Nonhydrolyzable C-disaccharides, a new class of DC-SIGN ligands.
The discovery of effective ligands for DC-SIGN receptor is one of the most challenging concepts of antiviral drug design due to the importance of this C-type lectin in infection processes. DC-SIGN recognizes mannosylated and fucosylated oligosaccharides but glycosidic linkages are accessible to both chemical and enzymatic degradations. To avoid this problem, the synthesis of stable glycoside mimetics has attracted increasing attention. In this work we establish for the first time mono- and divalent C-glycosides based on d-manno and l-fuco configurations as prospective DC-SIGN ligands. In particular, the l-fucose glycomimetics were more active than the respective d-mannose ones. The highest affinity was assessed for simple 1,4-bis(α-l-fucopyranosyl)butane (SPR: IC500.43 mM) that displayed about twice higher activity than natural ligand Lex. Our results make C-glycosides attractive candidates for multivalent presentations.
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Benedetta
B
Bertolotti
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Beáta
B
Oroszová
University Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France; CNRS, IBS, F-38044, Grenoble, France; CEA, IBS, F-38044 Grenoble, France.
Ieva
I
Sutkeviciute
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Ladislav
L
Kniežo
University Grenoble Alpes, Institut de Biologie Structurale, F-38044 Grenoble, France; CNRS, IBS, F-38044, Grenoble, France; CEA, IBS, F-38044 Grenoble, France.
Franck
F
Fieschi
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Kamil
K
Parkan
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Zuzana
Z
Lovyová
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic.
Martina
M
Kašáková
Department of Chemistry of Natural Compounds, University of Chemistry and Technology, Technická 5, 166 28 Prague, Czech Republic. Electronic address: Jitka.Moravcova@vscht.cz.
Jitka
J
Moravcová
D032701:Biomimetics; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D005643:Fucose / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism*; D008358:Mannose / Q000737:chemistry; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D005643:Fucose; D006027:Glycosides; D037181:Lectins, C-Type; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
C-Disaccharides; DC-SIGN ligands; Glycomimetics; Surface plasmon resonance