1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and antiviral activity.
The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.
Reina
José J
JJ
Departamento de Química Bioorgánica, Instituto de Investigaciones Químicas, CSIC, Américo Vespucio 49, 41092 Sevilla, Spain.
Sattin
Sara
S
Invernizzi
Donatella
D
Mari
Silvia
S
Martínez-Prats
Lorena
L
Tabarani
Georges
G
Fieschi
Franck
F
Delgado
Rafael
R
Nieto
Pedro M
PM
Rojo
Javier
J
Bernardi
Anna
A
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D037181:Lectins, C-Type / Q000737:chemistry*; D008351:Mannans / Q000737:chemistry* / Q000494:pharmacology*; D018716:Molecular Mimicry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011956:Receptors, Cell Surface / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000998:Antiviral Agents; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C014647:mannobiose