title: Specific adenine alkylation by pyrrole-imidazole CBI conjugates.
abstract: 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Akihiko
authors.initials: A
authors.lastname: Narita
authors.forename: Shunta
authors.initials: S
authors.lastname: Sasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: 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*
chemical_list: 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