title: Ligand-Mediated G-Quadruplex Induction in a Double-Stranded DNA Context by Cyclic Imidazole/Lysine Polyamide.
abstract: G-quadruplex (G4) DNA is often observed as a DNA secondary structure in guanine-rich sequences, and is thought to be relevant to pharmacological and biological events. Therefore, G4 ligands have attracted great attention as potential anticancer therapies or in molecular probe applications. Here, we designed cyclic imidazole/lysine polyamide (cIKP) as a new class of G4 ligand. It was readily synthesized without time-consuming column chromatography. cIKP selectively recognized particular G4 structures with low nanomolar affinity. Moreover, cIKP exhibited the ability to induce G4 formation of the promoter of G4-containing DNA in the context of stable double-stranded DNA (dsDNA) under molecular crowding conditions. This cIKP might be applicable as a molecular probe for the detection of potential G4-forming sequences in dsDNA.
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Sefan
authors.initials: S
authors.lastname: Asamitsu
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan. bando@kuchem.kyoto-u.ac.jp.
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Bando
authors.affiliation: Department of Chemistry, Graduate School of Science, Kyoto University Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto, 606-8502, Japan. hs@kuchem.kyoto-u.ac.jp.|Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Yoshida-Ushinomiyacho, Sakyo-ku, Kyoto, 606-8501, Japan. hs@kuchem.kyoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
mesh_terms: D003500:Cyclization; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006801:Humans; D007093:Imidazoles; D008024:Ligands; D008239:Lysine; D015335:Molecular Probes / Q000138:chemical synthesis; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry; D011401:Promoter Regions, Genetic
chemical_list: D007093:Imidazoles; D008024:Ligands; D015335:Molecular Probes; D009757:Nylons; C029899:imidazole; D004247:DNA; D008239:Lysine
keywords: G-quadruplexes; G4 induction; cyclic polyamide; heterocycles; molecular crowding condition