Multivalent ligands of the C-type lectin receptor DC-SIGN have emerged as effective antiadhesive agents against various pathogens. Some years ago, we described a hexavalent DC-SIGN ligand, Polyman-26, designed to bridge two of the four binding sites displayed by the receptor. In this work, we present our efforts to accomplish simultaneous coordination of all four carbohydrate binding sites of DC-SIGN through the synthesis of cross-shaped glycodendrimers. The tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assays revealed strong binding avidity towards DC-SIGN and increased selectivity over langerin. Inhibition of DC-SIGN binding to SARS-CoV-2 spike protein and of DC-SIGN mediated Ebola virus trans-infection testifies for the glycodendrimers potential application in infection diseases. The tetravalent platform described here is easily accessible and can be used in modular fashion with different ligands, thus lending itself to multiple applications.

Precision Glycodendrimers for DC-SIGN Targeting / G. Goti, C. Colombo, S. Achilli, C. Vives, M. Thepaut, J. Luczkowiak, N. Labiod, R. Delgado, F. Fieschi, A. Bernardi. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 2022:29(2022 Aug 05), pp. e202200113.1-e202200113.10. [10.1002/ejoc.202200113]

Precision Glycodendrimers for DC-SIGN Targeting

G. Goti
Primo
;
C. Colombo
Secondo
;
A. Bernardi
2022

Abstract

Multivalent ligands of the C-type lectin receptor DC-SIGN have emerged as effective antiadhesive agents against various pathogens. Some years ago, we described a hexavalent DC-SIGN ligand, Polyman-26, designed to bridge two of the four binding sites displayed by the receptor. In this work, we present our efforts to accomplish simultaneous coordination of all four carbohydrate binding sites of DC-SIGN through the synthesis of cross-shaped glycodendrimers. The tailored rigid scaffold allowed multivalent presentation of glycomimetics in a spatially defined fashion, while providing good water solubility to the constructs. Evaluation of the biological activity by SPR assays revealed strong binding avidity towards DC-SIGN and increased selectivity over langerin. Inhibition of DC-SIGN binding to SARS-CoV-2 spike protein and of DC-SIGN mediated Ebola virus trans-infection testifies for the glycodendrimers potential application in infection diseases. The tetravalent platform described here is easily accessible and can be used in modular fashion with different ligands, thus lending itself to multiple applications.
Carbohydrates; DC-SIGN; Dendrimers; Glycomimetics; Langerin
Settore CHIM/06 - Chimica Organica
H20MCITNIF15ABERN_M - Development of Selective Carbohydrate Immunomodulators Targeting C-type Lectin Receptors on Antigen Presenting Cells - BERNARDI, ANNA - H20MCITNIF - Horizon 2020_Marie Skłodowska-Curie actions-Innovative Training Network (ITN)/Individual Fellowships (IF) - 2015
29-apr-2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/933651
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