Interactions Between Spermine-Derivatized Tentacle Porphyrins and The Human Telomeric DNA G-Quadruplex.
Interactions Between Spermine-Derivatized Tentacle Porphyrins and The Human Telomeric DNA G-Quadruplex.
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DOI：
10.3390/ijms19113686
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发表时间：
2018-11-21
影响因子：
5.6
通讯作者：
Yatsunyk LA
中科院分区：
文献类型：
--
作者：
Sabharwal NC;Chen J;Lee JHJ;Gangemi CMA;D'Urso A;Yatsunyk LA
富含G的DNA序列有可能折叠成非规范的G-四链(GQ)结构，与衰老和人类疾病，特别是癌症有关。因为稳定端粒和癌基因启动子上的GQs可以预防癌症，所以人们有兴趣开发选择性靶向GQs的小分子。本文通过紫外可见光谱、圆二色谱(CD)、荧光光谱、共振光散射和荧光共振能量转移(FRET)等方法研究了meso-tetrakis-(4-carboxysperminephenyl)porphyrin(TCPPSpm4)及其锌(II)衍生物与人端粒DNA(TEL22)的相互作用。UV-Vis滴定表明，TCPPSpm4和ZTCPPSpm4的结合常数分别为4.7×10 6和1.4×10 7M−1，结合化学计量比分别为2-4：1和10-12：1。作业图数据、CD滴定和RLS数据支持高化学计量比。FRET熔融表明，TCPPSpm4在7.5 eq时使Tel22稳定36±2℃，在~20 eq时至少使Tel22稳定33±2℃。与其高结合化学计量比相一致，需要ZnTCPPSpm4的存在才能实现Tel22的显著稳定。FRET竞争研究表明，这两种卟啉对人类端粒GQ和双链DNA都有轻微的选择性。结合光谱研究，指出末端堆积和卟啉自结合是主要的结合模式。这项工作加深了我们对配体与Gq DNA相互作用的理解。
G-rich DNA sequences have the potential to fold into non-canonical G-Quadruplex (GQ) structures implicated in aging and human diseases, notably cancers. Because stabilization of GQs at telomeres and oncogene promoters may prevent cancer, there is an interest in developing small molecules that selectively target GQs. Herein, we investigate the interactions of meso-tetrakis-(4-carboxysperminephenyl)porphyrin (TCPPSpm4) and its Zn(II) derivative (ZnTCPPSpm4) with human telomeric DNA (Tel22) via UV-Vis, circular dichroism (CD), and fluorescence spectroscopies, resonance light scattering (RLS), and fluorescence resonance energy transfer (FRET) assays. UV-Vis titrations reveal binding constants of 4.7 × 106 and 1.4 × 107 M−1 and binding stoichiometry of 2–4:1 and 10–12:1 for TCPPSpm4 and ZnTCPPSpm4, respectively. High stoichiometry is supported by the Job plot data, CD titrations, and RLS data. FRET melting indicates that TCPPSpm4 stabilizes Tel22 by 36 ± 2 °C at 7.5 eq., and that ZnTCPPSpm4 stabilizes Tel22 by 33 ± 2 °C at ~20 eq.; at least 8 eq. of ZnTCPPSpm4 are required to achieve significant stabilization of Tel22, in agreement with its high binding stoichiometry. FRET competition studies show that both porphyrins are mildly selective for human telomeric GQ vs duplex DNA. Spectroscopic studies, combined, point to end-stacking and porphyrin self-association as major binding modes. This work advances our understanding of ligand interactions with GQ DNA.
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影响因子：
2.9
作者：
Anantha, NV;Azam, M;Sheardy, RD
通讯作者：
Sheardy, RD
DOI：
10.1007/978-94-007-2172-2_4
发表时间：
2012-01-01
期刊：
INTERPLAY BETWEEN METAL IONS AND NUCLEIC ACIDS
影响因子：
--
作者：
Campbell, Nancy H.;Neidle, Stephen
通讯作者：
Neidle, Stephen
影响因子：
15
作者：
Han, FXG;Wheelhouse, RT;Hurley, LH
通讯作者：
Hurley, LH
影响因子：
1.5
作者：
Gangemi, Chiara M. A.;D'Agostino, Bruno;D'Urso, Alessandro
通讯作者：
D'Urso, Alessandro
影响因子：
14.9
作者：
Ambrus A;Chen D;Dai J;Bialis T;Jones RA;Yang D
通讯作者：
Yang D