Targeting recombinant thrombomodulin fusion protein to red blood cells provides multifaceted thromboprophylaxis.

ABSTRACT: Thrombin generates fibrin and activates platelets and endothelium, causing thrombosis and inflammation. Endothelial thrombomodulin (TM) changes thrombin's substrate specificity toward cleavage of plasma protein C into activated protein C (APC), which opposes its thrombotic and inflammatory activities. Endogenous TM activity is suppressed in pathologic conditions, and antithrombotic interventions involving soluble TM are limited by rapid blood clearance. To overcome this problem, we fused TM with a single chain fragment (scFv) of an antibody targeted to red blood cells. scFv/TM catalyzes thrombin-mediated generation of activated protein C and binds to circulating RBCs without apparent damage, thereby prolonging its circulation time and bioavailability orders of magnitude compared with solub

SUBMITTER: Zaitsev S 

PROVIDER: S-EPMC3367878 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature