Specific adenine alkylation by pyrrole-imidazole CBI conjugates.
We examined DNA alkylation by pyrrole (Py)-imidazole (Im) 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 reactivity 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.
Bando
Toshikazu
T
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan.
Narita
Akihiko
A
Sasaki
Shunta
S
Sugiyama
Hiroshi
H
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry*; D000478:Alkylation; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*
C506823:1,2,9,9a-tetrahydrocyclopropa(1,2-c)benz(1,2-e)indol-4-one; D003521:Cyclopropanes; D007093:Imidazoles; D007211:Indoles; D009757:Nylons; D011758:Pyrroles; C110747:cyclopropapyrroloindole; C029899:imidazole; D000225:Adenine