title: Sequence-specific alkylation by Y-shaped and tandem hairpin pyrrole-imidazole polyamides.
abstract: To extend the target DNA sequence length of the hairpin pyrrole-imidazole (Py-Im) polyamide 1, we designed and synthesized Y-shaped and tandem hairpin Py-Im polyamides 2 and 3, which possess 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) as DNA-alkylating moieties. High-resolution denaturing polyacrylamide gel electrophoresis by using 5'-Texas-Red-labeled 465 base pair (bp) DNA fragments revealed that conjugates 2 and 3 alkylated the adenine of the target DNA sequences at nanomolar concentrations. Conjugate 2 alkylated adenine N3 at the 3' end of two 8 bp match sequences, 5'-AATAACCA-3' (site A) and 5'-AAATTCCA-3' (site C), while conjugate 3 recognized one 10 bp match sequence, 5'-AGAATAACCA-3' (site A) in the 465 bp DNA fragments. These results demonstrate that seco-CBI conjugates of Y-shaped and tandem hairpin polyamides have extended their target alkylation sequences.
authors.affiliation: Department of Chemistry, Kyoto University, Kitashirakawa-Oiwaketyo, Sakyo, Kyoto, 606-8502, Japan.
authors.forename: Shunta
authors.initials: S
authors.lastname: Sasaki
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Masafumi
authors.initials: M
authors.lastname: Minoshima
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Shinohara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama