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放线菌素D与寡核苷酸形成复合物,作为该药物与DNA结合的模型。对药物-核酸复合物进行顺磁诱导弛豫实验。

Actinomycin D complexes with oligonucleotides as models for the binding of the drug to DNA. Paramagnetic induced relaxation experiments on drug-nucleic acid complexes.

作者信息

Chiao Y C, Krugh T R

出版信息

Biochemistry. 1977 Feb 22;16(4):747-55. doi: 10.1021/bi00623a029.

DOI:10.1021/bi00623a029
PMID:189809
Abstract

Mn(II) ions have been used as a paramagnetic probe to investigate the geometry of drug-oligonucleotide complexes. Nuclear magnetic resonance and electron spin resonance experiments show that Mn(II) ions bind approximately two orders of magnitude stronger to the 5'-terminal phosphate group than to the 3'-5' phosphodiester linkage of deoxydinucleotides. By using mixtures of nucleotides in which only one nucleotide contains a terminal phosphate group, the location of the Mn(II) ion in the drug-nucleotide-Mn(II) complexes may be preselected. The paramagnetic induced relaxation of the nuclear spin systems in these complexes has been used to investigate the geometry of these complexes. These data confirm that actinomycin D is able to recognize and preferentially bind guanine (as opposed to adenine) nucleotides in the quinoid portion of the phenoxazone ring, while both adenine and guanine will bind to the benzenoid portion of the phenoxazone ring. These results suggest that stacking forces are primarily responsible for the general requirement of a guanine base when actinomycin D binds to DNA.

摘要

锰(II)离子已被用作顺磁探针来研究药物 - 寡核苷酸复合物的几何结构。核磁共振和电子自旋共振实验表明,锰(II)离子与脱氧二核苷酸的5'-末端磷酸基团的结合力比与3'-5'磷酸二酯键的结合力强约两个数量级。通过使用仅一种核苷酸含有末端磷酸基团的核苷酸混合物,可以预先选择锰(II)离子在药物 - 核苷酸 - 锰(II)复合物中的位置。这些复合物中核自旋系统的顺磁诱导弛豫已被用于研究这些复合物的几何结构。这些数据证实,放线菌素D能够识别并优先结合吩恶嗪环醌型部分中的鸟嘌呤(与腺嘌呤相对)核苷酸,而腺嘌呤和鸟嘌呤都会结合到吩恶嗪环的苯型部分。这些结果表明,当放线菌素D与DNA结合时,堆积力是对鸟嘌呤碱基一般要求的主要原因。

相似文献

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Actinomycin D complexes with oligonucleotides as models for the binding of the drug to DNA. Paramagnetic induced relaxation experiments on drug-nucleic acid complexes.放线菌素D与寡核苷酸形成复合物,作为该药物与DNA结合的模型。对药物-核酸复合物进行顺磁诱导弛豫实验。
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引用本文的文献

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Nucleic Acids Res. 2003 Aug 15;31(16):e98. doi: 10.1093/nar/gng100.
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Structure-affinity relationships for the binding of actinomycin D to DNA.放线菌素D与DNA结合的结构-亲和力关系。
J Comput Aided Mol Des. 1997 Mar;11(2):114-28. doi: 10.1023/a:1008018106064.
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Photoaffinity approaches to determining the sequence selectivities of DNA-small molecule interactions: actinomycin D and ethidium.
用于确定DNA-小分子相互作用序列选择性的光亲和方法:放线菌素D和溴化乙锭。
Nucleic Acids Res. 1995 Apr 11;23(7):1252-9. doi: 10.1093/nar/23.7.1252.
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Spectroscopic properties of ethidium monoazide: a fluorescent photoaffinity label for nucleic acids.单叠氮溴化乙锭的光谱性质:一种用于核酸的荧光光亲和标记物。
Nucleic Acids Res. 1978 Dec;5(12):4891-903. doi: 10.1093/nar/5.12.4891.