Mirror-Image Dependence: Targeting Enantiomeric G-Quadruplex DNA Using Triplex Metallohelices

Angew Chem Int Ed Engl. 2018 Nov 26;57(48):15723-15727. doi: 10.1002/anie.201809207. Epub 2018 Nov 2.

Abstract

Natural d-DNA and l-DNA are mirror-image counterparts. However, because of the inherent flexibility and conformation diversity of DNA, it is still not clear how enantiomeric compounds recognize d-DNA and l-DNA. Herein, taking G-quadruplex (G4) DNA as an example that has diverse conformations and distinct biofunctions, the binding of ten pairs of iron triplex metallohelices to d- and l-G4 DNA were evaluated. The Δ-enantiomer binds to d-DNA and the Λ-enantiomer binds to l-DNA, exhibiting almost the same stabilization effect and binding affinity. The binding affinity of the Δ-metallohelix with d-G4 is nearly 70-fold higher than that of Λ-metallohelix binding d-G4. Δ-Metallohelix binding to d-G4 follows a two-step binding process driven by a favorable enthalpy contribution to compensate for the associated unfavorable entropy.

Keywords: DNA; chirality; helical structures; iron; supramolecular chemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • G-Quadruplexes
  • Kinetics
  • Molecular Structure
  • Organometallic Compounds / chemistry*
  • Thermodynamics

Substances

  • Organometallic Compounds
  • DNA