Common G-Quadruplex Binding Agents Found to Interact With i-Motif-Forming DNA: Unexpected Multi-Target-Directed Compounds.

Autor: Pagano A; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Iaccarino N; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Abdelhamid MAS; School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom., Brancaccio D; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Garzarella EU; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Di Porzio A; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Novellino E; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Waller ZAE; School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich, United Kingdom.; Centre for Molecular and Structural Biochemistry, University of East Anglia, Norwich Research Park, Norwich, United Kingdom., Pagano B; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Amato J; Department of Pharmacy, University of Naples Federico II, Naples, Italy., Randazzo A; Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Jazyk: angličtina
Zdroj: Frontiers in chemistry [Front Chem] 2018 Jul 24; Vol. 6, pp. 281. Date of Electronic Publication: 2018 Jul 24 (Print Publication: 2018).
DOI: 10.3389/fchem.2018.00281
Abstrakt: G-quadruplex (G4) and i-motif (iM) are four-stranded non-canonical nucleic acid structural arrangements. Recent evidences suggest that these DNA structures exist in living cells and could be involved in several cancer-related processes, thus representing an attractive target for anticancer drug discovery. Efforts toward the development of G4 targeting compounds have led to a number of effective bioactive ligands. Herein, employing several biophysical methodologies, we studied the ability of some well-known G4 ligands to interact with iM-forming DNA. The data showed that the investigated compounds are actually able to interact with both DNA in vitro , thus acting de facto as multi-target-directed agents. Interestingly, while all the compounds stabilize the G4, some of them significantly reduce the stability of the iM. The present study highlights the importance, when studying G4-targeting compounds, of evaluating also their behavior toward the i-motif counterpart.
Databáze: MEDLINE