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Synthesis of Novel DC‐SIGN Ligands with an α‐Fucosylamide Anchor
Author(s) -
Timpano Gabriele,
Tabarani Georges,
Anderluh Marko,
Invernizzi Donatella,
Vasile Francesca,
Potenza Donatella,
Nieto Pedro M.,
Rojo Javier,
Fieschi Franck,
Bernardi Anna
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800139
Subject(s) - dc sign , fucose , chemistry , stereochemistry , adhesion , functional diversity , receptor , c type lectin , lectin , biophysics , dendritic cell , glycoprotein , biochemistry , biology , antigen , immunology , ecology , organic chemistry
The dendritic cell‐specific intercellular adhesion molecule (ICAM) 3‐grabbing nonintegrin (DC‐SIGN) is a C‐type lectin that appears to perform several different functions. Besides mediating adhesion between dendritic cells and T lymphocytes, DC‐SIGN recognizes several pathogens some of which, including HIV, appear to exploit it to invade host organisms. The intriguing diversity of the roles attributed to DC‐SIGN and their therapeutic implications have stimulated the search for new ligands that could be used as biological probes and possibly as lead compounds for drug development. The natural ligands of DC‐SIGN consist of mannose oligosaccharides or fucose‐containing Lewis‐type determinants. Using the known 3D structure of the Lewis‐x trisaccharide, we have identified some monovalent α‐fucosylamides that bind to DC‐SIGN with inhibitory constants 0.4–0.5 m M , as determined by SPR, and have characterized their interaction with the protein by STD NMR spectroscopy. This work establishes for the first time α‐fucosylamides as functional mimics of chemically and enzymatically unstable α‐fucosides and describes interesting candidates for the preparation of multivalent systems able to block the receptor DC‐SIGN with high affinity and with potential biomedical applications.