Issue 15, 2008

Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin

Abstract

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.

Graphical abstract: Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin

Supplementary files

Article information

Article type
Paper
Submitted
06 Feb 2008
Accepted
28 Apr 2008
First published
05 Jun 2008

Org. Biomol. Chem., 2008,6, 2743-2754

Docking, synthesis, and NMR studies of mannosyl trisaccharide ligands for DC-SIGN lectin

J. J. Reina, I. Díaz, P. M. Nieto, N. E. Campillo, J. A. Páez, G. Tabarani, F. Fieschi and J. Rojo, Org. Biomol. Chem., 2008, 6, 2743 DOI: 10.1039/B802144A

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