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Distinctive aspects of ligand binding to G4 DNA structure flanked by the double helix.

Distinctive aspects of ligand binding to G4 DNA structure flanked by the double helix.

Authors :
Tevonyan LL
Fatkullin TM
Beniaminov AD
Kaluzhny DN
Source :
Biochimie [Biochimie] 2025 Mar; Vol. 230, pp. 166-171. Date of Electronic Publication: 2024 Dec 17.
Publication Year :
2025

Abstract

Except for telomeres, G4 DNA structures in the human genome can be formed only within the context of double-stranded DNA. DNA duplexes flanking the G4 structure may potentially affect the G4 architecture and the binding of G4-specific ligands. Here, we examine the interaction of TMPyP4, NMM, and PDS ligands with three structures formed by the same DNA fragment containing the (GGGT) <subscript>4</subscript> sequence: the G4 in duplex (dsG4), G4 in single-stranded DNA (ssG4) and perfect duplex DNA (ds). To design a structure-specific fluorescent sensor, single thymine loops or proximal positions in DNA duplex were modified with FAM. Ligand-induced fluorescence quenching revealed a preferential binding of TMPyP4 and NMM with the dsG4 and ssG4 structures over the flanking duplex part or double-stranded DNA. PDS could not quench the fluorophores attached to single-nucleotide loops of the G4 DNA, although gel mobility assay confirmed tight binding of the ligand to the ssG4 or dsG4 structures. We hypothesize that the selectivity of the ligands for G4 loops compared to duplexes is responsible for the high quenching efficiency. Distinctive features of ligand interactions with G4 DNA in a duplex context suggest the potential for developing specific ligands for the genomic G4 structure.<br />Competing Interests: Conflict of interest We have no conflict of interest to declare.<br /> (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Details

Language :
English
ISSN :
1638-6183
Volume :
230
Database :
MEDLINE
Journal :
Biochimie
Publication Type :
Academic Journal
Accession number :
39674312
Full Text :
https://doi.org/10.1016/j.biochi.2024.12.005