Reversible manipulation of the G-quadruplex structures and enzymatic reactions through supramolecular host-guest interactions

Nucleic Acids Res. 2017 Mar 17;45(5):2283-2293. doi: 10.1093/nar/gkx025.

Abstract

Supramolecular chemistry addresses intermolecular forces and consequently promises great flexibility and precision. Biological systems are often the inspirations for supramolecular research. The G-quadruplex (G4) belongs to one of the most important secondary structures in nucleic acids. Until recently, the supramolecular manipulation of the G4 has not been reported. The present study is the first to disclose a supramolecular switch for the reversible control of human telomere G4s. Moreover, this supramolecular switch has been successfully used to manipulate an enzymatic reaction. Using various methods, we show that cucurbit[7]uril preferably locks and encapsulates the positively charged piperidines of Razo through supramolecular interactions. They can switch the conformations of the DNA inhibitor between a flexible state and the rigid G4 and are therefore responsible for the reversible control of the thrombin activity. Thus, our findings open a promising route and exhibit potential applications in future studies of chemical biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azo Compounds / chemistry
  • Base Sequence
  • Bridged-Ring Compounds / chemistry
  • Bridged-Ring Compounds / pharmacology*
  • DNA / chemistry*
  • G-Quadruplexes / drug effects*
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Molecular Docking Simulation
  • Piperidines / chemistry
  • Telomere / chemistry
  • Telomere / drug effects
  • Thrombin / chemistry*
  • Thrombin / metabolism

Substances

  • Azo Compounds
  • Bridged-Ring Compounds
  • Imidazoles
  • Piperidines
  • cucurbit(7)uril
  • DNA
  • Thrombin
  • azobenzene