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

COTABARREN, JULIANA; BROITMAN, DAIANA JUDITH; QUIROGA, EVELINA; OBREGÓN, WALTER DAVID

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

ELSEVIER SCIENCE BV

Año: 2020 vol. 148 p. 869 - 879

0141-8130

A novel thermostable trypsin inhibitorwas obtained fromGeoffroea 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 activityagainst 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 themost 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 studieswith high impact on biomedical research and potential pharmaceutical applications.