Identification of a small molecule that modulates platelet glycoprotein Ib-von Willebrand factor interaction.

ABSTRACT: The von Willebrand factor (VWF) A1-glycoprotein (GP) Ibα interaction is of major importance during thrombosis mainly at sites of high shear stress. Inhibitors of this interaction prevent platelet-dependent thrombus formation in vivo, without major bleeding complications. However, the size and/or protein nature of the inhibitors currently in development limit oral bioavailability and clinical development. We therefore aimed to search for a small molecule protein-protein interaction inhibitor interfering with the VWF-GPIbα binding. After determination of putative small molecule binding pockets on the surface of VWF-A1 and GPIbα using site-finding algorithms and molecular dynamics, high throughput molecular docking was performed on both binding partners. A selection of compounds showing good

SUBMITTER: Broos K 

PROVIDER: S-EPMC3308782 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature