Synthesis and hybridization properties of modified oligodeoxynucleotides carrying non-natural bases.

Synthesis and hybridization properties of modified oligodeoxynucleotides carrying non-natural bases.
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携带非天然碱基的修饰寡脱氧核苷酸的合成和杂交特性。

DOI:
10.1002/cbdv.200800239
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发表时间:
2009
影响因子:
2.9
通讯作者:
Eritja,Ramon
Eritja,Ramon
中科院分区:
化学3区
文献类型:
--
作者:
Avino,Anna;Perez-Rentero,Sonia;Garibotti,AlejandraV;Siddiqui,MaqboolA;Marquez,VictorE;Eritja,Ramon

文献摘要

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已经研究了非天然碱基的存在对寡脱氧核苷酸特性的影响。首先,制备携带2'-deoxyzebularine的寡脱氧核苷酸,并通过DNA熔解实验确定携带该类似物的双链体的稳定性。熔解温度和热力学数据表明2'-脱氧zebularine优先于2'-脱氧鸟苷,2'-脱氧鸟苷的行为类似于2'-脱氧胞苷类似物,由于4位上缺乏氨基,形成不太稳定的碱基对。此外,研究了携带多个天然和非天然碱基(包括作为中心错配的2'-deoxyzebularine)的自互补寡脱氧核苷酸的双链体-发夹平衡。根据序列中间存在的碱基,可能会影响调节双链体-发夹平衡的双分子双链体的稳定性。镁离子被证明可以优先稳定双分子双链体形式。结果表明了修饰的重要性以及阳离子在改变结构平衡中的作用。
The impact of the presence of nonnatural bases on the properties of oligodeoxynucleotides has been studied. First, oligodeoxynucleotides carrying 2′‐deoxyzebularine were prepared, and the stability of duplexes carrying this analogue was determined by DNA melting experiments. Melting temperatures and thermodynamic data indicated the preference of 2′‐deoxyzebularine for 2′‐deoxyguanosine, which behaves as a 2′‐deoxycytidine analogue, forming a less stable base pair due to the absence of the amino group at position 4. Moreover, the duplex–hairpin equilibrium of a self‐complementary oligodeoxynucleotide carrying several natural and nonnatural bases including 2′‐deoxyzebularine as a central mispair, was studied. Depending on the base present in the middle of the sequence, it is possible to affect the stability of the bimolecular duplex modulating the duplex–hairpin equilibrium. Magnesium ions were shown to stabilize preferentially the bimolecular duplex form. The results indicate the importance of the modifications and the role of cations in shifting the structural equilibrium.