Nucleosides and oligonucleotides containing 1,2,3-triazole residues with nucleobase tethers: Synthesis via the azide-alkyne 'click' reaction
Nucleosides and oligonucleotides containing 1,2,3-triazole residues with nucleobase tethers: Synthesis via the azide-alkyne 'click' reaction
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DOI：
10.1016/j.bmc.2008.08.026
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发表时间：
2008-09-15
影响因子：
3.5
通讯作者：
Seela, Frank
中科院分区：
文献类型：
--
作者：
Chittepu, Padmaja;Sirivolu, Venkata Ramana;Seela, Frank
通过铜（I）催化的N-9炔丙基嘌呤或N-1炔丙基嘧啶与甲苯酰基保护的1-叠氮基-2-脱氧呋喃核糖2的1，3-偶极环加成反应，然后用NaOMe/ MeOH或aq NH3处理，制备了一系列与DNA核碱基连接的新型1，2，3-三唑核苷。报道了此类化合物对选定的RNA病毒的抗病毒活性。以炔丙基化尿嘧啶1a和炔丙基化腺嘌呤1c与叠氮香豆素15为原料合成了具有强荧光的1，2，3-三唑类化合物16和17，并对其荧光性质进行了研究。使用亚磷酰胺结构单元将核苷4和6掺入DNA中，并用于固相合成。解链实验表明，当这些1，2，3-三唑核苷与规范碱基以及脱碱基位点相对放置时，它们对双链体稳定性具有负面影响。由于三唑环引起的结构变化，连接到三唑环上的核碱基不能参与与相对碱基的碱基对形成。当位于寡核苷酸末端时，这种核苷的堆叠保持了DNA双链体的稳定性。的双链结构进行了研究，分子建模支持熔化实验的结果。(C)2008爱思唯尔有限公司保留所有权利。
A series of novel 1,2,3-triazole nucleosides linked to DNA nucleobases were prepared via copper(I)catalyzed 1,3-dipolar cycloaddition of N-9 propargylpurines or N-1 propargylpyrimidines with the tolouyl protected 1-azido-2-deoxyribofuranose 2 followed by treatment with NaOMe/ MeOH or aq NH3. The antiviral activity of such compounds against selected RNA viruses is reported. The strongly fluorescent 1,2,3-triazole compounds 16 and 17 were synthesized from propargylated uracil 1a and propargylated adenine 1c with coumarin azide 15, and the fluorescence properties were studied. The nucleosides 4 and 6 were incorporated into DNA using the phosphoramidite building blocks and employed in solid-phase synthesis. Melting experiments demonstrated that such 1,2,3-triazole nucleosides have a negative impact on the duplex stability when they are placed opposite to the canonical bases as well as abasic sites. The nucleobases attached to the triazole ring cannot involve in the base pair formation with the opposite bases because of the structural variations induced by the triazole ring. The stacking of such nucleosides when positioned at the end of oligonucleotides retains the stability of DNA duplexes. The duplex structures were studied by molecular modelling which support the results of melting experiments. (C) 2008 Elsevier Ltd. All rights reserved.