Bioorganic & Medicinal Chemistry 2010-12-01

Bisaryldiketene derivatives: A new class of selective ligands for c-myc G-quadruplex DNA.

Dan Peng, Jia-Heng Tan, Shuo-Bin Chen, Tian-Miao Ou, Lian-Quan Gu, Zhi-Shu Huang

Index: Bioorg. Med. Chem. 18(23) , 8235-42, (2010)

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Abstract

A series of bisaryldiketene derivatives were designed and synthesized as a new class of specific G-quadruplex ligands. The ligand-quadruplex interactions were further evaluated by FRET, ITC, and PCR stop assay. In contrast to most of the G-quadruplex ligands reported so far, which comprise an extended aromatic ring, these compounds are neither polycyclic nor macrocyclic, but have a non-aromatic and relative flexible linker between two quinoline moieties enabling the conformation of compounds to be flexible. Our results showed that these bisaryldiketene derivatives could selectively recognize G-quadruplex DNA rather than binding to duplex DNA. Moreover, they showed promising discrimination between different G-quadruplex DNA. The primary binding affinity of ligand M2 for c-myc G-quadruplex DNA was over 200 times larger than that for telomere G-quadruplex DNA.Copyright © 2010 Elsevier Ltd. All rights reserved.