Abstract
Selective inhibition of the endogenous coagulation pathway is a promising strategy for developing new anticoagulants. Fucosylated glycosaminoglycan (FG), a structurally complex glycosaminoglycan, has distinct anticoagulant properties, especially the strong intrinsic factor Xase inhibitory activity that is recognized as a new target with potential physiological and therapeutic applications. Detailed knowledge of FG structures is necessary for developing a clinically effective intrinsic FXase inhibitor. However, challenges remain to elucidate FG structures as a basis for pharmaceutical development. Herein, using the highly selective β-elimination method, oligosaccharides with regular structures were prepared from the depolymerization products. Analysis of oligosaccharides further confirmed the precise structural sequence of the FG. Furthermore, biological activity assay suggested that these pure homogeneous oligosaccharides, particularly an octasaccharide, exhibit strong inhibition of the intrinsic coagulation pathway by inhibiting human intrinsic factor Xase. Our finding is significant for discovery of a new class of anticoagulant agents as intrinsic factor Xase inhibitors.
Citations
Jul 18, 2018·Glycobiology·Lisha LinJinhua Zhao
Aug 2, 2018·Angewandte Chemie·Xiao ZhangZhongjun Li
Jul 22, 2018·The Journal of Biological Chemistry·Ronghua YinJinhua Zhao
Jul 7, 2020·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Yuefan SongRobert J Linhardt
Jun 5, 2020·Marine Drugs·Giulia VessellaEmiliano Bedini
Sep 25, 2020·Platelets·Lisha LinJinhua Zhao
Apr 3, 2019·Marine Drugs·Wenqi ZhengJinhua Zhao
Apr 3, 2019·Marine Drugs·Ruowei GuanJinhua Zhao
Nov 27, 2019·Marine Drugs·Giulia VessellaEmiliano Bedini
Jul 20, 2019·Carbohydrate Polymers·Lufeng YanShiguo Chen
Sep 2, 2019·Carbohydrate Polymers·Ying CaiJinhua Zhao
Feb 16, 2020·Carbohydrate Polymers·Wenjiao YangJinhua Zhao
Feb 23, 2021·Biomacromolecules·Ronghua YinJinhua Zhao
Jul 29, 2020·Carbohydrate Polymers·Hui MaoJinhua Zhao
Aug 25, 2020·International Journal of Biological Macromolecules·Na GaoJinhua Zhao
Nov 5, 2020·Carbohydrate Polymers·Hong LiLongyan Zhao
Sep 18, 2020·European Journal of Medicinal Chemistry·Huifang SunJinhua Zhao
Apr 4, 2021·Marine Drugs·Xiang ShiJinhua Zhao
Jul 24, 2021·Carbohydrate Polymers·Shanni LiJinhua Zhao
Jul 12, 2021·International Journal of Biological Macromolecules·Yan MaJinhua Zhao
Aug 9, 2021·Carbohydrate Polymers·Ru ChenJinhua Zhao
Nov 16, 2021·Biomacromolecules·Giulia VessellaEmiliano Bedini