5-炔基-2′-脱氧尿苷的合成及其对掺入到寡核苷酸中的影响  

Syntheses of 5-alkynyl-2′-deoxyuridines and their incorporation into oligonucleotides

作　　者：余建鑫[1] 张万年[1] 张蕾[1] 周有骏[1] 吕加国[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》2002年第5期254-257,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的为寻找具有较好反义活性的药物 ,设计并合成了一类 2′ 脱氧尿苷 5 位修饰的寡核苷酸。方法以 5′ O (4,4′ 二甲氧三苯甲基 )脱氧碘苷为起始原料 (Ⅰ ) ,用双 (三苯基膦 )氯化钯和碘化亚铜偶合末端炔烃 ,得到一系列相应的 5 炔基脱氧尿苷 (Ⅱ )。化合物Ⅱ的 3′ 位经 (2 氰乙基N ,N 二异丙基 )氯化亚磷酰胺缩合后 ,应用标准固相DNA合成法掺入到寡核苷酸中。结果共合成了 4条 2′ 脱氧尿苷 5 位带炔基修饰的寡核苷酸 ,考察了它们的杂交性质 ,测定了与互补DNA的解链温度Tm 值。结论此类修饰的寡核苷酸与对照的天然寡核苷酸杂交亲和力有一定的提高 ,其中丙炔基修饰的寡核苷酸解链温度Tm 值上升约 2 2℃。Aim To screen more efficient antisense drugs,a series of new oligonucleotides(ODNs)modified at the 5 position of 2′ deoxyuridine was designed and synthesized.Methods Coupling of terminal alkynes with 5 iodo 5′ O (4,4′ dimethoxytrityl) 2′ deoxyuridine(Ⅰ) in the presence of dichlorobis(triphenylphosphine)palladium and copper iodine gave the corresponding 5 alkynyl 2′ deoxyuridines(Ⅱ).These compounds(Ⅱ),of which 3′ hydroxyl groups were protected by(2 cyanoethyl N,N diisopropyl)chlorophosphoramidite,were incorporated into oligonucleotides by using the standard solid phase synthesis of the DNA chemistry on the controlled pore glass(CPG)support by the phosphoramidite method.Results The 4 new oligonucleotides(ODN Ⅱ ODN Ⅴ)containing 5 modified 2′ deoxyuridines have been synthesized.Also,the melting temperatures( T m)of these ODNs with their DNA complements were determined.Conclusion The oligonucleotides containing the 5 alkynyl 2′ deoxyuridines showed an increase in melting temperatures relative to the native duplex.Of those modified residues which have been incorporated into oligonucleotides,the 5 propynyl 2′ deoxyuridine was found to impart the greatest change in stability upon the duplex with an increase of 2 2℃ per base modification.

关 键 词：5-炔基-2'-脱氧尿苷 合成 寡核苷酸 温度 

分 类 号：R914[医药卫生—药物化学]