MULTIPLE DNA-BINDING MODES OF ANTHRACENE-9-CARBONYL-N-1 SPERMINE

MULTIPLE DNA-BINDING MODES OF ANTHRACENE-9-CARBONYL-N-1 SPERMINE
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DOI:
10.1016/0968-0896(95)00086-v
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发表时间:
1995-06-01
影响因子:
3.5
通讯作者:
HAWORTH, IS
HAWORTH, IS
中科院分区:
医学3区
文献类型:
--
作者:
RODGER, A;TAYLOR, S;HAWORTH, IS

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用荧光光谱、线性二色性、圆二色性、正常吸收光谱(作为温度的函数)和计算机模拟研究了蒽-9-羰基-N-1-精胺(一种末端被蒽部分取代的精胺衍生物)的聚(dAdT)(2)配合物。为了比较,还提供了相同配体与聚(dGdC)(2)和小牛胸腺DNA的一些数据。在详细的荧光和CD光谱研究之后,我们提出蒽-9-羰基-N '-精胺以至少两种不同的结合方向与聚(dAdT)(2)嵌入。根据计算机模拟数据,我们推断配体可以从小沟和大沟插入。与此相反,插层与聚(dGdC),可能只发生在大沟。在高配体浓度下,CD光谱表明蒽-蒽相互作用,而LD数据指向沟槽结合的蒽。再次从计算机,我们提出了与这些意见相一致的结合模式。从LD光谱的其他数据表明,顺序的配体小牛胸腺DNA的结合,与GC丰富的网站被占领的第一。在低配体浓度下,9-羰基-N-1-精胺能够稳定聚(dAdT)(2),防止热分解,但不如精胺有效。小牛胸腺DNA的情况正好相反。聚(dAdT)(2)的蒽-9-羰基-N-1-精胺和精胺复合物在其熔融曲线中都显示出熔融前转变。蒽-9-羰基-N-1-精胺与聚(dAdT)(2)的复合物也显示出熔融后转变。
The poly(dAdT)(2) complex of anthracene-9-carbonyl-N-1-spermine, a spermine derivative terminally substituted with an anthracene moiety, has been studied using fluorescence, linear dichroism, circular dichroism, normal absorption spectroscopy (as a function of temperature) and computer modelling. For comparison, some data are also provided for the same ligand with poly(dGdC)(2) and calf thymus DNA. Following detailed fluorescence and CD spectroscopic studies, we propose that anthracene-9-carbonyl-N'-spermine intercalates in at least two different binding orientations with poly(dAdT)(2). Based on computer simulation data, we deduce that the ligand can intercalate from both the minor groove and the major groove. In contrast, intercalation with poly(dGdC), probably occurs only from the major groove. At high ligand concentrations, the CD spectra suggest anthracene-anthracene interactions, whilst the LD data point towards a groove-bound anthracene. Again from computer we propose binding modes consistent with these observations. Other data from the LD spectra suggest a sequential to the binding of the ligand to calf thymus DNA, with GC-rich sites being occupied first. At low ligand concentrations, 9-carbonyl-N-1-spermine is able to stabilize poly(dAdT)(2) against thermal decomposition, but not as effectively as spermine. The reverse is found to be true with calf thymus DNA. Both the anthracene-9-carbonyl-N-1-spermine and spermine complexes of poly(dAdT)(2) show pre-melt transitions in their melting curves. The anthracene-9-carbonyl-N-1-spermine complex with poly(dAdT)(2) also shows a post-melt transition.