Acyclic Tethers Mimicking Subunits of Polysaccharide Ligands: Selectin Antagonists
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- 作者：Mickael Calosso ; Guillaume Tambutet ; Daniel Charpentier ; Gabrielle St-Pierre ; Marc Vaillancourt ; Mohammed Bencheqroun ; Jean-Philippe Gratton ; Michel Pr茅vost ; Yvan Guindon
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2014
- 出版时间：September 11, 2014
- 年：2014
- 卷：5
- 期：9
- 页码：1054-1059
- 全文大小：440K
- ISSN：1948-5875
文摘
We report on the design and synthesis of molecules having E- and P-selectins blocking activity both in vitro and in vivo. The GlcNAc component of the selectin ligand sialyl LewisX was replaced by an acyclic tether that links two saccharide units. The minimization of intramolecular dipole鈥揹ipole interactions and the gauche effect would be at the origin of the conformational bias imposed by this acyclic tether. The stereoselective synthesis of these molecules, their biochemical and biological evaluations using surface plasmon resonance spectroscopy (SPR), and in vivo assays are described. Because the structure of our analogues differs from the most potent E-selectin antagonists reported, our acyclic analogues offer new opportunities for chemical diversity.