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以往研究对 34个针对蛋白激酶 C- α m RNA二级结构设计的反义药物 (AS- ODNs)进行了定量构效关系 (QSAR)分析并得到 QSAR方程 .本研究再次设计 1 0个 AS- ODNs验证 QSAR方程对药物活性预测的可靠性 .结果显示其中 4个 AS- ODNsIC50 值明显低于阳性对照 ISIS352 1 (P<0 .0 5) . 8个AS- ODNs与 ISIS352 1的实测 IC50 与 QSAR方程预测相符 ,实测与预测 IC50 之间相关系数为 0 .76(P<0 .0 5) .两个 AS- ODNs,AP1 2 61 (2 0 )和 AP0 1 86(2 0 )的实测 IC50 与预测不符 .结果提示 QSAR方程一定程度上反映了 AS- ODNs活性与靶结构的关系 ,对预测反义药物生物活性有益 .但 QSAR方程难以解释的其他因素需进一步研究以优化反义药物设计
In the past, QSAR analysis was performed on the quantitative structure-activity relationship (QSAR) analysis of 34 antisense drugs (AS-ODNs) designed for the secondary structure of protein kinase C-α m RNA.In this study, 10 AS- ODNs validated the reliability of the QSAR equation for the prediction of drug activity.The results showed that the IC50 values of four AS-ODNs were significantly lower than the positive control ISIS352 1 (P <0.05) .The IC50 and QSAR of 8 AS-ODNs and ISIS352 1 The correlation between the measured and predicted IC50 was 0.76 (P <0.05). The measured IC50 values of two AS-ODNs, AP1 2 61 (2 0) and AP0 1 86 (2 0) The results suggest that the QSAR equation reflects to some extent the relationship between the activity of AS-ODNs and the target structure, which is beneficial to predict the biological activity of antisense drugs.However, other factors that are difficult to explain by the QSAR equation need to be further studied to optimize antisense drug design