二级结构模拟辅助MTB脱氧核酶潜在作用靶点预测

Prediction of Deoxyribozyme's Potential Target Assistant by Sketch of Secondary Structure

异柠檬酸裂解酶(ICL)是结核病病原体结核分枝杆菌(MTB)乙醛酸循环中的关键酶,可作为抗结核新型药物治疗的潜在靶点。脱氧核酶(DRz)是一类独特的、具备酶活性的单链小分子DNA。实验针对MTBICL基因mRNA片段,通过二级结构模拟预测理论上适合与不适合DRz10～23作用的位点,据此设计针对ICL基因mRNA片段两种不同位点的DRz,并在体外水平上观察两种DRz对MTBICL基因mRNA片段的切割作用,以此验证底物二级结构模拟辅助MTB脱氧核酶潜在作用靶点预测的可行性。结果显示,底物二级结构模拟能够辅助预测MTB脱氧核酶潜在作用靶点,为探讨其作为抗结核病基因药物的可能提供实验基础。

Isocitrate lyase （ICL） which plays a pivotal role in the glyoxylate cycle of mycobacterium tuberculosis （MTB） could be a potential target against mycobacterium tuberculosis. Deoxyribozyme （DRz） is a small single-strand, enzymatic DNA molecule. Assistant by sketch of secondary structure, appropriate and not appropriate target sequences of MTB ICL mRNA were predicted. Two DRzs were designed targeting above sequences respectively. To affirm feasibility of this kind of prediction, in vitro cleavage of MTB ICL mRNA segment by DRz-ICLcf and DRz-ICI-cj were performed. The results showed that sketch of secondary structure could indeed predict potential target of DRz. This research will provide basis for developing DRz as a novel antimicrobial agent against MTB.