title: Binding of hairpin pyrrole and imidazole polyamides to DNA: relationship between torsion angle and association rate constants.
abstract: N-methylpyrrole (Py)-N-methylimidazole (Im) polyamides are small organic molecules that bind to DNA with sequence specificity and can be used as synthetic DNA-binding ligands. In this study, five hairpin eight-ring Py-Im polyamides 1-5 with different number of Im rings were synthesized, and their binding behaviour was investigated with surface plasmon resonance assay. It was found that association rate (k(a)) of the Py-Im polyamides with their target DNA decreased with the number of Im in the Py-Im polyamides. The structures of four-ring Py-Im polyamides derived from density functional theory revealed that the dihedral angle of the Py amide carbonyl is 14∼18°, whereas that of the Im is significantly smaller. As the minor groove of DNA has a helical structure, planar Py-Im polyamides need to change their conformation to fit it upon binding to the minor groove. The data explain that an increase in planarity of Py-Im polyamide induced by the incorporation of Im reduces the association rate of Py-Im polyamides. This fundamental knowledge of the binding of Py-Im polyamides to DNA will facilitate the design of hairpin Py-Im polyamides as synthetic DNA-binding modules.
authors.affiliation: Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Yoshida Honmachi, Sakyo, Kyoto 606-8501, Japan. han.yongwoon.4u@kyoto-u.ac.jp
authors.forename: Yong-Woon
authors.initials: YW
authors.lastname: Han
authors.forename: Tomoko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Yokota
authors.forename: Gengo
authors.initials: G
authors.lastname: Kashiwazaki
authors.forename: Hironobu
authors.initials: H
authors.lastname: Morinaga
authors.forename: Kaori
authors.initials: K
authors.lastname: Hashiya
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Harada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D004247:DNA / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry*; D011758:Pyrroles / Q000737:chemistry*; D020349:Surface Plasmon Resonance; D054159:Torsion, Mechanical
chemical_list: D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D004247:DNA