The chiral potential of phenanthriplatin and its influence on guanine binding.
The chiral potential of phenanthriplatin and its influence on guanine binding.
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DOI：
10.1021/ja4125115
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发表时间：
2014-02-05
影响因子：
15
通讯作者：
Lippard SJ
中科院分区：
文献类型：
--
作者：
Johnstone TC;Lippard SJ
单官能铂配合物cis-[Pt(NH3)2Cl(Am)]+，也被称为苯三铂，其中Am是N-杂环基菲咯啶，具有良好的抗癌活性。与顺铂等双功能化合物不同，苯三铂只能与DNA形成一个共价键。另一个显著特征是苯三铂是手性的。围绕菲啶配体的铂-N键的旋转使配合物外消旋，问题是这一过程在生理条件下是否足够慢，从而影响其与DNA的结合性能。本文介绍了非对映异构体苯三铂类似物的核磁共振波谱、X-射线结晶学、分子动力学和密度泛函理论研究结果，以探讨苯三铂的内部动力学。这些结果表明，苯三铂在生理条件下会迅速外消旋。这些信息也有助于解释小分子模型的苯三铂-铂DNA的核磁共振谱。除其他外，这些研究表明，一种非对映异构体形式的络合物顺式-[铂(NH3)2(Am)(R-Gua)]2+，其中R-Gua是9-甲基或9-乙基鸟嘌呤，其来源是铂鸟嘌呤碱的羰基氧与顺式配位胺之间的分子内相互作用。这一发现与苯三铂的DNA损伤特性及其生物活性的相关性进行了讨论。
The monofunctional platinum complex cis-[Pt(NH3)2Cl(Am)]+, also known as phenanthriplatin, where Am is the N-heterocyclic base phenanthridine, has promising anticancer activity. Unlike bifunctional compounds such as cisplatin, phenanthriplatin can form only one covalent bond to DNA. Another distinguishing feature is that phenanthriplatin is chiral. Rotation about the Pt–N bond of the phenanthridine ligand racemizes the complex, and the question arises as to whether this process is sufficiently slow under physiological conditions to impact its DNA-binding properties. Here we present the results of NMR spectroscopic, X-ray crystallographic, molecular dynamics, and density functional theoretical investigations of diastereomeric phenanthriplatin analogs in order to probe the internal dynamics of phenanthriplatin. These results reveal that phenanthriplatin rapidly racemizes under physiological conditions. The information also facilitated the interpretation of the NMR spectra of small molecule models of phenanthriplatin-platinated DNA. These studies indicate, inter alia, that one diastereomeric form of the complexes cis-[Pt(NH3)2(Am)(R-Gua)]2+, where R-Gua is 9-methyl- or 9-ethylguanine, is preferred over the other, the origin of which stems from an intramolecular interaction between the carbonyl oxygen of the platinated guanine base and a cis-coordinated ammine. The relevance of this finding to the DNA-damaging properties of phenanthriplatin and its biological activity is discussed.
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DOI：
10.1016/s0020-1693(00)80051-1
发表时间：
1984-01-01
期刊：
INORGANICA CHIMICA ACTA-BIOINORGANIC CHEMISTRY
影响因子：
--
作者：
BRUCK, MA;BAU, R;KIDANI, Y
通讯作者：
KIDANI, Y
影响因子：
4.6
作者：
Johnstone TC;Wilson JJ;Lippard SJ
通讯作者：
Lippard SJ
影响因子：
5.7
作者：
Lovejoy KS;Serova M;Bieche I;Emami S;D'Incalci M;Broggini M;Erba E;Gespach C;Cvitkovic E;Faivre S;Raymond E;Lippard SJ
通讯作者：
Lippard SJ
影响因子：
2
作者：
Bain, AD;Rex, DM;Smith, RN
通讯作者：
Smith, RN
DOI：
10.1039/c29710000656
发表时间：
1971-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY D-CHEMICAL COMMUNICATIONS
影响因子：
--
作者：
KOST, D;CARLSON, EH;RABAN, M
通讯作者：
RABAN, M