N^4-烷基-5-甲基-2′-脱氧胞苷的合成及其掺入到寡核苷酸中对杂交亲和力的影响  

Synthesis of N4-alkyl-5-methyl-2′-deoxycytidines andtheir incorporation into oligonucleotides

作　　者：余建鑫[1] 张万年[1] 李科[1] 姚建忠[1] 章玲[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2007年第4期199-203,共5页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20302013)

摘　　要：目的为寻找具有较好反义活性的药物,设计并合成脱氧胞苷5-甲基-N4-烷基修饰的寡核苷酸。方法以胸苷为起始原料,合成了一系列N4-烷基取代的5-甲基-5′-O-(4,4′-二甲氧三苯甲基)-2′-脱氧胞苷-3′-O-(2-氰乙基-N,N-二异丙基)氨基亚磷酸酯,并把它们掺入到寡核苷酸中。结果与结论共合成了4条5-甲基-N4-烷基修饰的寡核苷酸,考察了它们的杂交性质,测定了它们与互补DNA的解链温度Tm值。脱氧胞苷的5-位甲基取代物能够增加寡核苷酸双链的稳定性,而N4-位的修饰则使双链稳定性下降。Aim To design and synthesize a series of new oligodeoxynucleotides（ODNs） modified at deoxycy- tidine by 5-methyl-N^4-alkyl ring and to screen more efficient antisense drugs. Methods A series of N^4-alkyl modified 5-methyl-5＇-O-（4, 4＇-dimethoxytrityl）-2＇-deoxycytidine-3＇-O-（2-cyanoethyl N, N-diisopropyl） phosphoramidite compounds was synthesized and incorporated into oligonucleotides. Results and conclusion Four new oligonucleotides containing 5-methyl-Ng-alkyl-deoxycytidines were synthesized. Also, the melting temperatures（Tin） of these ODNs with their DNA complements were determined. The hybridizing affinity of the ODNs with their DNA complements disclosed a different effect of 5-methyl-N^4-alkyl of deoxycytidines on the double helix stability. 5-Methyl substitution increased the stability of the ODN duplexes while N^4-alkylation caused a profound destabilization of the double helix.

关 键 词：脱氧胞苷 反义寡核苷酸 胸苷 解链温度 杂交 

分 类 号：R914[医药卫生—药物化学]