Humanized Protein May Allow Anti-Thrombotic Screening
Protein affects hemostasis and thrombosis by binding to platelet receptors
MONDAY, Jan. 7 (HealthDay News) -- Modifying the mouse version of a protein that affects hemostasis and thrombosis by binding to platelet receptors allows the protein to bind human platelet receptors and may be a platform to screen anti-thrombotic drugs, according to the results of a study published online Dec. 16 in Nature Biotechnology.
Jianchun Chen, from Columbia University Medical Center in New York City, and colleagues modified an electrostatic "hot-spot" in the mouse version of the A1 domain of von Willebrand factor (VWF-A1) to improve its binding to the human platelet receptor glycoprotein Ib alpha (GPIbα).
The researchers found that the binding specificity of the modified VWF-A1 changed from the mouse to human GPIbα. Mice engineered to produce the modified VWF-A1 had a bleeding phenotype that was corrected by an infusion of human platelets, which formed occlusive thrombi.
"Thus, by modifying a protein interface, we have generated a potential biological platform for pre-clinical screening of anti-thrombotics that specifically target human platelets," Chen and colleagues conclude.