Study on the activity of recombinant mutant tissue-type plasminogen activator fused with the C-terminal fragment of hirudin.
J Thromb Thrombolysis
; 52(3): 880-888, 2021 Oct.
Article
em En
| MEDLINE
| ID: mdl-33826053
ABSTRACT
In the present study, bifunctional fusion proteins were designed by fusing the kringle 2 and protease domains of tissue-type plasminogen activator (tPA) to the C-terminal fragment of hirudin. The thrombolytic and anticoagulant activities of these recombinant proteins from mammalian cells were investigated using in vitro coagulation models and chromogenic assays. The results showed that all assayed tPA mutants retained catalytic activity. The C-terminal fragment of hirudin may have weak affinity to thrombin and thus was insufficient to suppress thrombin-mediated fibrin agglutination. The strength of the thrombolytic activity only relied on the selected tPA sequences, and the fibrinolytic efficiency of single-chain protein significantly decreased. Our data indicate that truncated tPA combined with a hirudin peptide may provide a framework for the further development of a new antithrombotic agent.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hirudinas
/
Ativador de Plasminogênio Tecidual
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article