Ligand-mediated G-quadruplex Induction in a Double-stranded DNA Context by Cyclic Imidazole/Lysine Polyamide

July 28, 2017

Title

Ligand-mediated G-quadruplex Induction in a Double-stranded DNA Context by Cyclic Imidazole/Lysine Polyamide

Author

Sefan Asamitsu, Yue Li, Toshikazu Bando, Hiroshi Sugiyama

Year

2016

Journal

A European Journal of Chemical Biology

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 regarding potential anticancer therapies or molecular probe applications. In the present study, we designed cyclic imidazole/lysine polyamide (cIKP) as a new class of G4 ligand, which was readily synthesized without time-consuming column chromatography. cIKP enables the selective recognition of particular G4 structures with low nanomolar affinity. Moreover, cIKP exhibited an unprecedented property: the induction of G4 formation on the promoter of G4-containing DNAs in a stable double-stranded DNA (dsDNA) context under molecular crowding conditions. This cIKP may be applicable as a molecular probe for the detection of potential G4-forming sequences in dsDNA.

Instrument

J-805

Keywords

Circular dichroism, DNA structure, Ligand binding, Nanostructures, Biochemistry