Centro de Investigación de Proteínas Vegetales (CIPROVE), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de la Plata, 47 y 115s/N, B1900AVW La Plata, Buenos Aires, Argentina.
Centro de Investigación de Proteínas Vegetales (CIPROVE), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de la Plata, 47 y 115s/N, B1900AVW La Plata, Buenos Aires, Argentina.
Int J Biol Macromol. 2020 Apr 1;148:869-879. doi: 10.1016/j.ijbiomac.2020.01.214. Epub 2020 Jan 22.
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 (IC 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.
从 Geoffroea decorticans 种子中获得了一种新型热稳定的胰蛋白酶抑制剂。G. decorticans 胰蛋白酶抑制剂（GdTI）是一种分子量为 6743.7 Da 的蛋白质，具有很强的抑制活性（Ki 为 2.1 nM），即使在高温和极端 pH 值下（在 100°C 下 5 小时后保持 100%，在 pH 2-12 下 60 分钟后保持 80%），是从植物来源分离出的最强大的丝氨酸蛋白酶抑制剂之一。GdTI 对外源性和内源性凝血途径均具有抗凝活性，这是首次报道具有对外源性途径抗凝活性的植物丝氨酸蛋白酶抑制剂。最后，GdTI 对 α-葡萄糖苷酶表现出抑制活性（IC 为 0.18 μM），证明了该抑制剂的降血糖作用。我们的研究结果证实了一种具有独特特征的天然分子的发现：i）GdTI 是迄今为止发现的最有效的丝氨酸蛋白酶抑制剂之一，ii）具有文献中报道的最强热稳定性，iii）对两种凝血途径具有抗凝作用和降血糖活性。该报告表明，GdTI 可以作为一种天然的、超稳定的抗糖尿病药物被开发利用，因为其具有抗血栓形成和降血糖作用，鼓励未来进行对生物医学研究和潜在药物应用具有高影响力的研究。
