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 beta-eliminative depolymerization of FCS was developed by treating FCS benzyl esters with alkaline in anhydrous solution. Our results demonstrated that the glycosidic linkages of GaINAc-beta 1,4-GlcA were selectively cleaved and distinctive Delta(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 M-w 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. (C) 2015 Elsevier Ltd. All rights reserved.
Yunnan Provincial Science and Technology Department in China [2010CI116, 2012FB177, 2013FA046]
; National Natural Science Foundation of China [81102372, 81373292]
; Outstanding Technical Talent Foundation of the Chinese Academy of Sciences
; West Light Foundation of the Chinese Academy of Sciences
1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650201, Yunnan, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Dali Univ, Coll Pharm & Chem, Dali, Peoples R China 4.Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510275, Guangdong, Peoples R China