拮抗细菌DNA的CpG-N ODN筛选  

Screening of bacterial DNA antagonizing CpG oligodeoxynucleotides

作　　者：王良喜[1,2] 鲁永玲[1] 丁国富[1] 罗平[1] 周红[1] 

机构地区：[1]第三军医大学基础部药理学教研室,重庆400038 [2]解放军第97医院烧伤科

出　　处：《解放军医学杂志》2007年第1期53-56,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金资助项目(30271512)

摘　　要：目的在抑制性CpG寡核苷酸(CpG-NODN)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-NODN。方法对合成的10条CpGODN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RNAstructureversion3.71预测CpGODN的二级结构及自由能,根据10条CpGODN构效关系分析结果,对CpG-NODN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CpGODN仅1条是对细菌DNA拮抗作用较弱的CpG-NODN。通过对其构效关系进行分析,推测CpGODN的生物活性可能与自由能相关。在此基础上对CpG-NODN分子进行了再设计,合成的11条CpGODN中有5条是拮抗作用较强的CpG-NODN。结论获得了6条CpG-NODN。CpGODN的生物活性可能与自由能密切相关。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.

关 键 词：DNA 细菌 脓毒症 CPG基序 抑制性CpG寡核苷酸 分子设计 

分 类 号：R916[医药卫生—药学] R342