title: An efficient anticoagulant candidate: Characterization, synthesis and in vivo study of a fondaparinux analogue Rrt1.17.
abstract: 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.
authors.affiliation: 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.
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Hongzhen
authors.initials: H
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Lina
authors.initials: L
authors.lastname: Guo
authors.affiliation: Institute of Biochemical and Biotech Drug, School of Pharmaceutical Sciences, Shandog Univeristy, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Gao
authors.affiliation: Institute of Biochemical and Biotech Drug, School of Pharmaceutical Sciences, Shandog Univeristy, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, People's Republic of China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Biochemical and Biotech Drug, School of Pharmaceutical Sciences, Shandog Univeristy, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, People's Republic of China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Tie
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: 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.
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
authors.affiliation: Business School of Nankai University, 94 Weijin Road, Tianjin 300071, People's Republic of China. Electronic address: create_0730@163.com.
authors.forename: Hao
authors.initials: H
authors.lastname: Gan
authors.affiliation: Institute of Biochemical and Biotech Drug, School of Pharmaceutical Sciences, Shandog Univeristy, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, People's Republic of China. Electronic address: cuihuifei@sdu.edu.cn.
authors.forename: Huifei
authors.initials: H
authors.lastname: Cui
authors.affiliation: 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. Electronic address: wzhao@nankai.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D000077425:Fondaparinux; D020128:Inhibitory Concentration 50; D011134:Polysaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000991:Antithrombins; D011134:Polysaccharides; D000077425:Fondaparinux
keywords: Anticoagulant activity; Fondaparinux analogues; Structure-activity relationships; Synthesis