 516 (Shiba et al., unpublished MATERIAL AND METHODS Bacterial lipid AFree lipid A from S. minnesota R595 (Re mutant) and E. coli F515 (Re mutant) was prepared by treatment of the respective Iipopolysaccharide with 0.1 M acetate buffer (pH 4.4, 100°C) according to [7]. The preparations were freed of low-molecular-mass cations as described earlier and used in the triethylammonium salt form [S]. Synthetic lipid AThe synthesis of hexaacyl lipid A (preparation 506) has been described [2]. The heptaacyl lipid A (preparation 516) was prepared according to the same synthetic strategy by coupling of the two monosaccharide components, i.e. 2 -glucopyranoside to yield the 1,6-linked disaccharide (T. Shiba, unpublished). For conversion in...

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“…Chemical modifications of the lipid A structure have been made to decrease the toxicity without reducing adjuvant activity. Synthetic monophosphoryl lipid A of E coli has been synthesized by lmoto et al (38), while Ribi et al (14) chemically have removed the phosphate moiety from the C-1 position of the toxic diphosphoryllipid A of salmonella. Monophosphoryllipid A is less toxic than the diphosphoryl molecule, but retains much of the adjuvant and mitogenic activity of LPS, and induces nonspecific protection against bacterial infections (14).…”

Section: Lipopolysaccharide and Monophosphoryl Lipid Amentioning

confidence: 99%

Adjuvants for a New Generation of Vaccines

Allison¹,

Byars²

1992

Canadian Journal of Infectious Diseases

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for a new generation of vaccines. Can J Infect Dis 1992;3(Suppl B):84B-93B. Subunit antigens of viruses and other infectious agents in their natural configuration can be produced by recombinant DNA technology. To elicit protective immunity such antigens have to be admirustered with adjuvants that elicit cell-mediated immunity, including genetically restricted cytotoxicity, and that pr oduce high alfmity antibodies of protective isotypes. Antibodies of such isotypes (immunoglobulin G2a [IgG2a] in the mouse and IgG I in humans) efficiently activate complement and eiTect antibody-dependent cell-mediated cytotoxicity. Naturally occurring adjuvants such as lipopolysaccharide and muramyl dipeptide (MOP) are pyrogenic and produce uveitis and arthritis in susceptible experimental animal and human recipients. Synthetic analogues of MOP and monophosphoryl lipid A (MPL) retain adjuvant activity with reduced side eiTects. Adjuvants increase the expression of class II major histocompatibility complex on antigen-presenting cells and cytokine production: interferon-gamma augments the production of IgG2a antibod ies in the mouse. Dispersion of antigens in water-oil emulsions, immunestimulating complexes or liposomes also increases immunogenicity. at least partly by targeting antigens to antigen-presenting cells. Inclusion of MOP analogues or MPL in such systems constitutes adjuvant formu lations. such as MOP-A. When used with a variety of recombinant and other subunit antigens. such adjuvants elicit protective immunity in experimental animals. This strategy improves vaccines already in use (eg, inJl uenza and hepatitis B) and makes possible new vaccines (herpesviruses, simian and human immunodeficiency viruses. respiratory syncytial virus and acellular pertussis).

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Total synthesis of escherichia coli lipid A

Cited by 178 publications

References 9 publications

Salmonella-Type Heptaacylated Lipid A Is Inactive and Acts as an Antagonist of Lipopolysaccharide Action on Human Line Cells

Salmonella-Type Heptaacylated Lipid A Is Inactive and Acts as an Antagonist of Lipopolysaccharide Action on Human Line Cells

Biological activity of synthetic heptaacyl lipid A representing a component of Salmonella minnesota R595 lipid A

Adjuvants for a New Generation of Vaccines

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