Biomimetic, Smart, and Multivalent Ligands for G-Quadruplex Isolation and Bioorthogonal Imaging

ACS Chem Biol. 2021 May 21;16(5):905-914. doi: 10.1021/acschembio.1c00111. Epub 2021 Apr 29.

Abstract

G-quadruplexes (G4s) continue to gather wide attention in the field of chemical biology as their prevalence in the human genome and transcriptome strongly suggests that they play key regulatory roles in cell biology. G4-specific, cell-permeable small molecules (G4-ligands) innovatively permit the interrogation of cellular circuitries in order to assess to what extent G4s influence cell fate and functions. Here, we report on multivalent, biomimetic G4-ligands referred to as TASQs that enable both the isolation and visualization of G4s in human cells. Two biotinylated TASQs, BioTASQ and BioCyTASQ, are indeed efficient molecular tools to isolate G4s from mixtures of nucleic acids through simple affinity capture protocols and to image G4s in cells via a biotin/avidin pretargeted imaging system first applied here to G4s, found to be a reliable alternative to in situ click chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomimetic Materials / chemical synthesis*
  • Biomimetic Materials / isolation & purification*
  • Biotinylation
  • Cell Membrane Permeability
  • Click Chemistry
  • G-Quadruplexes
  • Humans
  • Ligands
  • MCF-7 Cells
  • Molecular Structure
  • Nucleic Acids / chemistry*
  • Optical Imaging

Substances

  • Ligands
  • Nucleic Acids