Formation of Stable DNA Loops by Incorporation of Nonpolar, Non-Hydrogen-Bonding Nucleoside Isosteres.
Formation of Stable DNA Loops by Incorporation of Nonpolar, Non-Hydrogen-Bonding Nucleoside Isosteres.
复制标题
通过掺入非极性、非氢键核苷等排体形成稳定的 DNA 环。
DOI：
10.1002/anie.199607431
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Kool,EricT
中科院分区：
文献类型：
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作者：
Ren,Xiao-Feng;Schweitzer,BarbaraA;Sheils,CharlesJ;Kool,EricT
发夹环是自然界中折叠的RNA和DNA序列中普遍存在的结构。最近的报告指出了某些环序列的特殊稳定性。例如，具有序列GNRA和UUCG的RNA四核苷酸环（四环）比其他四环更稳定，并且在自然界中高度保守。[1，2]在某些情况下，具有序列GAAA的DNA四环在双链体DNA中异常稳定;[3]在三链体结构中，环序列CTTTG据报道也特别稳定。[4]在大多数或所有这些情况下，结构研究已经暗示或确定碱基和/或磷酸盐之间的环内氢键作为重要的结构特征。这一点早已得到承认。然而，水溶液中氢键较弱。在这方面，对RNA中GAAA四环中氢键的详细研究得出结论，单个氢键对整体稳定性的贡献相对较小。[5]虽然不太清楚，但也已知碱基堆积对核酸稳定性的贡献至少与氢键一样重要。[6-8]在RNA和DNA的环结构的研究还没有普遍解决的相对重要性，碱基堆积和氢键在稳定这样的loop.We进行了一个程序，设计和合成非氢键核苷类似物，用作探针的生物非共价相互作用的寡核苷酸和核酸一般。[9]我们现在描述三个这样的电子等排体掺入DNA环，我们已经发现，这样的取代可以导致显着稳定的双螺旋和三螺旋折叠结构的DNA。
Hairpin loops are ubiquitous structures found in folded RNA and DNA sequences in nature. Recent reports have noted special stability for certain loop sequences. For example, RNA tetranucleotide loops (tetraloops) having the sequence GNRA and UUCG are more stable than other tetraloops and are highly conserved in nature.[1, 2] DNA tetraloops having the sequence GAAA, in certain contexts, are unusually stable in duplex DNA;[3] in triplex structures the loop sequence CTTTG has been reported to be especially stable as well.[4] In most or all of these cases, structural study has either implicated or identified intraloop hydrogen bonds between bases and/or phosphates as important structural features. It has long been recognized. however, that hydrogen bonds in aqueous solution are weak. In this regard a detailed study of hydrogen bonding in the GAAA tetraloop in RNA concluded that single hydrogen bonds contribute relatively little to the overall stability.[5] While less well understood, base stacking is also known to be at least as important a contribution to nucleic acid stability as hydrogen bonding.[6–8] Studies of loop structures in RNA and DNA have not generally addressed the relative importance of base stacking and hydrogen bonding in stabilizing such loops.We have undertaken a program to design and synthesize non-hydrogen-bonding nucleoside analogues to be used as probes of the biological noncovalent interactions of oligonucleotides and nucleic acids in general.[9] We now describe the incorporation of three such isosteres into DNA loops, and we have found that such substitutions can lead to significant stabilization of double-and triple-helical folded structures in DNA.