9-[(10-(腺嘌呤-9-基)-4,8-二氮杂癸基)氨基]-6-氯-2-甲氧基吖啶在无嘌呤位点切割DNA。
9-[(10-(aden-9-yl)-4,8-diazadecyl)amino]-6-chloro-2-methoxy-acridine incises DNA at apurinic sites.
作者信息
Constant J F, O'Connor T R, Lhomme J, Laval J
机构信息
LEDSS (UA CNRS 332), Chimie Recherche, Université Scientifique et Médicale de Grenoble, Saint-Martin d'Heres, France.
出版信息
Nucleic Acids Res. 1988 Mar 25;16(6):2691-703. doi: 10.1093/nar/16.6.2691.
Abstract
The incision of DNA at apurinic/apyrimidinic sites (AP-sites) by chloro-6-methoxy-2 [(adenyl-9)-11)-4,8 diazadecyl]amino-9 acridine (Ade-Z-Acr), a 9-aminoacridine linked to an adenine, at nanomolar concentrations is described. Moreover, this drug, Ade-Z-Acr, is one of the most efficient drugs which cleaves DNA at AP-sites. The high activity is the result of the composition of the drug, since the individual components have no incising activity in the concentration range studied. The termini left by the Ade-Z-Acr molecule are a 3'deoxyribose and a 5'nucleotide. The termini and the inability of the Ade-Z-Acr to incise DNA with reduced AP-sites suggest that the mechanism of cleavage is beta-elimination.
摘要
描述了纳米摩尔浓度的氯-6-甲氧基-2-[(腺嘌呤-9)-11)-4,8-二氮杂癸基]氨基-9-吖啶（Ade-Z-Acr，一种与腺嘌呤相连的9-氨基吖啶）在无嘌呤/无嘧啶位点（AP位点）切割DNA的情况。此外，这种药物Ade-Z-Acr是在AP位点切割DNA最有效的药物之一。其高活性是药物组成的结果，因为在所研究的浓度范围内，各个组分没有切割活性。Ade-Z-Acr分子留下的末端是一个3'-脱氧核糖和一个5'-核苷酸。这些末端以及Ade-Z-Acr在AP位点减少时无法切割DNA的情况表明，切割机制是β-消除。
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本文引用的文献
1
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J Biol Chem. 1953 Aug;203(2):673-88.
2
Cleavage of DNA at apyrimidinic sites by lysyl-tryptophyl-alpha-lysine.赖氨酰-色氨酰-α-赖氨酸对无嘧啶位点处DNA的切割作用。
Biochem Biophys Res Commun. 1982 Apr 29;105(4):1433-9. doi: 10.1016/0006-291x(82)90948-2.
3
Antitumor activity, pharmacology, and toxicity of ellipticines, ellipticinium, and 9-hydroxy derivatives: preliminary clinical trials of 2-methyl-9-hydroxy ellipticinium (NSC 264-137).玫瑰树碱、玫瑰树碱盐及9-羟基衍生物的抗肿瘤活性、药理学及毒性：2-甲基-9-羟基玫瑰树碱盐（NSC 264-137）的初步临床试验
Recent Results Cancer Res. 1980;74:107-23. doi: 10.1007/978-3-642-81488-4_15.
4
Enzymology of DNA repair.DNA修复的酶学
IARC Sci Publ. 1980(27):55-73.
5
Specific nicking of DNA at apurinic sites by peptides containing aromatic residues.含芳香族残基的肽对脱嘌呤位点的DNA进行特异性切割。
J Biol Chem. 1981 Oct 25;256(20):10217-20.
6
Coding properties of poly(deoxycytidylic acid) templates containing uracil or apyrimidinic sites: in vitro modulation of mutagenesis by deoxyribonucleic acid repair enzymes.含有尿嘧啶或无嘧啶位点的聚（脱氧胞苷酸）模板的编码特性：脱氧核糖核酸修复酶对体外诱变的调节作用
Biochemistry. 1982 Dec 21;21(26):6746-51. doi: 10.1021/bi00269a020.
7
Mutagenicity and cytotoxicity of five antitumor ellipticines in mammalian cells and their structure-activity relationships in Salmonella.
Cancer Res. 1983 Aug;43(8):3544-52.
8
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9
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10
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