一种高效抗凝候选物：磺达肝癸钠类似物Rrt1.17的表征、合成及体内研究
An efficient anticoagulant candidate: Characterization, synthesis and in vivo study of a fondaparinux analogue Rrt1.17.
作者信息
Zhang Guo-Qiang, Jin Hongzhen, Zhao Yunyan, Guo Lina, Gao Xue, Wang Xiaoxue, Tie Shiyang, Shen Jie, Wang Peng George, Gan Hao, Cui Huifei, Zhao Wei
机构信息
The State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, People's Republic of China.
Institute of Biochemical and Biotech Drug, School of Pharmaceutical Sciences, Shandog Univeristy, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, People's Republic of China.
出版信息
Eur J Med Chem. 2017 Jan 27;126:1039-1055. doi: 10.1016/j.ejmech.2016.12.004. Epub 2016 Dec 2.
Fondaparinux, a synthetic pentasaccharide anticoagulant based on heparin antithrombin-binding domain, is derived from a chemical synthesis with more than 50 steps. Herein, we identified nine analogues separated from commercially available crude fondaparinux sodium, and tested their anticoagulant activity in vitro. Based on the activity results, the most active derivative Rrt1.17 was chemically synthesized. Biological properties in vitro and in vivo indicated that the well-defined derivative Rrt1.17 was a more efficient anticoagulant candidate compared with fondaparinux.
磺达肝癸钠是一种基于肝素抗凝血酶结合域的合成五糖抗凝剂，由超过50步的化学合成得到。在此，我们从市售的粗制磺达肝癸钠中分离出9种类似物，并在体外测试了它们的抗凝活性。根据活性结果，化学合成了活性最高的衍生物Rrt1.17。体外和体内生物学特性表明，与磺达肝癸钠相比，结构明确的衍生物Rrt1.17是一种更有效的抗凝候选物。
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