Targeting DNA G-quadruplexes with helical small molecules

Sebastian Müller, Katta Laxmi-Reddy, Prakrit V. Jena, Benoit Baptiste, Zeyuan Dong, Frédéric Godde, Taekjip Ha, Raphaël Rodriguez, Shankar Balasubramanian, Ivan Huc

Research output: Contribution to journalArticlepeer-review

Abstract

We previously identified quinoline-based oligoamide helical foldamers and a trimeric macrocycle as selective ligands of DNA quadruplexes. Their helical structures might permit 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 might be a way to achieve sequence selective binding. Here, 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 by using FRET melting assay and singlemolecule FRET. Our results show that they constitute very potent ligands-comparable to the best so far reported. Their modes of interaction differ from those of traditional tetrad binders, thus opening avenues for the development of molecules specific for certain G-quadruplex conformations.

Original languageEnglish (US)
Pages (from-to)2563-2570
Number of pages8
JournalChemBioChem
Volume15
Issue number17
DOIs
StatePublished - Nov 24 2014

Keywords

  • DNA structures
  • FRET
  • Foldamers
  • G-quadruplex
  • Single-molecule fluorescence

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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