Mannose glycoconjugates functionalized at positions 1 and 6. Binding analysis to DC-SIGN using biosensors.
The design of glycoconjugates to allow the generation of multivalent ligands capable of interacting with the receptor DC-SIGN is a topic of high interest due to the role played by this lectin in pathogen infections. Mannose, a ligand of this lectin, could be conjugated at two different positions, 1 and 6, not implicated in the binding process. We have prepared mannose conjugates at these two positions with a long spacer to allow their attachment to a biosensor chip surface. Analysis of the interaction between these surfaces and the tetravalent extracellular domain (ECD) of DC-SIGN by SPR biosensor has demonstrated that both positions are available for this conjugation without affecting the protein binding process. These results emphasize the possibility to conjugate mannose at position 6, allowing the incorporation of hydrophobic groups at the anomeric position to interact with hydrophobic residues in the carbohydrate recognition domain of DC-SIGN, increasing binding affinities. This fact is relevant for the future design of new ligands and the corresponding multivalent systems for DC-SIGN.
Reina
José J
JJ
Grupo de Carbohidratos, Instituto de Investigaciones Químicas, CSIC, Américo Vespucio 49, E-41092 Sevilla, Spain.
Maldonado
Olivia S
OS
Tabarani
Georges
G
Fieschi
Franck
F
Rojo
Javier
J
D015374:Biosensing Techniques; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry*; D008320:Maltose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D008358:Mannose / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D006001:Glycoconjugates; D037181:Lectins, C-Type; D008320:Maltose; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C522263:2-((13-amino-4,7,10-trioxatridecylamino)succinamido)ethyl maltopyranoside; C522264:6-O-(2-((13-amino-4,7,10-trioxatridecylamino)succinamido)ethyl)maltopyranose