A minor groove binding copper-phenanthroline conjugate produces direct strand breaks via β-elimination of 2-deoxyribonolactone

被引：80

作者：

Bales, BC

Pitié, M

Meunier, B

Greenberg, MM

机构：

[1] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA

[2] CNRS, Chim Coordinat Lab, F-31077 Toulouse 4, France

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2002年 / 124卷 / 31期

关键词：

D O I：

10.1021/ja026970z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Copper-phenanthroline complexes and their conjugates are useful reagents for studying nucleic acid interactions. Although DNA cleavage by such complexes was discovered more than 20 years ago, significant questions remain unanswered regarding the chemical mechanism(s) by which DNA is damaged. Kinetic evidence is provided, which demonstrates that the major pathway for DNA damage by a minor groove binding molecule conjugated to copper phenanthroline (6) involves C1′-oxidation. Additional experiments using 6 and a DNA substrate containing 2-deoxyribonolactone (1) show that direct strand breaks are produced via β-elimination from 1. These studies support the original mechanism for DNA damage by copper phenanthroline put forth by Sigman and a more recent proposal concerning the mechanism for direct strand break formation. Copyright © 2002 American Chemical Society.

引用

收藏

页码：9062 / 9063

页数：2

相关论文

共 18 条

[1] CHEMICAL CONVERSION OF A DNA-BINDING PROTEIN INTO A SITE-SPECIFIC NUCLEASE [J].

CHEN, CHB ;

SIGMAN, DS .

SCIENCE, 1987, 237 (4819) :1197-1201

[2] Model studies indicate that copper phenanthroline induces direct strand breaks via β-elimination of the 2′-deoxyribonolactone intermediate observed in enediyne mediated DNA damage [J].

Chen, TQ ;

Greenberg, MM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1998, 120 (15) :3815-3816

[3] Thermodynamic consequences of an abasic lesion in duplex DNA are strongly dependent on base sequence [J].

Gelfand, CA ;

Plum, GE ;

Grollman, AP ;

Johnson, F ;

Breslauer, KJ .

BIOCHEMISTRY, 1998, 37 (20) :7321-7327

[4] NUCLEASE ACTIVITY OF 1,10-PHENANTHROLINE COPPER-ION - CHEMISTRY OF DEOXYRIBOSE OXIDATION [J].

GOYNE, TE ;

SIGMAN, DS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (09) :2846-2848

[5] Kinetics and stereoselectivity of thiol trapping of deoxyuridin-1′-yl in biopolymers and their relationship to the formation of premutagenic α-deoxynucleotides [J].

Hwang, JT ;

Greenberg, MM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (18) :4311-4315

[6] IDENTIFICATION OF 2-DEOXYRIBONOLACTONE AT THE SITE OF NEOCARZINOSTATIN-INDUCED CYTOSINE RELEASE IN THE SEQUENCE D(AGC) [J].

KAPPEN, LS ;

GOLDBERG, IH .

BIOCHEMISTRY, 1989, 28 (03) :1027-1032

[7] NUCLEASE ACTIVITY OF 1,10-PHENANTHROLINE COPPER-ION - REACTION WITH CGCGAATTCGCG AND ITS COMPLEXES WITH NETROPSIN AND ECORI [J].

KUWABARA, M ;

YOON, C ;

GOYNE, T ;

THEDERAHN, T ;

SIGMAN, DS .

BIOCHEMISTRY, 1986, 25 (23) :7401-7408

[8] CLEAVAGE OF DEOXYRIBONUCLEIC-ACID BY THE 1,10-PHENANTHROLINE-CUPROUS COMPLEX - HYDROGEN-PEROXIDE REQUIREMENT AND PRIMARY AND SECONDARY STRUCTURE SPECIFICITY [J].

MARSHALL, LE ;

GRAHAM, DR ;

REICH, KA ;

SIGMAN, DS .

BIOCHEMISTRY, 1981, 20 (02) :244-250

[9] Chemical mechanism of DNA scission by (1,10-phenanthroline)copper. Carbonyl oxygen of 5-methylenefuranone is derived from water [J].

Meijler, MM ;

Zelenko, O ;

Sigman, DS .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (05) :1135-1136

[10] Mechanism of DNA strand scission induced by (1,10-phenanthroline)copper complex:: Major direct DNA cleavage is not through 1′,2′-dehydronucleotide intermediate nor β-elimination of forming ribonolactone [J].

Oyoshi, T ;

Sugiyama, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (26) :6313-6314