中国生物工程杂志

Objective: The venom glands of toxic animals secrete a large number of structurally diverse and functionally rich active peptides, representing a natural treasure trove for peptide drug development. At present, only a small portion of the active peptides from toxic animals have been studied, so there is a need to establish a more efficient method of active peptide discovery. Methods: The anticoagulant peptides were developed by transcriptome sequencing, data analysis and polypeptide selection, peptide preparation by recombinant expression, in vitro activity screening, and in vivo activity evaluation in animal models of the Draconarius digitusiformis. Results: PDBPE-001, an inhibitor of coagulation Factor Xa, was screened. The peptide has a molecular weight of 9 889.82 Da, consisting of 92 amino acid residues and 4 pairs of disulfide bonds. This peptide can be efficiently prepared through recombinant expression, and its inhibitory activity against Factor Xa is concentration dependent, with an IC₅₀ ~ 0.807 μmol/L. In the mouse thrombus model, 30 mg/kg of PDBPE-001 has a good anti-thrombotic effect. Conclusions: A novel Factor Xa inhibitor has been obtained for the first time from the Draconarius digitusiformis, providing a new lead peptide molecule for the development of new anticoagulants.