Polycyclic aromatic DNA-Base surrogates: High-affinity binding to an adenine-specific base-flipping DNA methyltransferase

被引：73

作者：

Beuck, C

Singh, I

Bhattacharya, A

Heckler, W

Parmar, VS

Seitz, O

Weinhold, E

机构：

[1] Humboldt Univ, Inst Chem, D-12489 Berlin, Germany

[2] Rhein Westfal TH Aachen, Inst Organ Chem, D-52056 Aachen, Germany

[3] Max Planck Inst Mol Physiol, D-44227 Dortmund, Germany

[4] Univ Delhi, Dept Chem, Bioorgan Lab, Delhi 110007, India

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2003年 / 42卷 / 33期

关键词：

abasic sites; DNA methylation; DNA-protein interactions; enzymes; glycosides; nucleic acids;

D O I：

10.1002/anie.200219972

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Filling the hole is a strategy that confers high-affinity DNA binding to the M·TaqI DNA methyltransferase. Aromatic base surrogates (e.g. pyrene, red in picture) were introduced into DNA by means of organocuprate-mediated C-glycosylations. A new competitive binding assay revealed that DNA with aromatic base surrogates placed opposite to the target base binds to M·TaqI with up to 400-fold-enhanced affinity.

引用

页码：3958 / 3960

页数：3

共 17 条

[1] SYNTHESIS OF C-GLUCOSIDES BY REACTIONS OF GLUCOSYL HALIDES WITH ORGANOCUPRATES
BIHOVSKY, R
SELICK, C
GIUSTI, I
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1988, 53 (17) : 4026 - 4031
[2] AdoMet-dependent methylation, DNA methyltransferases and base flipping
Cheng, XD
Roberts, RJ
[J]. NUCLEIC ACIDS RESEARCH, 2001, 29 (18) : 3784 - 3795
[3] CHENG XD, 1995, ANNU REV BIOPH BIOM, V24, P293, DOI 10.1146/annurev.bb.24.060195.001453
[4] Structure of the N6-adenine DNA methyltransferase M•Taql in complex with DNA and a cofactor analog
Goedecke, K
Pignot, M
Goody, RS
Scheidig, AJ
Weinhold, E
[J]. NATURE STRUCTURAL BIOLOGY, 2001, 8 (02) : 121 - 125
[5] An essential role for DNA adenine methylation in bacterial virulence
Heithoff, DM
Sinsheimer, RL
Low, DA
Mahan, MJ
[J]. SCIENCE, 1999, 284 (5416) : 967 - 970
[6] ALPHA-THYMIDIN
HOFFER, M
[J]. CHEMISCHE BERICHTE-RECUEIL, 1960, 93 (12): : 2777 - 2781
[7] 2-Aminopurine as a fluorescent probe for DNA base flipping by methyltransferases
Holz, B
Klimasauskas, S
Serva, S
Weinhold, E
[J]. NUCLEIC ACIDS RESEARCH, 1998, 26 (04) : 1076 - 1083
[8] Jeltsch A, 2002, CHEMBIOCHEM, V3, P275, DOI 10.1002/1439-7633(20020402)3:4<274::AID-CBIC274>3.0.CO
[9] 2-S
[10] Base-flipping mutations of uracil DNA glycosylase: substrate rescue using a pyrene nucleotide wedge
Jiang, YL
Stivers, JT
Song, FH
[J]. BIOCHEMISTRY, 2002, 41 (37) : 11248 - 11254

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