Interaction between GW2974 and telomeric G-quadruplex DNA: a possible anticancer mechanism

Elhaty I. A. M.

Chemical Papers, vol.75, no.12, pp.6323-6333, 2021 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 75 Issue: 12
  • Publication Date: 2021
  • Doi Number: 10.1007/s11696-021-01801-w
  • Journal Name: Chemical Papers
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core
  • Page Numbers: pp.6323-6333
  • Keywords: Telomere, Telomerase, Quadruplex, Cancer, GW2974
  • Istanbul Gelisim University Affiliated: Yes


Human telomere consists of tandem repeats of guanines; thus, it can form an intramolecular G-quadruplex structure, which can inhibit the telomerase enzyme that is found active in more than 85% of cancer cells. The present work investigated the interactions of GW2974, a quinazoline derivative with telomeric G-quadruplex AG3(TTAGGG)3. GW2974 had shown a good affinity to G-quadruplex DNA with a binding constant of 2.41 × 106 M−1 and melting temperature shift ΔTm of 9.9 °C. Increasing the GW2974 ratio with DNA up to five times showed an inverse effect on G-quadruplex DNA stability. The stoichiometric ratio between GW2974 and TelQ (per strand) was 2:1. Results obtained from absorption, fluorescence, and CD spectroscopic techniques indicated that GW2974 interacted with G-quadruplex through different binding modes. GW2974 showed good specificity to quadruplex over duplex DNA by 4.71-fold. These results indicated that stabilizing of telomeric G-quadruplex inhibited telomerase enzyme, which could be a potential anticancer mechanism of GW2974.