Specific adenine alkylation by pyrrole-imidazole CBI conjugates

被引：21

作者：

Bando, T ^{[1
]}

Narita, A ^{[1
]}

Sasaki, S ^{[1
]}

Sugiyama, H ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Sci, Dept Chem, Sakyo Ku, Kyoto 6068502, Japan

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2005年 / 127卷 / 40期

关键词：

D O I：

10.1021/ja052412j

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We examined DNA alkylation by pyrrole (Py)-imidazole (lm) hairpin polyamides, which possess 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) or cyclopropapyrroloindole (CPI) as DNA alkylating moieties. High-resolution denaturing gel electrophoresis revealed that alkylation by CBI conjugates 2 and 4 occurred specifically at adenines (A) in matched sequences, whereas CPI conjugates 1 and 3 alkylated both A and guanines (G) in matched sequences. The origin of the different reacitivity of CBI and CPI conjugates is discussed in relation to the electrophilicity of the cyclopropane moiety. The high selectivity of the CBI conjugate gives additional sequence specificity relative to CPI conjugates that would be useful for the biological applications.

引用

页码：13890 / 13895

页数：6

共 33 条

[1] A NOVEL PROPERTY OF DUOCARMYCIN AND ITS ANALOGS FOR COVALENT REACTION WITH DNA [J].

ASAI, A ;

NAGAMURA, S ;

SAITO, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (10) :4171-4177

[2]

Bando T, 2002, CHEM-EUR J, V8, P4781, DOI 10.1002/1521-3765(20021018)8:20<4781::AID-CHEM4781>3.0.CO

[3]

2-J

[4] Enantioselective DNA alkylation by a pyrrole-imidazole S-CIB conjugate [J].

Bando, T ;

Narita, A ;

Asada, K ;

Ayame, H ;

Sugiyama, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (29) :8948-8955

[5] Sequence specificity, reactivity, and antitumor activity of DNA-alkylating pyrrole-imidazole diamides [J].

Bando, T ;

Iida, H ;

Tao, ZF ;

Narita, A ;

Fukuda, N ;

Yamori, T ;

Sugiyama, H .

CHEMISTRY & BIOLOGY, 2003, 10 (08) :751-758

[6] C-H to N substitution dramatically alters the sequence-specific DNA alkylation, cytotoxicity, and expression of human cancer cell lines [J].

Bando, T ;

Narita, A ;

Iwai, A ;

Kihara, K ;

Sugiyama, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (11) :3406-3407

[7] Highly efficient sequence-specific DNA interstrand cross-linking by pyrrole/imidazole CPI conjugates [J].

Bando, T ;

Narita, A ;

Saito, I ;

Sugiyama, H .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2003, 125 (12) :3471-3485

[8] AN EFFICIENT SYNTHESIS OF 1,2,9,9A-TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL-4-ONE (CBI) - AN ENHANCED AND SIMPLIFIED ANALOG OF THE CC-1065 AND DUOCARMYCIN ALKYLATION SUBUNITS [J].

BOGER, DL ;

MCKIE, JA .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (05) :1271-1275

[9] SYNTHESIS OF N-(TERT-BUTYLOXYCARBONYL)-CBI, CBI, CBI-CDPI1, AND CBI-CDPI2 - ENHANCED FUNCTIONAL ANALOGS OF CC-1065 INCORPORATING THE 1,2,9,9A-TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL-4-ONE (CBI) LEFT-HAND SUBUNIT [J].

BOGER, DL ;

ISHIZAKI, T ;

KITOS, PA ;

SUNTORNWAT, O .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (23) :5823-5832

[10] SYNTHESIS AND PRELIMINARY EVALUATION OF AGENTS INCORPORATING THE PHARMACOPHORE OF THE DUOCARMYCIN PYRINDAMYCIN ALKYLATION SUBUNIT - IDENTIFICATION OF THE CC-1065 DUOCARMYCIN COMMON PHARMACOPHORE [J].

BOGER, DL ;

ISHIZAKI, T ;

ZARRINMAYEH, H ;

KITOS, PA ;

SUNTORNWAT, O .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (15) :4499-4502

← 1 2 3 4 →