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 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'-ACAAATCCA-3'. Introduction of an indole linker greatly facilitated the synthesis of sequence-specific alkylating Py-Im polyamides.
Bando
Toshikazu
T
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8501, Japan.
Sasaki
Shunta
S
Minoshima
Masafumi
M
Dohno
Chikara
C
Shinohara
Ken-ichi
K
Narita
Akihiko
A
Sugiyama
Hiroshi
H
D000478:Alkylation; D020029:Base Pairing; D001483:Base Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D009757:Nylons / Q000737:chemistry; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry*
C506823:1,2,9,9a-tetrahydrocyclopropa(1,2-c)benz(1,2-e)indol-4-one; D003432:Cross-Linking Reagents; D003521:Cyclopropanes; D007093:Imidazoles; D007211:Indoles; D009757:Nylons; D009841:Oligonucleotides; D011758:Pyrroles; C029899:imidazole; C030374:indole; D004247:DNA