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dc.contributor.authorCochet, Florent
dc.contributor.authorFacchini, Fabio A.
dc.contributor.authorZaffaroni, Lenny
dc.contributor.authorBillod, Jean-Marc
dc.contributor.authorCoelho, Helena
dc.contributor.authorHolgado, Aurora
dc.contributor.authorBraun, Harald
dc.contributor.authorBeyaert, Rudi
dc.contributor.authorJerala, Roman
dc.contributor.authorJiménez Barbero, Jesús
dc.contributor.authorMartin-Santamaria, Sonsoles
dc.contributor.authorPeri, Francesco
dc.date.accessioned2019-03-21T12:56:34Z
dc.date.available2019-03-21T12:56:34Z
dc.date.issued2019-01-29
dc.identifier.citationScientific Reports 9 : (2019) // Article ID 919es_ES
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10810/32088
dc.description.abstractNew monosaccharide-based lipid A analogues were rationally designed through MD-2 docking studies. A panel of compounds with two carboxylate groups as phosphates bioisosteres, was synthesized with the same glucosamine-bis-succinyl core linked to different unsaturated and saturated fatty acid chains. The binding of the synthetic compounds to purified, functional recombinant human MD-2 was studied by four independent methods. All compounds bound to MD-2 with similar affinities and inhibited in a concentration-dependent manner the LPS-stimulated TLR4 signaling in human and murine cells, while being inactive as TLR4 agonists when provided alone. A compound of the panel was tested in vivo and was not able to inhibit the production of proinflammatory cytokines in animals. This lack of activity is probably due to strong binding to serum albumin, as suggested by cell experiments in the presence of the serum. The interesting self-assembly property in solution of this type of compounds was investigated by computational methods and microscopy, and formation of large vesicles was observed by cryo-TEM microscopy.es_ES
dc.description.sponsorshipTOLLerant project (H2020-MSC-ETN-642157), the Italian Ministry for Foreign Affairs and International Cooperation (MAECI) and Spanish MINECO (CTQ2014-57141-R and CTQ2017-88353-R grants) are acknowledged. Vesna Hodnik of University of Ljubljana for the help with SPR, Sandra Delgado of CIC BioGUNE for the Cryo-TEM images. RJ was partially funded by the research program P4-0176 by the Slovenian Research Agency.es_ES
dc.language.isoenges_ES
dc.publisherNature Publishinges_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/CTQ2014-57141-Res_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/CTQ2017-88353-Res_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectlipopolysaccharide (lps)-binding proteines_ES
dc.subjectlipid-a analogses_ES
dc.subjectreceptor 4es_ES
dc.subjectbiological-activitieses_ES
dc.subjectstructural basises_ES
dc.subjectvaccine adjuvantses_ES
dc.subjectcrystal-structurees_ES
dc.subjectlpses_ES
dc.subjectcd14es_ES
dc.subjectrecognitiones_ES
dc.titleNovel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly propertieses_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holderOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-018-37421-wes_ES
dc.identifier.doi10.1038/s41598-018-37421-w
dc.departamentoesQuímica orgánica IIes_ES
dc.departamentoeuKimika organikoa IIes_ES


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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Except where otherwise noted, this item's license is described as Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.