title: β-Eliminative depolymerization of the fucosylated chondroitin sulfate and anticoagulant activities of resulting fragments.
abstract: Fucosylated chondroitin sulfate (FCS) from sea cucumber with complex structure has potent anticoagulant activity by inhibition of intrinsic tenase; however, it could activate factor XII and platelet. To obtain FCS' fragments with selective inhibition on intrinsic tenase, a method for β-eliminative depolymerization of FCS was developed by treating FCS benzyl esters with alkaline in anhydrous solution. Our results demonstrated that the glycosidic linkages of GalNAc-β1, 4-GlcA were selectively cleaved and distinctive Δ(4,5) unsaturated hexuronic acid was formed at non-reducing end of resulting fragments, while the main structures were essentially stable during depolymerization. By this method, five depolymerized fragments (dFCSs) with various molecular sizes were prepared and their anticoagulant activities and activation activities of factor XII and platelet were compared. Overall, dFCSs with Mw 3.2-8.8 kDa reserved potent anticoagulant activities by inhibition of intrinsic tenase, and activation activities of factor XII or platelet could be diminished or eliminated.
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China; University of Chinese Academy of Sciences, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: College of Pharmacy and Chemistry, Dali University, Dali, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Chuang
authors.initials: C
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.
authors.forename: Mingyi
authors.initials: M
authors.lastname: Wu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Jiang
authors.affiliation: College of Pharmacy and Chemistry, Dali University, Dali, China. Electronic address: lgm13330555378@126.com.
authors.forename: Guangming
authors.initials: G
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. Electronic address: zhao.jinhua@yahoo.com.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Zhao
mesh_terms: D000925:Anticoagulants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000737:chemistry* / Q000494:pharmacology*; D005174:Factor XII / Q000037:antagonists & inhibitors*; D006801:Humans; D015394:Molecular Structure; D058105:Polymerization
chemical_list: D000925:Anticoagulants; C517150:fucosylated chondroitin sulfate; D005174:Factor XII; D002809:Chondroitin Sulfates
keywords: Anticoagulant; Benzyl esterification; Depolymerization; Fucosylated chondroitin sulfate; β-Elimination