Methyltransferase-directed DNA strand scission

被引：30

作者：

Comstock, LR ^{[1
]}

Rajski, SR ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Pharm, Madison, WI 53705 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2005年 / 127卷 / 41期

关键词：

D O I：

10.1021/ja054128y

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We demonstrate here that MTase-modified DNA can undergo the Staudinger ligation with triarylphosphines derivatized with phenanthroline. Presentation of these duplexes with Cu(II) and 3-mercaptopropionic acid leads to strand scission proximal to the MTase recognition site. By virtue of their ability to use a synthetic azide-bearing cofactor, M.TaqI and M.HhaI produce a DNA lesion that induces scission 5′ to the base modified by the enzyme. This chemistry represents a new approach by which regions of DNA methylation can be rapidly identified on the basis of DNA damage. Copyright © 2005 American Chemical Society.

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页码：14136 / 14137

页数：2

相关论文

共 11 条

[1] NUCLEASE ACTIVITY OF 1,10-PHENANTHROLINE COPPER - SEQUENCE-SPECIFIC TARGETING [J].

CHEN, CHB ;

SIGMAN, DS .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (19) :7147-7151

[2] Conversion of DNA methyltransferases into azidonucleosidyl transferases via synthetic cofactors [J].

Comstock, LR ;

Rajski, SR .

NUCLEIC ACIDS RESEARCH, 2005, 33 (05) :1644-1652

[3] Efficient synthesis of azide-bearing cofactor mimics [J].

Comstock, LR ;

Rajski, SR .

JOURNAL OF ORGANIC CHEMISTRY, 2004, 69 (04) :1425-1428

[4] Optimizing the targeted chemical nuclease activity of 1,10-phenanthroline-copper by ligand modification [J].

Gallagher, J ;

Chen, CB ;

Pan, CQ ;

Perrin, DM ;

Cho, YM ;

Sigman, DS .

BIOCONJUGATE CHEMISTRY, 1996, 7 (04) :413-420

[5] Design of site specific DNA damaging agents for generation of multiply damaged sites [J].

Martelli, A ;

Constant, JF ;

Demeunynck, M ;

Lhomme, J ;

Dumy, P .

TETRAHEDRON, 2002, 58 (21) :4291-4298

[6] PROCARYOTIC AND EUKARYOTIC TRAITS OF DNA METHYLATION IN SPIROPLASMAS (MYCOPLASMAS) [J].

NUR, I ;

SZYF, M ;

RAZIN, A ;

GLASER, G ;

ROTTEM, S ;

RAZIN, S .

JOURNAL OF BACTERIOLOGY, 1985, 164 (01) :19-24

[7] Oxidative strand scission of nucleic acids: Routes initiated by hydrogen abstraction from the sugar moiety [J].

Pogozelski, WK ;

Tullius, TD .

CHEMICAL REVIEWS, 1998, 98 (03) :1089-1107

[8] DEGRADATION OF DEOXYRIBONUCLEIC-ACID BY A 1,10-PHENANTHROLINE-COPPER COMPLEX - THE ROLE OF HYDROXYL RADICALS [J].

QUE, BG ;

DOWNEY, KM ;

SO, AG .

BIOCHEMISTRY, 1980, 19 (26) :5987-5991

[9] MODE OF ACTION OF THE SPIROPLASMA CPG METHYLASE MSSSI [J].

RENBAUM, P ;

RAZIN, A .

FEBS LETTERS, 1992, 313 (03) :243-247

[10] Conversion of aryl azides to O-alkyl Imidates via modified staudinger ligation [J].

Restituyo, JA ;

Comstock, LR ;

Petersen, SG ;

Stringfellow, T ;

Rajski, SR .

ORGANIC LETTERS, 2003, 5 (23) :4357-4360