Thrombin is a crucial regulatory serine protease in hemostasis and thrombosis and has been a therapeutic target of thrombotic events. A novel oyster-derived thrombin inhibitory dodecapeptide (IEELEELEAER, P-2-CG) was identified and characterized. P-2-CG prolonged thrombin time from 9.6 s to 23.3 s at 5 mg/mL in vitro. P-2-CG bound to thrombin Exosite-I domain spontaneously. The occupied Exosite-I blocked fibrinogen binding, which prolonged fibrinogen clotting time to 28 s from 18.5 s. Molecule dynamics demonstrated the interaction of P-2-CG and thrombin Exosite-I involved in eight hydrogen bonds and lots of electrostatic forces. The residue Tyr76 at thrombin Exosite-I is one critical amino acid for fibrinogen binding. The Glu11 in P-2-CG was bound with Tyr76 through strong hydrogen bonds and hydrophobic action. P-2-CG also significantly reduced the mortality of mice that suffered an acute pulmonary embolism induced by thrombin and inhibited mice tail thrombosis induced by κ-carrageenan. The thrombin inhibitory efficiency in vitro and antithrombosis in vivo of P-2-CG provided insight for further applications to serve as an antithrombotic agent.

Anticoagulant Dodecapeptide Suppresses Thrombosis in Vivo by Inhibiting the Thrombin Exosite-I Binding Site / Cheng, S.; Wang, Y.; Chen, H.; Liu, H.; Wang, L.; Battino, M.; Yao, X.; Zhu, B.; Du, M.. - In: JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY. - ISSN 0021-8561. - ELETTRONICO. - 69:37(2021), pp. 10920-10931. [10.1021/acs.jafc.1c03414]

Anticoagulant Dodecapeptide Suppresses Thrombosis in Vivo by Inhibiting the Thrombin Exosite-I Binding Site

Battino M.
Supervision
;
2021-01-01

Abstract

Thrombin is a crucial regulatory serine protease in hemostasis and thrombosis and has been a therapeutic target of thrombotic events. A novel oyster-derived thrombin inhibitory dodecapeptide (IEELEELEAER, P-2-CG) was identified and characterized. P-2-CG prolonged thrombin time from 9.6 s to 23.3 s at 5 mg/mL in vitro. P-2-CG bound to thrombin Exosite-I domain spontaneously. The occupied Exosite-I blocked fibrinogen binding, which prolonged fibrinogen clotting time to 28 s from 18.5 s. Molecule dynamics demonstrated the interaction of P-2-CG and thrombin Exosite-I involved in eight hydrogen bonds and lots of electrostatic forces. The residue Tyr76 at thrombin Exosite-I is one critical amino acid for fibrinogen binding. The Glu11 in P-2-CG was bound with Tyr76 through strong hydrogen bonds and hydrophobic action. P-2-CG also significantly reduced the mortality of mice that suffered an acute pulmonary embolism induced by thrombin and inhibited mice tail thrombosis induced by κ-carrageenan. The thrombin inhibitory efficiency in vitro and antithrombosis in vivo of P-2-CG provided insight for further applications to serve as an antithrombotic agent.
2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11566/297658
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