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目的 通过计算机模拟bcl 2基因的mRNA二级结构 ,优化反义药物设计。方法 用计算机程序Mfold软件模拟mRNA的二级结构后 ,筛选出不稳定的二级结构区域 ,进行反义药物设计 ;用实验评价所设计反义药物的生物效应 ,筛选出的bcl 2反义寡核苷酸对白血病细胞株HL 60、K5 62生物学活性的影响。结果 有 2个位点的反义寡核苷酸在计量为 10 μmol·L-1以上时 ,能明显抑制细胞的生长活性。结论 bcl 2mRNA二级结构的模拟是设计反义药物的一条新的途径
Objective To optimize antisense drug design by computer mimicking the mRNA secondary structure of bcl 2 gene. Methods After the secondary structure of mRNA was simulated by computer program Mfold software, the unstable secondary structure regions were screened for antisense drug design; the biological effects of designed antisense drugs were evaluated experimentally and the bcl 2 antisense oligonucleotides were screened out. Effects of Nucleotides on the Biological Activity of Leukemia Cell Lines HL 60, K5 62. Results The antisense oligodeoxynucleotides with two sites could significantly inhibit the cell growth activity when measured at 10 μmol·L-1 or more. Conclusion The simulation of bcl 2 mRNA secondary structure is a new way to design antisense drugs