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目的:利用重组血管内皮细胞生长因子(VEGF)受体1激酶蛋白质建立大规模随机筛选分子模型.方法:重组人源VEGF受体1激酶蛋白质的催化活性通过酶联免疫法检测96孔板上的底物磷酸化程度得到.用大规模随机筛选寻找抑制剂,并在稳定表达VEGF受体1的细胞系上研究它们的性质.结果:在研究VEGF受体1激酶蛋白质大肠杆菌表达体系的基础上,建立了大规模筛选模型.通过对2800个有机化合物的筛选,找到了两个二取代呋喃类的VEGF受体1激酶抑制剂(A1和A5).其中化合物A1能抑制底物磷酸化,而化合物A5则对激酶的自磷酸化和底物磷酸化都能抑制.同时A1和A5都能影响转染细胞上的受体磷酸化作用.结论:利用重组受体激酶建立的分子模型为寻找抗肿瘤血管生成抑制剂提供了一个简单而有效的方法.
OBJECTIVE: To establish a large-scale random screening molecular model using recombinant human vascular endothelial growth factor (VEGF) receptor 1 kinase protein.Methods: The catalytic activity of recombinant human VEGF receptor 1 kinase protein was detected by enzyme-linked immunosorbent assay Substance phosphorylation was obtained.Screening inhibitors with a large randomized screen and investigating their properties on cell lines stably expressing VEGF receptor 1. Results: On the basis of studying the expression system of the VEGF receptor 1 kinase protein Escherichia coli , A large-scale screening model was established.After screening 2,800 organic compounds, two disubstituted furofuranosyl-1-kinase inhibitors (A1 and A5) were found, of which compound A1 inhibited substrate phosphorylation Compound A5 inhibited both autophosphorylation and phosphorylation of kinases, and both A1 and A5 inhibited the phosphorylation of receptors on transfected cells.Conclusion: The molecular model established by recombinant receptor kinases Tumor angiogenesis inhibitors provide a simple and effective method.