Efficient DNA Alkylation by a Pyrrole-Imidazole CBI Conjugate with an Indole Linker:  Sequence-Specific Alkylation with Nine-Base-Pair Recognition

Conjugates 7, 8, and 10 of N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides and 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) with a 5-amino-1H-indole-2-carbonyl linker were synthesized by Fmoc solid-phase synthesis and a subsequent liquid-phase coupling procedure. The DNA a...

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Bibliographic Details
Published in:Bioconjugate chemistry 2006-05, Vol.17 (3), p.715-720
Main Authors: Bando, Toshikazu, Sasaki, Shunta, Minoshima, Masafumi, Dohno, Chikara, Shinohara, Ken-ichi, Narita, Akihiko, Sugiyama, Hiroshi
Format: Article
Language:English
Subjects:
Alkylation
Base Pairing
Base Sequence
Biochemistry
Carbonyl compounds
Cross-Linking Reagents - chemistry
Cyclopropanes - chemistry
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - genetics
DNA - metabolism
Imidazoles - chemistry
Indoles - chemistry
Nylons - chemistry
Oligonucleotides - chemistry
Oligonucleotides - metabolism
Polyamides
Pyrroles - chemistry
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Summary:Conjugates 7, 8, and 10 of N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides and 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) with a 5-amino-1H-indole-2-carbonyl linker were synthesized by Fmoc solid-phase synthesis and a subsequent liquid-phase coupling procedure. The DNA alkylating abilities of conjugates 7, 8, 6b, and 10 were examined using Texas Red-labeled PCR fragments and high-resolution denaturing gel electrophoresis. CBI conjugates 7 and 8 exhibited highly efficient sequence-specific DNA alkylation comparable with previous CBI conjugates with a vinyl linker. In particular, conjugate 10, with a 10-ringed hairpin Py-Im polyamide, alkylated at the adenine of 5‘-ACAAATCC A -3‘. Introduction of an indole linker greatly facilitated the synthesis of sequence-specific alkylating Py-Im polyamides.
ISSN:1043-1802
1520-4812
DOI:10.1021/bc060022w