中文摘要：

目的在抑制性CpG寡核苷酸（CpG-N ODN）分子设计的基础上，选择部分序列加以合成并对其生物学活性进行鉴定，筛选出能够拮抗细菌DNA的CpG-N ODN。方法对合成的10条CpG ODN进行生物学活性的初筛和复筛，观察其自身的刺激性及其对CpG-SODN诱导的TNF-α释放的抑制作用。使用RNAstructure version3．71预测CpG ODN的二级结构及自由能，根据10条CpG ODN构效关系分析结果，对CpG-N ODN分子进行再设计，并从中选择11个序列进行生物活性的筛选。结果首次合成的10条CpG ODN仅1条是对细菌DNA拮抗作用较弱的CpG-N ODN。通过对其构效关系进行分析，推测CpG ODN的生物活性可能与自由能相关。在此基础上对CpG-N ODN分子进行了再设计，合成的11条CpG ODN中有5条是拮抗作用较强的CpG-N ODN。结论获得了6条CpG-N ODN。CpG ODN的生物活性可能与自由能密切相关。

英文摘要：

Objective To obtain a potent bacterial DNA antagonizing CpG oligonucleotides （CpG-N ODN） from the structures of Adv2, 5 DNA. Methods Ten putative CpG-N ODNs were synthesized and investigated. Their abilities to inhibit the TNF-α release from hPBMC were observed. Based on the above results, the putative CpG-N ODN was redesigned according to the relationship between the structure and free energy using RNA structure software （version 3. 71）. Eleven putative CpG-N ODNs were synthesized and screened. Results Out of the ten initial CpG ODNs, ODN101 was the only CpG-N ODN with weak activity to inhibit TNF-α release from hPBMC induced by CpG-N ODN. After redesign, five CpG-N ODNs with strong activity were confirmed Conclusion Six CpG-N ODNs were obtained with activity to inhibit TNF-α release from hPBMC induced by CpG-N ODN.