Abstract Number: PB0069
Meeting: ISTH 2021 Congress
Background: Para-sulfonato-calix[n]arenes (CnS) are capable of complexing biologically active molecules. The CnS hydrophobic core and anionic rim can facilitate protein recognition by capturing the arginine or lysine side chains. The potential bioactivity of CnS derivatives in relation to some components of the hemostatic system has been shown.
Aims: In this work, the influence of C4S (rigid cone structure) and C6S (flexible double partial cone structure) on the coagulation system components was studied.
Methods: C4S and C6S effect on thrombin and Xa-factor, plasma overall haemostatic potential (OHP), prothrombin time, APTT, Z-potential and fluorescent spectrum of fibrinogen (Fg), and Fg coagulation by thrombin were studied.
Results: C6S was a stronger noncompetitive inhibitor of thrombin (Ki = 0.27 mM) than C4S (Ki = 1.1 mM). C4S and C6S decreased Xa activity. C4S had little effect on plasma OHP, C6S increased the lag phase and reduced the amount of fibrin formed. C4S had no effect, C6S significantly increased prothrombin time and APTT. C4S and C6S form complexes with Fg and change its conformation: the fluorescence quenching constants are 1.3*104 and 1.1*104 M-1, respectively. Analysis of the Z-potential showed C6S increasing the negative charge of Fg stronglier than C4S. C4S reduced the lag phase and increased the rate of Fg clotting by thrombin, while C6S (> 100 μM) increased the lag phase and decreased the amount of fibrin until the complete suppression of Fg clotting.
Conclusions: The differences between C4S and C6S are related to their structure, flexibility and the number of negative charges. C4S stimulates the clotting of fibrinogen, mainly by a change in the protein conformation upon complexation with a rigid C4S structure. C6S inhibits Fg coagulation due to strong inhibition of thrombin activity and influence on the coagulation factors cascade. Innocuous C4S may be promising for stopping local bleeding.
(Funds of the State Registration topic no. AAA-A16-116052010081-5)
To cite this abstract in AMA style:Ivanova E, Aisina R, Gershkovich K. Influence of Para-sulfonato-calixarenes on Components of Coagulation System [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/influence-of-para-sulfonato-calixarenes-on-components-of-coagulation-system/. Accessed September 16, 2021.
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