NMR studies of DNA single strands and DNA:RNA hybrids with and without 1-propynylation at C5 of oligopyrimidines.
NMR studies of DNA single strands and DNA:RNA hybrids with and without 1-propynylation at C5 of oligopyrimidines.
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DNA 单链和 DNA:RNA 杂交体的 NMR 研究，在寡嘧啶的 C5 处有或没有 1-丙炔化。
DOI：
10.1021/ja021285d
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Turner,DouglasH
中科院分区：
文献类型：
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作者：
Znosko,BrentM;Barnes3rd,ThomasW;Krugh,ThomasR;Turner,DouglasH
DNA中连续的嘧啶在C5位的1-丙炔化可以提高DNA：RNA杂交在37℃下的稳定性，取代度超过1千卡/摩尔[Barnes，T.W.，III；Turner，D.H.J.Am化学。编号2001,123,4107−4118]。为了提供丙炔化反应的结构后果的信息，用二维核磁共振波谱研究了几种寡核苷酸的结构。在30℃和200ms的混合时间下，在H6−H1‘区观察到5’(DCPCPUPCPCPUPUP)(SsPrODN)的残基内核Overhauser效应谱交叉峰，但没有观察到5‘(DCCUCCUU)(SsODN)的交叉峰，这表明丙炔化单链是预组织的。5‘(DCPCPUPCPCPUPUP)3’：3‘(RGAGGAGGAAAU)5’(PrODN：RNA)，5‘(DCCPUPCPCPUPUP)3’：3‘(RGAGGAGGAAAU)5’(sPrODN1：RNA)和5‘(DCCUCCUU)3’：3‘(RGAGGAGGAAAU)5’(ODN：RNA)的核磁共振结构表明它们的全局结构几乎相同。然而，核磁共振数据表明，sPrODN1：RNA的5‘端比PrODN：RNA的5’端更具活力。在丙炔化的双链中，丙炔基团堆积在5‘-碱基的芳环上并延伸到主槽中。结果表明，丙炔化双链的稳定性增加是由于丙炔化单链的预组织和双链中不同的相互作用所致。丙炔基提供体积排斥、增强堆积和可能的不同溶剂化。
The 1-propynylation at C5 of consecutive pyrimidines in DNA can enhance DNA:RNA hybrid stability at 37 °C by over 1 kcal/mol of substitution [Barnes, T. W., III; Turner, D. H.J. Am. Chem. Soc.2001,123, 4107−4118]. To provide information on the structural consequences of propynylation, two-dimensional NMR spectroscopy was used to study the structures of several oligonucleotides. Intraresidue nuclear Overhauser effect spectroscopy cross peaks were observed at 30 °C and a 200 ms mixing time in the H6−H1‘ region for 5‘(dCPCPUPCPCPUPUP) (ssPrODN) but not for 5‘(dCCUCCUU) (ssODN), suggesting preorganization of the propynylated single strand. NMR structures of the duplexes 5‘(dCPCPUPCPCPUPUP)3‘:3‘(rGAGGAGGAAAU)5‘ (PrODN:RNA), 5‘(dCCPUPCPCPUPUP)3‘:3‘(rGAGGAGGAAAU)5‘ (sPrODN1:RNA), and 5‘(dCCUCCUU)3‘:3‘(rGAGGAGGAAAU)5‘ (ODN:RNA) indicate that their global structures are almost identical. The NMR data, however, suggest that the 5‘-end of sPrODN1:RNA is more dynamic than that of PrODN:RNA. In the propynylated duplexes, the propyne group stacks on the aromatic ring of the 5‘-base and extends into the major groove. The results suggest that the increased stability of the propynylated duplexes is caused by preorganization of the propynylated single strand and different interactions in the double strand. The propynyl group provides volume exclusion, enhanced stacking, and possibly different solvation.