dc.contributor.author | Srivastava, Apoorva D. | |
dc.contributor.author | Unione, Luca | |
dc.contributor.author | Wolfert, Margreet A. | |
dc.contributor.author | Valverde, Pablo | |
dc.contributor.author | Ardá, Ana | |
dc.contributor.author | Jiménez Barbero, Jesús | |
dc.contributor.author | Boons, Geert-Jan | |
dc.date.accessioned | 2021-02-08T09:46:29Z | |
dc.date.available | 2021-02-08T09:46:29Z | |
dc.date.issued | 2020-12-01 | |
dc.identifier.citation | Chemistry – A European Journal 26(67) : 15605-15612 (2020) | es_ES |
dc.identifier.issn | 0947-6539 | |
dc.identifier.issn | 1521-3765 | |
dc.identifier.uri | http://hdl.handle.net/10810/50088 | |
dc.description.abstract | The parasitic worm,Schistosoma mansoni, expresses unusual fucosylated glycans in a stage-dependent manner that can be recognized by the human innate immune receptor DC-SIGN, thereby shaping host immune responses. We have developed a synthetic approach for mono- and bis-fucosylated LacdiNAc (LDN-F and LDN-DF, respectively), which are epitopes expressed on glycolipids and glycoproteins ofS. mansoni. It is based on the use of monosaccharide building blocks having carefully selected amino-protecting groups, facilitating high yielding and stereoselective glycosylations. The molecular interaction between the synthetic glycans and DC-SIGN was studied by NMR and molecular modeling, which demonstrated that the alpha 1,3-fucoside of LDN-F can coordinate with the Ca2+-ion of the canonical binding site of DC-SIGN allowing for additional interactions with the underlying LDN backbone. The 1,2-fucoside of LDN-DF can be complexed in a similar manner, however, in this binding mode GlcNAc and GalNAc of the LDN backbone are placed away from the protein surface resulting in a substantially lower binding affinity. Glycan microarray binding studies showed that the avidity and selectivity of binding is greatly enhanced when the glycans are presented multivalently, and in this format Le(x)and LDN-F gave strong responsiveness, whereas no binding was detected for LDN-DF. The data indicates thatS. mansonihas developed a strategy to avoid detection by DC-SIGN in a stage-dependent manner by the addition of a fucoside to a number of its ligands. | es_ES |
dc.description.sponsorship | This research was supported by the Netherlands Organization for Scientific Research (NWO; TOP-PUNT grant 718.015.003 to G.-J.B.), the Human Frontier Science Program Organization (HFSP; grant LT000747/2018-C to L.U.), the European Research Council (ERC-2017-AdG, project number 788143-RECGLYC-ANMR to J.J.-B.), the Agencia Estatal Investigacion of Spain (AEI; grant RTI2018-094751-B-C21 to J.J.-B.) and the Severo Ochoa Excellence Accreditation (SEV-2016-0644 to J.J.-B.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Wiley | es_ES |
dc.relation | info:eu-repo/grantAgreement/EC/H2020/788143 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-094751-B-C21 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/3.0/es/ | * |
dc.subject | chemical synthesis | es_ES |
dc.subject | glycans | es_ES |
dc.subject | immune modulation | es_ES |
dc.subject | molecular recognition | es_ES |
dc.subject | NMR spectroscopy | es_ES |
dc.subject | C-type Lectins | es_ES |
dc.subject | structural basis | es_ES |
dc.subject | binding | es_ES |
dc.subject | glycomics | es_ES |
dc.subject | affinity | es_ES |
dc.subject | ligand | es_ES |
dc.subject | mechanism | es_ES |
dc.subject | antigens | es_ES |
dc.subject | reveals | es_ES |
dc.subject | fucose | es_ES |
dc.title | Mono and Di-Fucosylated Glycans of the Parasitic Worm S. Mansoniare Recognized Differently by the Innate Immune Receptor DC-SIGN | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This is an open access article underthe terms of Creative Commons Attribution (CC BY-NC 4.0) | es_ES |
dc.rights.holder | Atribución-NoComercial 3.0 España | * |
dc.relation.publisherversion | https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.202002619 | es_ES |
dc.identifier.doi | 10.1002/chem.202002619 | |
dc.contributor.funder | European Commission | |
dc.departamentoes | Química orgánica II | es_ES |
dc.departamentoeu | Kimika organikoa II | es_ES |