Kotar Anita, Tomašič Tihomir, Lenarčič Živković Martina, Jug Gregor, Plavec Janez, Anderluh Marko
Slovenian NMR center, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
Org Biomol Chem. 2016 Jan 21;14(3):862-75. doi: 10.1039/c5ob01916h. Epub 2015 Nov 18.
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.
利用高分辨率核磁共振结合分子模拟研究基于甘露糖的配体与受体DC-SIGN的相互作用，结果表明，四种α-D-甘露糖苷配体主要通过甘露糖部分与结合位点相互作用。通过甘油连接体与α-D-甘露糖相连的另外两个芳香基团表现出的相互作用可能与其取代模式有关。具有萘基和间位取代苯环的配体表现出最有利的结合特性。除了预测的芳香基团疏水相互作用外，我们的结果还提出了取代苯部分在DC-SIGN扁平结合位点极性更强区域的新接触方式，从而为进一步设计新型、更有效的DC-SIGN拮抗剂提供了新的可能性。
