Tags

Type your tag names separated by a space and hit enter

Anticoagulant Decapeptide Interacts with Thrombin at the Active Site and Exosite-I.
J Agric Food Chem 2020; 68(1):176-184JA

Abstract

Thrombin can be used as a target for its inhibitors to prevent blood coagulation. A novel peptide (TKLTEEEKNR, PfCN) identified from αS2-casein (fragments 211-220) with high anticoagulant activity was screened and prepared. The activated partial thromboplastin time, prothrombin time, and thrombin time, at the concentration of 4 mM, prolonged about 19, 2.5 and 5.5 s, respectively. At the same concentration, the fibrinogen clotting time prolonged from 25.5 ± 0.7 to 38.3 ± 1.3 s. The thrombin inhibitory efficiency in vitro (IC50 value of 29.27 mM) and antithrombosis effect in vivo were determined. The secondary structure of thrombin, which was influenced by PfCN, indicates that PfCN can bind to thrombin. Isothermal titration calorimetry and the chromogenic substrate test showed that PfCN belongs to the bivalent thrombin inhibitor like bivalirudin. Although the effect was not as good as bivalirudin, in the animal experiment, bleeding occurred in the bivalirudin group but not in the PfCN group. Moreover, molecular docking illustrates the mechanism for the antithrombin activity of PfCN. These results indicated that PfCN could be used as an effective thrombin inhibitor with broad potential for the prevention of thrombotic acute pulmonary embolism and other thrombotic events.

Authors+Show Affiliations

School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China.School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China.School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China. Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering , China Agricultural University , Beijing 100083 , China.School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China.School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China.School of Food Science and Technology, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing , Dalian Polytechnic University , Dalian 116034 , China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31850760

Citation

Liu, Hanxiong, et al. "Anticoagulant Decapeptide Interacts With Thrombin at the Active Site and Exosite-I." Journal of Agricultural and Food Chemistry, vol. 68, no. 1, 2020, pp. 176-184.
Liu H, Tu M, Cheng S, et al. Anticoagulant Decapeptide Interacts with Thrombin at the Active Site and Exosite-I. J Agric Food Chem. 2020;68(1):176-184.
Liu, H., Tu, M., Cheng, S., Xu, Z., Xu, X., & Du, M. (2020). Anticoagulant Decapeptide Interacts with Thrombin at the Active Site and Exosite-I. Journal of Agricultural and Food Chemistry, 68(1), pp. 176-184. doi:10.1021/acs.jafc.9b06450.
Liu H, et al. Anticoagulant Decapeptide Interacts With Thrombin at the Active Site and Exosite-I. J Agric Food Chem. 2020 Jan 8;68(1):176-184. PubMed PMID: 31850760.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anticoagulant Decapeptide Interacts with Thrombin at the Active Site and Exosite-I. AU - Liu,Hanxiong, AU - Tu,Maolin, AU - Cheng,ShuZhen, AU - Xu,Zhe, AU - Xu,Xianbing, AU - Du,Ming, Y1 - 2019/12/27/ PY - 2019/12/19/pubmed PY - 2020/1/28/medline PY - 2019/12/19/entrez KW - acute pulmonary embolism KW - antithrombosis KW - bivalent thrombin inhibitor KW - casein KW - molecule docking SP - 176 EP - 184 JF - Journal of agricultural and food chemistry JO - J. Agric. Food Chem. VL - 68 IS - 1 N2 - Thrombin can be used as a target for its inhibitors to prevent blood coagulation. A novel peptide (TKLTEEEKNR, PfCN) identified from αS2-casein (fragments 211-220) with high anticoagulant activity was screened and prepared. The activated partial thromboplastin time, prothrombin time, and thrombin time, at the concentration of 4 mM, prolonged about 19, 2.5 and 5.5 s, respectively. At the same concentration, the fibrinogen clotting time prolonged from 25.5 ± 0.7 to 38.3 ± 1.3 s. The thrombin inhibitory efficiency in vitro (IC50 value of 29.27 mM) and antithrombosis effect in vivo were determined. The secondary structure of thrombin, which was influenced by PfCN, indicates that PfCN can bind to thrombin. Isothermal titration calorimetry and the chromogenic substrate test showed that PfCN belongs to the bivalent thrombin inhibitor like bivalirudin. Although the effect was not as good as bivalirudin, in the animal experiment, bleeding occurred in the bivalirudin group but not in the PfCN group. Moreover, molecular docking illustrates the mechanism for the antithrombin activity of PfCN. These results indicated that PfCN could be used as an effective thrombin inhibitor with broad potential for the prevention of thrombotic acute pulmonary embolism and other thrombotic events. SN - 1520-5118 UR - https://www.unboundmedicine.com/medline/citation/31850760/Anticoagulant_Decapeptide_Interacts_with_Thrombin_at_the_Active_Site_and_Exosite-I L2 - https://dx.doi.org/10.1021/acs.jafc.9b06450 DB - PRIME DP - Unbound Medicine ER -