Allosterism-based simultaneous, dual anticoagulant and antiplatelet action: allosteric inhibitor targeting the glycoprotein Ibα-binding and heparin-binding site of thrombin.

ABSTRACT:

Background

Allosteric inhibition is a promising approach for developing a new group of anticoagulants with potentially reduced bleeding consequences. Recently, we designed sulfated β-O4 lignin (SbO4L) as an allosteric inhibitor that targets exosite 2 of thrombin to reduce fibrinogen cleavage through allostery and compete with glycoprotein Ibα to reduce platelet activation.

Objective

To assess: (i) the antithrombotic potential of a novel approach of simultaneous exosite 2-dependent allosteric inhibition of thrombin and competitive inhibition of platelet activation; and (ii) the promise of SbO4L as the first-in-class antithrombotic agent.

Methods

A combination of whole blood thromboelastography, hemostasis analysis, mouse arterial thrombosis models and mouse tail bleedi

SUBMITTER: Mehta AY 

PROVIDER: S-EPMC4828251 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature