{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T01:06:59Z","timestamp":1788311219438,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T00:00:00Z","timestamp":1192579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2008,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Differences in the pattern and chemical nature of fatty acids of lipid A of <jats:italic>Neisseria meningitides<\/jats:italic> lipooligosaccharides (LOS) and <jats:italic>Escherichia coli<\/jats:italic> lipopolysaccharides (LPS) may account for differences in inflammatory properties. Furthermore, there are indications that dimeric 3\u2010deoxy\u2010<jats:sc>D<\/jats:sc>\u2010manno\u2010oct\u20102\u2010ulosonic 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\u2010fluorenylmethoxycarbonyl (Fmoc), allyloxycarbonate (Alloc), azide, and thexyldimethylsilyl (TDS) ether. The strategy was employed for the synthesis of <jats:italic>N. meningitidis<\/jats:italic> lipid A containing KDO (<jats:bold>3<\/jats:bold>). Mouse macrophages were exposed to the synthetic compound and its parent LOS, <jats:italic>E. coli<\/jats:italic> lipid A (<jats:bold>2<\/jats:bold>), and a hybrid derivative (<jats:bold>4<\/jats:bold>) that has the asymmetrical acylation pattern of <jats:italic>E. coli<\/jats:italic> lipid A, but the shorter lipids of meningococcal lipid A. The resulting supernatants were examined for tumor necrosis factor alpha (TNF\u2010\u03b1) and interferon beta (IFN\u2010\u03b2) 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\u2010\u03b1 and IFN\u2010\u03b2 induction. The lipid A of <jats:italic>N. meningitidis<\/jats:italic> was a significantly more potent inducer of TNF\u2010\u03b1 and IFN\u2010\u03b2 than <jats:italic>E. coli<\/jats:italic> lipid A, which is due to a number of shorter fatty acids. The compounds did not demonstrate a bias towards a MyD88\u2010 or TRIF\u2010dependent response.<\/jats:p>","DOI":"10.1002\/chem.200701165","type":"journal-article","created":{"date-parts":[[2007,10,17]],"date-time":"2007-10-17T09:50:06Z","timestamp":1192614606000},"page":"558-569","source":"Crossref","is-referenced-by-count":60,"title":["Innate Immune Responses of Synthetic Lipid A Derivatives of <i>Neisseria meningitidis<\/i>"],"prefix":"10.1002","volume":"14","author":[{"given":"Yanghui","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jidnyasa","family":"Gaekwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margreet\u2005A.","family":"Wolfert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geert\u2010Jan","family":"Boons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,12,19]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/scientificamerican1188-126"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/159.2.195"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.3.650"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.13.1.144-166.2000"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/90609"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2003.10.006"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni910"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1139\/o80-018","volume":"58","author":"Jennings H. 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