Study on the activity of recombinant mutant tissue-type plasminogen activator fused with the C-terminal fragment of hirudin
Research article published in Journal of thrombosis and thrombolysis (2021)
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.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Резюме
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.
Почему это важно для гирудотерапии
This study engineered bifunctional fusion proteins combining the kringle 2 and protease domains of tissue-type plasminogen activator with the C-terminal fragment of hirudin, testing their thrombolytic and anticoagulant activities in in-vitro coagulation models and chromogenic assays. The retained tPA catalytic activity was confirmed, but the hirudin C-terminal fragment showed only weak thrombin affinity and was insufficient to suppress fibrin agglutination, though the authors propose the framework could guide future antithrombotic agent development. This is directly relevant to ASH's domain as it explicitly leverages a hirudin-derived peptide in rational drug design. The work is preclinical and in-vitro only, and the hirudin fragment's contribution to anticoagulant activity was limited.
Цитирование
Study on the activity of recombinant mutant tissue-type plasminogen activator fused with the C-terminal fragment of hirudin
Ren K et al. · Journal of thrombosis and thrombolysis, 2021
Связанный клинический контекст
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