Porphyrin binding to quadruplexed T4G4

Porphyrin binding to quadruplexed T4G4
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DOI:
10.1021/bi973009v
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发表时间:
1998-03-03
期刊:
影响因子:
2.9
通讯作者:
Sheardy, RD
Sheardy, RD
中科院分区:
生物学3区
文献类型:
--
作者:
Anantha, NV;Azam, M;Sheardy, RD

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我们最近报道了阳离子诱导的一般序列C(4)T(4)G(4)T(1-4)G(4)的DNA寡聚体自组装成高分子量多链结构[Marotta,S. P.,坦布里,宾夕法尼亚州,和Sheardy,R. D.(1996)Biochemistry 35,10484-10492]。拟议结构的体系结构由一系列四个叶状G(4)四分体组成,通过一条或两条T1-4链拴在一起,因此类似于一个带有周期性“口袋”的长四面空心管。这些口袋具有静电,氢键和疏水接触点,应该是小分子结合的理想候选者。为了评估使用卟啉作为这些结构的探针的潜力,我们研究了四(4-N-甲基吡啶基)卟啉(H2 TMPyP)与由T(4)G(4)形成的简单四链体和由CGCGATATCGCG形成的双链体的相互作用。可见光吸收、圆二色性和荧光能量转移研究表明,H2 TMPyP在低[卟啉]/[DNA分子]比率下通过嵌入结合到双链体和四链体两者,即,在存在过量潜在DNA结合位点的情况下。Scatchard图的分析表明,H(2)TMPyP以高亲和力结合两种DNA二级结构,但结合四链体的亲和力是双链体的2倍。
We have recently reported the cation-induced self-assembly of DNA oligomers of the general sequence C(4)T(4)G(4)T(1-4)G(4) into high-molecular weight multistranded structures [Marotta, S. P., Tamburri, P. A., and Sheardy, R. D. (1996) Biochemistry 35, 10484-10492]. The architecture of the proposed structure consists of a series of four leafed G(4) tetrads tethered together via one or two T1-4 strands and thus resembles a long four-sided hollow tube with periodic "pockets". These pockets possess electrostatic, hydrogen bonding, and hydrophobic contact points and should be ideal candidates for the binding of small molecules. To assess the potential of using porphyrins as probes for these structures, we have investigated the interaction of tetrakis (4-N-methylpyridyl) porphine (H2TMPyP) with the simple quadruplex formed by T(4)G(4) and with the duplex formed by CGCGATATCGCG. Visible absorption, circular dichroism, and fluorescent energy transfer studies indicate that H2TMPyP binds to both the duplex and quadruplex via intercalation at low [porphyrin]/[DNA molecule] ratios, i.e., in the presence of excess potential DNA binding sites. Analyses of Scatchard plots show that H(2)TMpyP binds with high affinity to both DNA secondary structures but binds to the quadruplex with an affinity 2 times greater than that of the duplex.