Formation of a complex of 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin with G-quadruplex DNA
Formation of a complex of 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin with G-quadruplex DNA
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DOI：
10.1021/bi052442z
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发表时间：
2006-06-06
期刊：
影响因子：
2.9
通讯作者：
Yamamoto, Yasuhiko
中科院分区：
文献类型：
--
作者：
Mita, Hajime;Ohyama, Takako;Yamamoto, Yasuhiko
水溶性阳离子卟啉5，10，15，20-tetrakis(N-methylpyridinium-4-yl)-21H，23H-porphyrin(TmPyP4)因其独特的与核酸相互作用的物理化学性质及其治疗应用而受到广泛研究。为了阐明TmPyP4与DNA之间的分子识别模式，研究了TmPyP4与人端粒单个重复序列d(TTAGGG)形成的平行G-四链DNA之间的复合物。研究表明，TmPyP4插入到[d(TTAGGG)](4)的A3pG4步骤中，结合常数为6.2×10(6)M-1，化学计量比为1：1。TmPyP4与[d(TTAGGG)]4的A3pG4步骤的结合是通过TmPyP4的卟啉环与G4四联体以及G-四链DNA的A3碱基的pi-pi堆积作用而稳定的。这些发现为以高亲和力和特异性与DNA结合的卟啉衍生物的设计提供了新的见解。
A water-soluble cationic porphyrin, 5,10,15,20-tetrakis(N-methylpyridinium-4-yl)-21H,23H-porphyrin (TmPyP4), has been studied extensively because of its unique physicochemical properties that lead to interactions with nucleic acids, as well as its therapeutic application. Formation of a complex between TmPyP4 and parallel G-quadruplex DNA formed from a single repeat sequence of the human telomere, d(TTAGGG), has been characterized in an effort to elucidate the mode of molecular recognition between TmPyP4 and the DNA. The study demonstrated that TmPyP4 intercalates into the A3pG4 step of [d( TTAGGG)](4) with an association constant of 6.2 x 10(6) M-1 and a stoichiometric ratio of 1:1. The binding of TmPyP4 to the A3pG4 step of [ d( TTAGGG)] 4 was found to be stabilized by the pi-pi stacking interaction of the porphyrin ring of TmPyP4 with the G4 quartet as well as the A3 bases of the G-quadruplex DNA. These findings provide novel insights for the design of porphyrin derivatives that bind to DNA with high affinity and specificity.