title: Sequence-specific DNA alkylation by tandem Py-Im polyamide conjugates.
abstract: Tandem N-methylpyrrole-N-methylimidazole (Py-Im) polyamides with good sequence-specific DNA-alkylating activities have been designed and synthesized. Three alkylating tandem Py-Im polyamides with different linkers, which each contained the same moiety for the recognition of a 10 bp DNA sequence, were evaluated for their reactivity and selectivity by DNA alkylation, using high-resolution denaturing gel electrophoresis. All three conjugates displayed high reactivities for the target sequence. In particular, polyamide 1, which contained a β-alanine linker, displayed the most-selective sequence-specific alkylation towards the target 10 bp DNA sequence. The tandem Py-Im polyamide conjugates displayed greater sequence-specific DNA alkylation than conventional hairpin Py-Im polyamide conjugates (4 and 5). For further research, the design of tandem Py-Im polyamide conjugates could play an important role in targeting specific gene sequences.
authors.affiliation: Department of Chemistry, Kyoto University, Kitashirakawa-Oiwaketyo, Sakyo, Kyoto, 606-8502 (Japan), Fax: (+81) 75-753-3670.
authors.forename: Rhys Dylan
authors.initials: RD
authors.lastname: Taylor
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kawamoto
authors.forename: Kaori
authors.initials: K
authors.lastname: Hashiya
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D000478:Alkylation; D001483:Base Sequence; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009757:Nylons / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D004247:DNA; C096654:N-methylpyrrole; C018100:1-methylimidazole
keywords: DNA; alkylation; amides; conjugates; polymers