Artículo
High-Mannose Oligosaccharide Hemimimetics that Recapitulate the Conformation and Binding Mode to Concanavalin A, DC-SIGN and Langerin
Título alternativo | Herrera Gonzáles, Irene |
Autor/es | Herrera González, Irene
González Cuesta, Manuel Thépaut, Michel Laigre, Eugénie Goyard, David Rojo, Javier García Fernández, José Manuel Ortiz Mellet, Carmen |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2023-10-12 |
Fecha de depósito | 2024-06-17 |
Publicado en |
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Resumen | The “carbohydrate chemical mimicry” exhibited by sp2-iminosugars has been utilized to develop practical syntheses for analogs of the branched high-mannose-type oligosaccharides (HMOs) Man3 and Man5. In these compounds, the ... The “carbohydrate chemical mimicry” exhibited by sp2-iminosugars has been utilized to develop practical syntheses for analogs of the branched high-mannose-type oligosaccharides (HMOs) Man3 and Man5. In these compounds, the terminal nonreducing Man residues have been substituted with 5,6-oxomethylidenemannonojirimycin (OMJ) motifs. The resulting oligomannoside hemimimetic accurately reproduce the structure, configuration, and conformational behavior of the original mannooligosaccharides, as confirmed by NMR and computational techniques. Binding studies with mannose binding lectins, including concanavalin A, DC-SIGN, and langerin, by enzyme-linked lectin assay and surface plasmon resonance revealed significant variations in their ability to accommodate the OMJ unit in the mannose binding site. Intriguingly, OMJMan segments demonstrated “in line” heteromultivalent effects during binding to the three lectins. Similar to the mannobiose (Man2) branches in HMOs, the binding modes involving the external or internal monosaccharide unit at the carbohydrate binding-domain exist in equilibrium, facilitating sliding and recapture processes. This equilibrium, which influences the multivalent binding of HMOs, can be finely modulated upon incorporation of the OMJ sp2-iminosugar caps. As a proof of concept, the affinity and selectivity towards DC-SIGN and langerin were adjustable by presenting the OMJMan epitope in platforms with diverse architectures and valencies. |
Agencias financiadoras | Agencia Estatal de Investigación. España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) European Cooperation in Science and Technology (COST) Junta de Andalucía Grenoble Partnership for Structural Biology (PSB). France French Infrastructure for Integrated Structural Biology (FRISBI). France Grenoble alliance for integrated structural and cellular biology (GRAL). France University Grenoble Alpes Graduate School. France |
Identificador del proyecto | PID2019-105858RB-I00
PID2020-118403GB-I00 PID2021-125094NB-I00 PID2021-124247OB-C21 PID2022-141034OB-C21 LYCONanoPROBES CM18132 US-1380698 P20_00515 FRISBI ANR-10-INBS-05-02 CBH-EUR-GS ANR-17-URE0003 |
Cita | Herrera González, I., González Cuesta, M., Thépaut, M., Laigre, E., Goyard, D., Rojo, J.,...,Ortiz Mellet, C. (2023). High-Mannose Oligosaccharide Hemimimetics that Recapitulate the Conformation and Binding Mode to Concanavalin A, DC-SIGN and Langerin. Chemistry - A European Journal, 30 (2), e202303041. https://doi.org/10.1002/chem.202303041. |
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