GdTI, the first thermostable trypsin inhibitor from Geoffroea decorticans seeds. A novel natural drug with potential application in biomedicine.

A novel thermostable trypsin inhibitor was obtained from Geoffroea decorticans seeds. G. decorticans trypsin inhibitor (GdTI) is a protein with molecular mass of 6743.7 Da, with a potent inhibitory activity (Ki of 2.1 nM) even at high temperatures and extreme pHs (100% after 5 h at 100 °C and 80% after 60 min at pH 2-12) constituting one of the most powerful serine protease inhibitors isolated from a plant source. GdTI displays anticoagulant activity against both extrinsic and intrinsic coagulation pathways, representing the first report of a plant serine protease inhibitor with anticoagulant activity against the extrinsic pathway. Finally, GdTI showed inhibitory activity against α-glucosidase (IC50 of 0.18 µM) evidencing the hypoglycemic effect of this inhibitor. Our results evidence the discovery of a natural molecule with unique features: i) GdTI is one of the most potent serine protease inhibitors founded to date, ii) with the most powerful thermostability reported in literature, iii) with anticoagulant effect against both coagulation pathways and hypoglycemic activity. This report suggest that GdTI could be exploited as a natural and hyperstable antidiabetic drug, in behalf of its antithrombotic and hypoglycemic activities, encouraging future studies with high impact on biomedical research and potential pharmaceutical applications.