Targeting DNA G-Quadruplexes with Helical Small Molecules
Jena, Prakrit V
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Müller, S., Laxmi-Reddy, K., Jena, P. V., Baptiste, B., Dong, Z., Godde, F., Ha, T., et al. (2014). Targeting DNA G-Quadruplexes with Helical Small Molecules. ChemBioChem, 15 2563-2570. https://doi.org/10.1002/cbic.201402439
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 Förster 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.
DNA structures, foldamers, FRET, G-quadruplex, single-molecule fluorescence
We thank the “Cancer Research UK” for doctoral funding (SM) and “Association pour la recherche sur le cancer” for a postdoctoral fellowship (KLR). The Balasubramanian laboratory is core-funded by a programme grant from Cancer Research UK. TH acknowledges the NIH grant GM065367.
External DOI: https://doi.org/10.1002/cbic.201402439
This record's URL: https://www.repository.cam.ac.uk/handle/1810/246807
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/