Stabilization of the i-motif structure by the intra-strand cross-link formation.

Stabilization of the i-motif structure by the intra-strand cross-link formation.
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DOI:
10.1016/j.bmcl.2015.05.064
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发表时间:
2015-08
影响因子:
2.7
通讯作者:
Kenji Kikuta;Haishun Piao;J. Brazier;Y. Taniguchi;Kazumitsu Onizuka;F. Nagatsugi;S. Sasaki
Kenji Kikuta;Haishun Piao;J. Brazier;Y. Taniguchi;Kazumitsu Onizuka;F. Nagatsugi;S. Sasaki
中科院分区:
医学4区
文献类型:
--
作者:
Kenji Kikuta;Haishun Piao;J. Brazier;Y. Taniguchi;Kazumitsu Onizuka;F. Nagatsugi;S. Sasaki

文献摘要

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它们的基序结构是由含有胞嘧啶片段的寡核苷酸在酸性条件下形成的。在生理条件下,由于其生物学作用,其i基序的折叠引起了极大的兴趣。在这项研究中,我们研究了链内交联对i基序结构稳定性的影响。将4-乙烯基取代的胸苷类似物(T-vinyl)掺入人端粒互补链的5′端,与内部腺嘌呤形成链内交联。在酸性条件下,链内交联的二基序显示出与天然二基序相似的CD谱,随着pH的升高,二基序转变为无规卷曲,从二基序转变为无规卷曲的pH中点从天然二基序的pH6.1升高到交联二基序的pH6.8。通过CD和UV测量热熔融行为获得了热力学参数,并确定由于有利的熵效应,链内交联的双基序是稳定的。因此,该研究清楚地表明了链内交联对于稳定其基序结构的有效性。
Thei-motif structures are formed by oligonucleotides containing cytosine tracts under acidic conditions. The folding of thei-motif under physiological conditions is of great interest because of its biological role. In this study, we investigated the effect of the intra-strand cross-link on the stability of thei-motif structure. The 4-vinyl-substituted analog of thymidine (T-vinyl) was incorporated into the 5′-end of the human telomere complementary strand, which formed the intra-strand cross-link with the internal adenine. The intra-strand cross-linkedi-motif displayed CD spectra similar to that of the naturali-motif at acidic pH, which was transformed into a random coil with the increasing pH. The pH midpoint for the transition from thei-motif to random coil increased from pH 6.1 for the natural one to pH 6.8 for the cross-linked one. The thermodynamic parameters were obtained by measuring the thermal melting behaviors by CD and UV, and it was determined that the intra-strand cross-linkedi-motif is stabilized due to a favorable entropy effect. Thus, this study has clearly indicated the validity of the intra-strand cross-linking for stabilization of thei-motif structure.