Discovery of Anticoagulant Active Peptides from the Venom Glands of the Draconarius digitusiformis
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.
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