Production and functional characteristics of a novel hirudin variant with better anticoagulant activities than bivalirudin
Research article published in Journal of enzyme inhibition and medicinal chemistry (2025)
Abstract
Current antithrombotic therapies face dual constraints of bleeding complications and monitoring requirements. Although natural hirudin provides targeted thrombin inhibition, its clinical adoption is hindered by sourcing limitations. This study developed a recombinant hirudin variant HMg (rHMg) with enhanced anticoagulant activity through genetic engineering and established cost-effective large-scale production methods. The synthesised HMg gene was expressed in E. coli BL21 via a pET vector plasmid, followed by nickel-affinity purification. Systematic evaluations demonstrated rHMg's antithrombin activity of 9573 ATU/mg, dose-dependent prolongation of APTT/PT/TT. It has superior thrombin inhibition with the IC50 and Ki values were 2.8 and 0.323 nM respectively compared to FDA approved drug bivalirudin (p < 0.001). The high-yield prokaryotic expression of rHMg with enhanced anticoagulant efficacy provides a novel strategy for developing affordable antithrombotic drugs, showing significant potential for cardiovascular disease management.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Production and functional characteristics of a novel hirudin variant with better anticoagulant activities than bivalirudin.
Why This Matters for Hirudotherapy
This study reports the development of a recombinant hirudin variant, rHMg, with enhanced anticoagulant activity relative to bivalirudin, produced via E. coli expression and nickel-affinity purification. The abstract states that rHMg exhibited antithrombin activity of 9573 ATU/mg, dose-dependent prolongation of APTT/PT/TT, and superior thrombin inhibition with IC50 and Ki values of 2.8 and 0.323 nM, respectively, compared to bivalirudin. The authors frame this as a strategy for affordable antithrombotic drug development. The topic is relevant to hirudotherapy insofar as the starting point is natural hirudin, but the abstract does not specify its biological source and the work concerns a synthesized recombinant protein rather than live leeches. Findings would require further validation beyond the reported evaluations.
Citation
Production and functional characteristics of a novel hirudin variant with better anticoagulant activities than bivalirudin
Ge L et al. · Journal of enzyme inhibition and medicinal chemistry, 2025
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