title: Insights into molecular recognition of Lewis(X) mimics by DC-SIGN using NMR and molecular modelling.
abstract: In this work, we have studied in detail the binding of two α-fucosylamide-based mimics of Lewis(X) to DC-SIGN ECD (ECD = extracellular domain) using STD NMR and docking. We have concluded that the binding mode occurs mainly through the fucose moiety, in the same way as Lewis(X). Similarly to other mimics containing mannose or fucose previously studied, we have shown that both compounds bind to DC-SIGN ECD in a multimodal fashion. In this case, the main contact is the interaction of two hydroxyl groups one equatorial and the other one axial (O3 and O4) of the fucose with the Ca(2+) as Lewis(X) and similarly to mannose-containing mimics (in this case the interacting groups are both in the equatorial position). Finally, we have measured the K(D) of one mimic that was 0.4 mM. Competitive STD NMR experiments indicate that the aromatic moiety provides additional binding contacts that increase the affinity.
authors: Glycosystems Laboratory, Instituto de Investigaciones Químicas, CSIC-US, AmericoVespucio, 49 41092 Sevilla, Spain.
authors: Cinzia
authors: C
authors: Guzzi
authors: Jesús
authors: J
authors: Angulo
authors: Fabio
authors: F
authors: Doro
authors: José J
authors: JJ
authors: Reina
authors: Michel
authors: M
authors: Thépaut
authors: Franck
authors: F
authors: Fieschi
authors: Anna
authors: A
authors: Bernardi
authors: Javier
authors: J
authors: Rojo
authors: Pedro M
authors: PM
authors: Nieto
mesh_terms: D001665:Binding Sites; D032701:Biomimetics / Q000379:methods*; D002236:Carbohydrate Conformation; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D003713:Dendritic Cells / Q000737:chemistry* / Q000276:immunology; D005643:Fucose / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007700:Kinetics; D037181:Lectins, C-Type / Q000737:chemistry* / Q000378:metabolism; D016256:Lewis X Antigen / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D005643:Fucose; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D008358:Mannose; D011956:Receptors, Cell Surface; D054852:Small Molecule Libraries; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin