HIV-1整合酶(integrase,IN)是病毒复制过程的关键酶,已被证实是开发抗HIV-1药物的一个理想靶标。针对48个喹诺酮酸类整合酶链转移抑制剂(integrasestrandtransfer inhibitors, INSTIs),利用遗传函数逼近法(genetic function approximati...HIV-1整合酶(integrase,IN)是病毒复制过程的关键酶,已被证实是开发抗HIV-1药物的一个理想靶标。针对48个喹诺酮酸类整合酶链转移抑制剂(integrasestrandtransfer inhibitors, INSTIs),利用遗传函数逼近法(genetic function approximation, GFA)构建10个抑制活性与优选的分子结构描述符之间的二维定量构效关系(2D-QSAR)模型,从中优选出最佳的模型并对其进行验证,据此探究影响抑制剂生物活性的主要分子微观结构因素,希冀为其进一步结构优化提供理论指导。所建立的最优2D-QSAR模型的非交叉验证相关系数R^2为0.8903,交叉验证相关系数Q^2为0.8213,表明该模型具有较高的预测能力和明显的统计学意义。该研究表明,喹诺酮酸类INSTIs的生物活性主要受Jurs_RPCG、Shadow_nu、BIC、ALogP、Dipole_X以及Dipole_Y描述符的影响,为其进一步结构修饰,开发高效抗HIV-1药物奠定了理论基础。展开更多
To identify the inhibitor of glutathione S-transferase（GST）,a high-throughput screening method was established in a 384-well microplate with total 35 μL volume,and the absorbance at 340 nm is detected.The concentra...To identify the inhibitor of glutathione S-transferase（GST）,a high-throughput screening method was established in a 384-well microplate with total 35 μL volume,and the absorbance at 340 nm is detected.The concentrations of substrates,CDNB and GST were determined by chromatometry.The optimal enzyme kinetics reaction time and temperature are 2 h and 30 ℃,respectively.The established model was evaluated by NaOCl,a known GST inhibitor,and the parameter Z′ was 0.77,which showed a high feasibility and stability of the assay.A total of 31 098 compounds were screened,of which 4 compounds were shown to inhibit GST activity,high inhibiting activity for their IC50 of GST inhibition was 3.94,4.05,74.85,and 77.41 mg·L-1,separately.The results indicated that the colorimetric method by using CDNB and GSH as substrate is stable,sensitive,reproducible and also suitable for high throughput screening.展开更多
文摘To identify the inhibitor of glutathione S-transferase（GST）,a high-throughput screening method was established in a 384-well microplate with total 35 μL volume,and the absorbance at 340 nm is detected.The concentrations of substrates,CDNB and GST were determined by chromatometry.The optimal enzyme kinetics reaction time and temperature are 2 h and 30 ℃,respectively.The established model was evaluated by NaOCl,a known GST inhibitor,and the parameter Z′ was 0.77,which showed a high feasibility and stability of the assay.A total of 31 098 compounds were screened,of which 4 compounds were shown to inhibit GST activity,high inhibiting activity for their IC50 of GST inhibition was 3.94,4.05,74.85,and 77.41 mg·L-1,separately.The results indicated that the colorimetric method by using CDNB and GSH as substrate is stable,sensitive,reproducible and also suitable for high throughput screening.
