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计算机辅助设计FAPα酶激活式鬼臼毒素抗肿瘤前体药物分子
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Abstract:
为了获得成纤维细胞激活蛋白α (Fibroblast Activation Protein，简称FAPα酶)激活式鬼臼毒素抗肿瘤前体药物分子，利用AutoDock tools、PyMOL和Ligplot软件模块的功能，设计FAPα酶的特异性底物N-苄氧羰基甘氨酰-L-脯氨酸与鬼臼毒素4-OH偶联中间片段及最终化合物的结构。通过虚拟设计共获得31个Affinity(kcal/mol)评分值小于？9.5分的化合物，并阐明了5个最优代表的复合物模拟三维结构与分子互作机制，为FAPα酶激活式鬼臼毒素抗肿瘤药物研发提供潜在的先导化合物，以指导后期研究的进一步开展。
To obtain the anti-tumor prodrugs of FAPα-activated podophyllotoxin, the intermediate structure of N-benzyloxycarbonylglycine-L-proline coupling with podophyllotoxin was designed by using Auto-Dock tools, PyMOL and Ligplot software modules. A total of 31 compounds with affinity scores less than ？9.5 kcal/mol were obtained by virtual design, and the three-dimensional structure and mo-lecular interaction mechanism of five optimal representative complexes were clarified, which pro-vided potential lead compounds for the research and development of FAPα-activated anti-tumor prodrug of podophyllotoxin to guide the further research.
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