A Selective G-Quadruplex DNA-Stabilizing Ligand Based on a Cyclic Naphthalene Diimide Derivative

Md. Monirul Islam; Satoshi Fujii; Shinobu Sato; Tatsuo Okauchi; Shigeori Takenaka

doi:10.3390/molecules200610963

Molecules (Jun 2015)

A Selective G-Quadruplex DNA-Stabilizing Ligand Based on a Cyclic Naphthalene Diimide Derivative

Md. Monirul Islam,
Satoshi Fujii,
Shinobu Sato,
Tatsuo Okauchi,
Shigeori Takenaka

Affiliations

Md. Monirul Islam: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan
Satoshi Fujii: Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka 820-8502, Japan
Shinobu Sato: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan
Tatsuo Okauchi: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan
Shigeori Takenaka: Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804-8550, Japan

DOI: https://doi.org/10.3390/molecules200610963
Journal volume & issue: Vol. 20, no. 6
pp. 10963 – 10979

Abstract

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A cyclic naphthalene diimide (cyclic NDI, 1), carrying a benzene moiety as linker chain, was synthesized and its interaction with G-quadruplex DNAs of a-core and a-coreTT as a human telomeric DNA, c-kit and c-myc as DNA sequence at promoter region, or thrombin-binding aptamer (TBA) studied based on UV-VIS and circular dichroism (CD) spectroscopic techniques, thermal melting temperature measurement, and FRET-melting assay. The circular dichroism spectra showed that 1 induced the formation of different types of G-quadruplex DNA structure. Compound 1 bound to these G-quadruplexes with affinities in the range of 106–107 M−1 order and a 2:1 stoichiometry. Compound 1 showed 270-fold higher selectivity for a-core than dsDNA with a preferable a-core binding than a-coreTT, c-kit, c-myc and TBA in the presence of K+, which is supported by thermal melting studies. The FRET-melting assay also showed that 1 bound preferentially to human telomeric DNA. Compound 1 showed potent inhibition against telomerase activity with an IC50 value of 0.9 μM and preferable binding to G-quadruplexes DNA than our previously published cyclic NDI derivative 3 carrying a benzene moiety as longer linker chain.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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