Mallik Suman, Prasad Ramesh, Bhattacharya Anindita, Sen Prosenjit
Department of Biological Chemistry, Indian Association for the Cultivation of Science, 2A & 2B Raja S. C. Mullick Road, Jadavpur, Kolkata-700032, India.
ACS Med Chem Lett. 2018 Apr 12;9(5):434-439. doi: 10.1021/acsmedchemlett.8b00008. eCollection 2018 May 10.
Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.
天然磷脂酰丝氨酸(PS)含有两个手性中心,可增强血液凝固。然而,PS增强血液凝固的过程尚未完全了解。现已开发出一种高效且灵活的合成路线来合成PS的所有可能立体异构体。在本研究中,我们研究了PS手性中心在调节组织因子(TF)-因子VIIa凝血起始复合物活性中的作用。全长TF用磷脂酰胆碱重新脂质化,合成的PS异构体分别用于通过FXa生成试验评估TF-FVIIa复合物的促凝血活性。结果表明,起始复合物活性具有立体选择性,并且由于最佳的蛋白质-脂质相互作用,对PS甘油主链的构型具有更高的敏感性。