ChemBioChem--Targeting DNA G-Quadruplexes with Helical Small Molecules
writer：Sebastian Müller,Katta Laxmi-Reddy, et al.
keywords：G-Quadruplex,Foldamers, DNA, FRET, single molecule fluorescence
source：期刊
specific source：ChemBioChem
Issue time：2014年
We previously identified quinoline-based oligoamide helical foldamers and a trimeric macrocycle as selective ligands of DNA quadruplexes. Their helical structure may permit the targeting of the backbone loops and grooves of G-quadruplexes instead of the G-tetrads. Given the vast array of morphologies G-quadruplex structures can adopt, this may be a way to elicit sequence selective binding. Herein, we describe the design and synthesis of molecules based on macrocyclic and helically folded oligoamides. We tested their ability to interact with the human telomeric G-quadruplex and an array of promoter G-quadruplexes using F?rster Resonance Energy Transfer (FRET) melting assay and single molecule FRET.
Our results show that they constitute very potent ligands, comparable to the best reported in the literature. Their mode of interaction differs from that of traditional tetrad binders, opening avenues for the development of molecules specific for certain G-quadruplex conformations.