Excursions in polynuclear platinum DNA binding.

Excursions in polynuclear platinum DNA binding.
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DOI:
10.1039/c0cc01254h
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发表时间:
2010-09-28
期刊:
Chemical communications (Cambridge, England)
影响因子:
--
通讯作者:
Farrell NP
Farrell NP
中科院分区:
其他
文献类型:
--
作者:
Mangrum JB;Farrell NP

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多核铂类药物是一种结构独特的抗癌药物,与顺铂家族不同。为了描述这门课的化学和生物学,有必要挑战结构-活性关系的公认范式;设计新的化学型,描述其DNA结合模式的结构和后果。本文综述了共价(成键)和非共价(配体识别)加合物在DNA中引起的结构变化。溶液(核磁共振)、固态(晶体学)和气相(电喷雾电离质谱)技术以及分子生物学技术都被用来描述新的DNA结构。结合的方法允许分子描述迄今未观察到的加合物,如长距离主槽链间交联;DNA上的定向异构体和第三类配体- DNA结合,磷酸盐夹紧。磷酸盐识别不同于“经典的”小槽识别或嵌入。
Polynuclear platinum agents are a structurally unique class of anti-cancer drugs, distinct from the cisplatin family. To describe the chemistry and biology of this class, it was necessary to challenge the accepted paradigms for the structure–activity relationships; design new chemotypes and delineate the structures and consequences of their DNA binding modes. This article summarizes the structural changes induced in DNA by both covalent (bond-forming) and non-covalent (ligand recognition) adducts. Solution (Nuclear Magnetic Resonance), solid state (crystallography) and gas-phase (Electrospray Ionization Mass Spectrometry) techniques have all been used to describe the new DNA structures along with molecular biological techniques. The combined approaches allow molecular description of hitherto unobserved adducts such as long-range major-groove interstrand crosslinks; directional isomers on DNA and a third class of ligand–DNA binding, the phosphate clamp. The phosphate recognition is distinct from “classic” minor-groove recognition or intercalation.
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