End-point modification of recombinant thrombomodulin with enhanced stability and anticoagulant activity.

ABSTRACT: Thrombomodulin (TM) is an endothelial cell membrane protein that plays essential roles in controlling vascular haemostatic balance. The 4, 5, 6 EGF-like domain of TM (TM₄₅₆) has cofactor activity for thrombin binding and subsequently protein C activation. Therefore, recombinant TM₄₅₆ is a promising anticoagulant candidate but has a very short half-life. Ligation of poly (ethylene glycol) to a bioactive protein (PEGylation) is a practical choice to improve stability, extend circulating life, and reduce immunogenicity of the protein. Site-specific PEGylation is preferred as it could avoid the loss of protein activity resulting from nonspecific modification. We report herein two site-specific PEGylation strategies, enzymatic ligation and copper-free click chemistry (CFCC

SUBMITTER: Liu X 

PROVIDER: S-EPMC6767613 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature