First Total Synthesis of the Re-Type Lipopolysaccharide

Yoshizaki, Hiroaki; Fukuda, Naohiro; Kenjiro, Sato; Oikawa, Masato; Fukase, Koichi; Suda, Yasuo; Kusumoto, Shoichi

doi:10.1002/1521-3757(20010417)113:8<1523::aid-ange1523>3.0.co;2-x

Cited by 20 publications

(30 citation statements)

References 48 publications

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“…[19] In addition, a synthetic enteric lipid A containing a di-KDO moiety was a more potent elicitor of TNF-α and IL-6 compared to its parent lipid A. [20] Furthermore, LPS from a nitrogen-fixing symbiont, Rhizobium sin-1 is able to significantly inhibit the E. coli LPS-dependent synthesis of TNF-α by human monocytic cells. [21][22][23][24][25] A comparison of the biological responses of synthetic and isolated lipid A derivatives and R. sin-1 LPS indicated that the KDO moieties are important for optimal antagonistic properties.…”

Section: Introductionmentioning

confidence: 99%

Innate Immune Responses of Synthetic Lipid A Derivatives of Neisseria meningitidis

Zhang

Gaekwad

Wolfert

et al. 2007

Chemistry A European J

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Differences in the pattern and chemical nature of fatty acids of lipid A of Neisseria meningitides lipooligosaccharides (LOS) and Escherichia coli lipopolysaccharides (LPS) may account for differences in inflammatory properties. Furthermore, there are indications that dimeric 3-deoxy-Dmanno-oct-2-ulosonic acid (KDO) moieties of LOS and LPS enhance biological activities. Heterogeneity in the structure of lipid A and possible contaminations with other inflammatory components have made it difficult to confirm these observations. To address these problems, a highly convergent approach for the synthesis of a lipid A derivative containing KDO has been developed, which relies on the ability to selectively remove or unmask in a sequential manner an isopropylidene acetal, 9-fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonate (Alloc), azide, and thexyldimethylsilyl (TDS) ether. The strategy was employed for the synthesis of N. meningitidis lipid A containing KDO (3). Mouse macrophages were exposed to the synthetic compound and its parent LOS, E. coli lipid A (2), and a hybrid derivative (4) that has the asymmetrical acylation pattern of E. coli lipid A, but the shorter lipids of meningococcal lipid A. The resulting supernatants were examined for tumor necrosis factor alpha (TNF-α) and interferon beta (IFN-β) production. The lipid A derivative containing KDO was much more active than lipid A alone and just slightly less active than its parent LOS, indicating that one KDO moiety is sufficient for full activity of TNF-α and IFN-β induction. The lipid A of N. meningitidis was a significantly more potent inducer of TNF-α and IFN-β than E. coli lipid A, which is due to a number of shorter fatty acids. The compounds did not demonstrate a bias towards a MyD88-or TRIF-dependent response.

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Section: Introductionmentioning

confidence: 99%

Innate Immune Responses of Synthetic Lipid A Derivatives of Neisseria meningitidis

Zhang

Gaekwad

Wolfert

et al. 2007

Chemistry A European J

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“…[7][8][9] A small library of artificial lipid A analogs was prepared by employing our affinity separation protocol. 10 Final products were purified by liquid-liquid partition chromatography on Sephadex LH-20 and their structures confirmed by mass spectrometry.…”

Section: Synthesismentioning

confidence: 73%

“…10 Final products were purified by liquid-liquid partition chromatography on Sephadex LH-20 and their structures confirmed by mass spectrometry. [7][8][9] …”

Section: Synthesismentioning

confidence: 99%

Structural basis for endotoxic and antagonistic activities: investigation with novel synthetic lipid A analogs

Kusumoto

Fukase

et al. 2003

J. Endotoxin Res.

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Our early work using homogeneous synthetic preparations demonstrated the presence of a lipid A analog which antagonizes endotoxic activities of LPS and lipid A. The first example was a tetraacylated biosynthetic precursor, now known as precursor Ia or lipid IVa, that contains four 3-hydroxytetradecanoyl moieties linked to the bisphosphorylated disaccharide backbone common to the endotoxic hexa-acyl Escherichia coli lipid A. Various compounds with both endotoxic and antagonistic activities have subsequently been reported from either natural or synthetic sources, but little is known about the factors determining the type of the activities of the respective compounds. To approach this issue, we have synthesized a series of lipid A analogs with various numbers and chain lengths of acyl groups on the backbone. Some were prepared by the aid of a novel affinity separation procedure. The phosphate moieties were also synthetically replaced. Biological tests showed that at least three acyl groups are required for antagonistic activity but one or even both of the phosphates can be replaced with other acidic moieties without losing the activity. The effect of Kdo residues linked to lipid A is also briefly discussed. Molecular dynamics calculations reasonably explain possible conformations required for the biological activity.

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“…Over the years, these and other classes of 2-NHTroc glycosyl donors have been used in glycoside and oligosaccharide synthesis: as trichloroacetimidates, 165,238,258,277, for the synthesis of pyruvated saccharide fragments, 280,304 Lipid A derivatives, 165,281,288,290,294,297,298,305,306 glycopeptides, 277,284,285 lactosaminyl donors, 282,307 Re-type lipopolysaccharides, 289 sialyl Lewis X glycolipids, 291,301 gangliosides, 292 peptidoglycan partial structures, 258,308 thiooligosaccharide analogues 286 of Nod factors, carbohydrate antigens, 295,302 sialyl-trimeric-Lewis X, 300 hyaluronan trisaccharides, 309 meonomycin A analogues, 310 and ceramidated GLA-60 293 derivatives; as fluorides, 282,311,312 for the synthesis of lactosaminyl donors, glycosylamines, 312 and tumor-associated antigen 311 Globo-H; as chlorides; 313 as thioglycosides, 283,286,[314][315][316][317][318][319][320][321][322]…”

Section: Alkoxycarbamoyl Derivatives 2-alkoxycarb-mentioning

confidence: 99%

“…314 Its sensitivity to alcoholysis under basic conditions permits convenient transformations into other carbamates. Removal of the Troc group to liberate the primary amine is typically accomplished by reductive elimination using Zn in AcOH, 259,270,271,277,280,282,283,285,[290][291][292] Zn-Cu alloy in AcOH, 258,288,289,297,298,308,335 Zn and acidic buffer, 293,336 Cd-Pb in AcOH, 309,331,337 or more recently, using (Bu 3 Sn) 2 338 in DMF. The use of Zn-N-methylimidazole, 339 in particular, allows selective deprotection of Troc in the presence of reducible and acid-sensitive functionalities.…”

Section: Alkoxycarbamoyl Derivatives 2-alkoxycarb-mentioning

confidence: 99%

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

Bongat

Demchenko

2007

Carbohydrate Research

199

110

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First Total Synthesis of the Re-Type Lipopolysaccharide

Abstract: Drei aufeinander folgende effiziente Glycosylierungen ausgehend von D‐Glucosamin sind Teil der ersten Totalsynthese des Re‐Typ‐Lipopolysaccharids aus Escherichia coli, eines der einfachsten Lipopolysaccharide, die auf der Oberfläche lebender Bakterien nachgewiesen wurden.

Cited by 20 publications

References 48 publications

Innate Immune Responses of Synthetic Lipid A Derivatives of Neisseria meningitidis

Innate Immune Responses of Synthetic Lipid A Derivatives of Neisseria meningitidis

Structural basis for endotoxic and antagonistic activities: investigation with novel synthetic lipid A analogs

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

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