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首页> 外文期刊>Biochemical Pharmacology >Structural optimization and anti-allergic activity of nucleotide aptamers target to C epsilon 3-C epsilon 4
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Structural optimization and anti-allergic activity of nucleotide aptamers target to C epsilon 3-C epsilon 4

机译：核苷酸适体靶向Cε3-C epsilon 4的结构优化和抗过敏活性

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Nucleic acid aptamers have shown a broad application prospect in basic research, clinical diagnosis and treatment, new drug development and various other fields. We have screened the DNA aptamer A1 and A2 target at C epsilon 3-C epsilon 4 with high affinity and specificity, another aptamer A8, no affinity with C epsilon 3-C epsilon 4 protein, was as a negative control in this study. The structures of aptamer A1 and A2 were optimized using the deletion method, complementary sequence method, and point mutation method, to make them perform biological functions better, improve the pertinence of the subsequent modification and study the mechanism of action of aptamers coupled C epsilon 3-C epsilon 4. Additionally, the affinity was detected using competitive ELISA, then the most optimal and minimalist aptamer G39-A1-29C was obtained. The results indicated that the G39-A1-29C can significantly inhibit the IgE-dependent cell degranulation, but no effect in IgE-independent manner, and have a notable therapeutic effect with dose-dependent on PCA experiments in vivo. Moreover, it is found that the aptamer maintains the secondary structure through the fixed sequence, consecutive four GC pairings can significantly increase the binding affinity, and the G base on the loop region of A1 may be the key sites for binding to the domain of the target protein C epsilon 3-C epsilon 4. Therefore, the stem-loop structure of A1 is the structural basis of its binding, too short sequence cannot maintain the secondary structure, so that its affinity is significantly reduced. The results facilitated the modification and chemical synthesis of aptamers in next work, which provided the foundation for the development of new drugs for the treatment of allergy diseases.
机译：核酸适体已经显示了基础研究的广泛应用前景，临床诊断和治疗，新药开发和各种其他领域。我们在C epsilon 3-C epsilon4中筛选了DNA适体A1和A2靶，具有高亲和力和特异性，另一个适体A8，与Cε3-Cε4蛋白没有亲和力，是本研究中的阴性对照。使用缺失方法，互补序列方法和点突变方法优化适体A1和A2的结构，使它们更好地进行生物学功能，改善随后的修饰和研究适体耦合C epsilon 3的作用机制-Cε4.此外，使用竞争力的ELISA检测亲和力，然后获得最佳和极简主义适体G39-A1-29c。结果表明，G39-A1-29C可以显着抑制IgE依赖性细胞脱粒，但无依赖于IgE的方式没有影响，并且具有显着的治疗效果，其剂量依赖于体内PCA实验。结果发现，适体通过固定序列保持二次结构，连续四个GC配对可以显着增加结合亲和力，并且A1的环路区域的G基部可以是用于绑定到域的关键位置靶蛋白Cε3-Cε4.因此，A1的茎环结构是其结合的结构基础，过短序列不能保持二次结构，从而显着降低其亲和力。结果促进了下一个工作中适体的改性和化学合成，为开发新药进行了治疗过敏疾病的基础。

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