title: STD NMR and molecular modelling insights into interaction of novel mannose-based ligands with DC-SIGN.
abstract: Study of interaction of mannose-based ligands with receptor DC-SIGN using high resolution NMR in combination with molecular modelling showed that four α-d-mannoside ligands interact with the binding site predominantly through the mannose moiety. The other two aromatic groups that are bound to α-d-mannose through a glycerol linker demonstrate interaction that can be related to their substitution pattern. Ligand with naphthyl and meta-substituted phenyl ring exhibited the most favourable binding characteristics. In addition to the predicted hydrophobic interactions of aromatic moieties our results propose new contacts of substituted phenyl moiety in the more polar area of the flat binding site of DC-SIGN and thus offer new possibilities in further designing of novel, more potent DC-SIGN antagonists.
authors.affiliation: Slovenian NMR center, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia. janez.plavec@ki.si.
authors.forename: Anita
authors.initials: A
authors.lastname: Kotar
authors.forename: Tihomir
authors.initials: T
authors.lastname: Tomašič
authors.forename: Martina
authors.initials: M
authors.lastname: Lenarčič Živković
authors.forename: Gregor
authors.initials: G
authors.lastname: Jug
authors.forename: Janez
authors.initials: J
authors.lastname: Plavec
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
mesh_terms: D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008358:Mannose / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin