Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (Zebularine) at the G(C)under-barGC recognition domain

被引：16

作者：

Marquez, VE

Eritja, R

Kelley, JA

Vanbemmel, D

Christman, J

机构：

[1] NCI, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA

[2] CSIC, Ctr Invest & Desarrollo, E-08034 Barcelona, Spain

[3] Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA

[4] Univ Nebraska, Coll Med, Eppley Canc Ctr, Omaha, NE 68198 USA

来源：

THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS | 2003年 / 1002卷

关键词：

DNA methyltransferase; methylation inhibitor; cytidine deaminase; inhibitor; 2-(1H)-pyrimidinone; 5-azacytosine; zebularine; 5-azacytidine; 2'-deoxy-5-azacytidine; gene reactivation;

D O I：

10.1196/annals.1281.014

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

A short oligodeoxynucleotide (ODN) with 2-(1H)-pyrimidinone at the HhaI DNA methyltransferase target site (GCGC) is shown to induce a level of inhibition of methyl transfer and thermal stability of the complex with the enzyme identical to that achieved with a similar ODN substituted with 5-azacytosine. The drugs responsible for these effects-zebularine and 5-azacytidine/2'-deoxy-5-azacytidine-are contrasted in terms of chemical stability and possible metabolic activation by a brief structure-activity analysis.

引用

收藏

页码：154 / 164

页数：11

相关论文

共 41 条

[1] INHIBITION OF CYTIDINE DEAMINASE BY DERIVATIVES OF 1-(BETA-D-RIBOFURANOSYL)-DIHYDROPYRIMIDIN-2-ONE (ZEBULARINE) [J].

BARCHI, JJ ;

HACES, A ;

MARQUEZ, VE ;

MCCORMACK, JJ .

NUCLEOSIDES & NUCLEOTIDES, 1992, 11 (10) :1781-1793

[2] THE DECOMPOSITION OF 1-(BETA-D-RIBOFURANOSYL)-1,2-DIHYDROPYRIMIDIN-2-ONE (ZEBULARINE) IN ALKALI - MECHANISM AND PRODUCTS [J].

BARCHI, JJ ;

MUSSER, S ;

MARQUEZ, VE .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (02) :536-541

[3] ISOLATION, CHARACTERIZATION, AND PROPERTIES OF A LABILE HYDROLYSIS PRODUCT OF ANTI-TUMOR NUCLEOSIDE, 5-AZACYTIDINE [J].

BEISLER, JA .

JOURNAL OF MEDICINAL CHEMISTRY, 1978, 21 (02) :204-208

[4] CYTIDINE DEAMINASE - THE 2-CENTER-DOT-3-ANGSTROM CRYSTAL-STRUCTURE OF AN ENZYME - TRANSITION-STATE ANALOG COMPLEX [J].

BETTS, L ;

XIANG, SB ;

SHORT, SA ;

WOLFENDEN, R ;

CARTER, CW .

JOURNAL OF MOLECULAR BIOLOGY, 1994, 235 (02) :635-656

[5] Inhibition of HhaI DNA (cytosine-C5) methyltransferase by oligodeoxyribonucleotides containing 5-aza-2′-deoxycytidine:: Examination of the intertwined roles of co-factor, target, transition state structure and enzyme conformation [J].

Brank, AS ;

Eritja, R ;

Garcia, RG ;

Marquez, VE ;

Christman, JK .

JOURNAL OF MOLECULAR BIOLOGY, 2002, 323 (01) :53-67

[6] NUCLEIC-ACID COMPONENTS AND THEIR ANALOGS .190. PREPARATION OF 2-PYRIMIDINONE NUCLEOSIDES FROM URACIL NUCLEOSIDES [J].

CECH, D ;

HOLY, A .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1977, 42 (07) :2246-2260

[7] Inhibition of DNA methylation and reactivation of silenced genes by zebularine [J].

Cheng, JC ;

Matsen, CB ;

Gonzales, FA ;

Ye, W ;

Greer, S ;

Marquez, VE ;

Jones, PA ;

Selker, EU .

JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (05) :399-409

[8] ANTITUMOR PROPERTIES OF 2(1H)-PYRIMIDINONE RIBOSIDE (ZEBULARINE) AND ITS FLUORINATED ANALOGS [J].

DRISCOLL, JS ;

MARQUEZ, VE ;

PLOWMAN, J ;

LIU, PS ;

KELLEY, JA ;

BARCHI, JJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (11) :3280-3284

[9] EFFECTS OF COFACTOR AND DEOXYCYTIDINE SUBSTITUTED OLIGONUCLEOTIDES UPON SEQUENCE-SPECIFIC INTERACTIONS BETWEEN MSPI DNA METHYLTRANSFERASE AND DNA [J].

FORD, K ;

TAYLOR, C ;

CONNOLLY, B ;

HORNBY, DP .

JOURNAL OF MOLECULAR BIOLOGY, 1993, 230 (03) :779-786

[10] BINDING OF PYRIMIDIN-2-ONE RIBONUCLEOSIDE BY CYTIDINE DEAMINASE AS THE TRANSITION-STATE ANALOG 3,4-DIHYDROURIDINE AND THE CONTRIBUTION OF THE 4-HYDROXYL GROUP TO ITS BINDING-AFFINITY [J].

FRICK, L ;

YANG, C ;

MARQUEZ, VE ;

WOLFENDEN, R .

BIOCHEMISTRY, 1989, 28 (24) :9423-9430

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