Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin
DC-SIGN, a lectin, which presents at the surface of immature dendritic cells, constitutes nowadays a promising target for the design of new antiviral drugs. This lectin recognizes highly glycosylated proteins present at the surface of several pathogens such as HIV, Ebola virus, Candida albicans, Myc...
| Autores: | , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2008 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/73498 |
| Acceso en línea: | https://hdl.handle.net/11441/73498 https://doi.org/10.1039/b802144a |
| Access Level: | acceso abierto |
| Palabra clave: | Cell adhesion molecules Lectins C-type Mannose Receptors Cell surface Trisaccharides Ligands |
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Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectinReina, José J.Díaz, IreneNieto, Pedro M.Campillo, Nuria EugeniaPáez, Juan AntonioTabarani, GeorgesFieschi, FranckRojo, JavierCell adhesion moleculesLectinsC-typeMannoseReceptorsCell surfaceTrisaccharidesLigandsDC-SIGN, a lectin, which presents at the surface of immature dendritic cells, constitutes nowadays a promising target for the design of new antiviral drugs. This lectin recognizes highly glycosylated proteins present at the surface of several pathogens such as HIV, Ebola virus, Candida albicans, Mycobacterium tuberculosis, etc. Understanding the binding mode of this lectin is a topic of tremendous interest and will permit a rational design of new and more selective ligands. Here, we present computational and experimental tools to study the interaction of di- and trisaccharides with DC-SIGN. Docking analysis of complexes involving mannosyl di- and trisaccharides and the carbohydrate recognition domain (CRD) of DC-SIGN have been performed. Trisaccharides Manα1,2[Manα1,6]Man 1 and Manα1,3[Manα1,6]Man 2 were synthesized from an orthogonally protected mannose as a common intermediate. Using these ligands and the soluble extracellular domain (ECD) of DC-SIGN, NMR experiments based on STD and transfer-NOE were performed providing additional information. Conformational analysis of the mannosyl ligands in the free and bound states was done. These studies have demonstrated that terminal mannoses at positions 2 or 3 in the trisaccharides are the most important moiety and present the strongest contact with the binding site of the lectin. Multiple binding modes could be proposed and therefore should be considered in the design of new ligands.Ministerio de Ciencia y Tecnología SAF 2003–08003-CO2Ministerio de Educación y Ciencia SAF 2006–13391-CO3Royal Society of Chemistry (Great Britain)Ministerio de Ciencia y Tecnología (MCYT). EspañaMinisterio de Educación y Ciencia (MEC). España2008info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/73498https://doi.org/10.1039/b802144areponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésOrganic and Biomolecular Chemistry, 6 (15), 2743-2754.http://dx.doi.org/10.1039/b802144ainfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/734982026-06-17T12:51:07Z |
| dc.title.none.fl_str_mv |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| title |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| spellingShingle |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin Reina, José J. Cell adhesion molecules Lectins C-type Mannose Receptors Cell surface Trisaccharides Ligands |
| title_short |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| title_full |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| title_fullStr |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| title_full_unstemmed |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| title_sort |
Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin |
| dc.creator.none.fl_str_mv |
Reina, José J. Díaz, Irene Nieto, Pedro M. Campillo, Nuria Eugenia Páez, Juan Antonio Tabarani, Georges Fieschi, Franck Rojo, Javier |
| author |
Reina, José J. |
| author_facet |
Reina, José J. Díaz, Irene Nieto, Pedro M. Campillo, Nuria Eugenia Páez, Juan Antonio Tabarani, Georges Fieschi, Franck Rojo, Javier |
| author_role |
author |
| author2 |
Díaz, Irene Nieto, Pedro M. Campillo, Nuria Eugenia Páez, Juan Antonio Tabarani, Georges Fieschi, Franck Rojo, Javier |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
Ministerio de Ciencia y Tecnología (MCYT). España Ministerio de Educación y Ciencia (MEC). España |
| dc.subject.none.fl_str_mv |
Cell adhesion molecules Lectins C-type Mannose Receptors Cell surface Trisaccharides Ligands |
| topic |
Cell adhesion molecules Lectins C-type Mannose Receptors Cell surface Trisaccharides Ligands |
| description |
DC-SIGN, a lectin, which presents at the surface of immature dendritic cells, constitutes nowadays a promising target for the design of new antiviral drugs. This lectin recognizes highly glycosylated proteins present at the surface of several pathogens such as HIV, Ebola virus, Candida albicans, Mycobacterium tuberculosis, etc. Understanding the binding mode of this lectin is a topic of tremendous interest and will permit a rational design of new and more selective ligands. Here, we present computational and experimental tools to study the interaction of di- and trisaccharides with DC-SIGN. Docking analysis of complexes involving mannosyl di- and trisaccharides and the carbohydrate recognition domain (CRD) of DC-SIGN have been performed. Trisaccharides Manα1,2[Manα1,6]Man 1 and Manα1,3[Manα1,6]Man 2 were synthesized from an orthogonally protected mannose as a common intermediate. Using these ligands and the soluble extracellular domain (ECD) of DC-SIGN, NMR experiments based on STD and transfer-NOE were performed providing additional information. Conformational analysis of the mannosyl ligands in the free and bound states was done. These studies have demonstrated that terminal mannoses at positions 2 or 3 in the trisaccharides are the most important moiety and present the strongest contact with the binding site of the lectin. Multiple binding modes could be proposed and therefore should be considered in the design of new ligands. |
| publishDate |
2008 |
| dc.date.none.fl_str_mv |
2008 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
| format |
article |
| status_str |
acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/11441/73498 https://doi.org/10.1039/b802144a |
| url |
https://hdl.handle.net/11441/73498 https://doi.org/10.1039/b802144a |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Organic and Biomolecular Chemistry, 6 (15), 2743-2754. http://dx.doi.org/10.1039/b802144a |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
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application/pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Royal Society of Chemistry (Great Britain) |
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Royal Society of Chemistry (Great Britain) |
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reponame:idUS. Depósito de Investigación de la Universidad de Sevilla instname:Universidad de Sevilla (US) |
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Universidad de Sevilla (US) |
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idUS. Depósito de Investigación de la Universidad de Sevilla |
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idUS. Depósito de Investigación de la Universidad de Sevilla |
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