Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology

The involvement of G-quadruplex (G4) structures in nucleic acids in various molecular processes in cells such as replication, gene-pausing, the expression of crucial cancer-related genes and DNA damage repair is well known. The compounds targeting G4 usually bind directly to the G4 structure, but so...

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Main Authors: Lukáš Trizna, Ladislav Janovec, Andrea Halaganová, Viktor Víglaský
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/14/7639
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author Lukáš Trizna
Ladislav Janovec
Andrea Halaganová
Viktor Víglaský
author_facet Lukáš Trizna
Ladislav Janovec
Andrea Halaganová
Viktor Víglaský
author_sort Lukáš Trizna
collection DOAJ
description The involvement of G-quadruplex (G4) structures in nucleic acids in various molecular processes in cells such as replication, gene-pausing, the expression of crucial cancer-related genes and DNA damage repair is well known. The compounds targeting G4 usually bind directly to the G4 structure, but some ligands can also facilitate the G4 folding of unfolded G-rich sequences and stabilize them even without the presence of monovalent ions such as sodium or potassium. Interestingly, some G4-ligand complexes can show a clear induced CD signal, a feature which is indirect proof of the ligand interaction. Based on the dichroic spectral profile it is not only possible to confirm the presence of a G4 structure but also to determine its topology. In this study we examine the potential of the commercially available Rhodamine 6G (RhG) as a G4 ligand. RhG tends to convert antiparallel G4 structures to parallel forms in a manner similar to that of Thiazole Orange. Our results confirm the very high selectivity of this ligand to the G4 structure. Moreover, the parallel topology of G4 can be verified unambiguously based on the specific induced CD profile of the G4-RhG complex. This feature has been verified on more than 50 different DNA sequences forming various non-canonical structural motifs.
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spelling doaj.art-03f0f273f5fa4ec198ea33471a6c56862023-11-22T04:01:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214763910.3390/ijms22147639Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and TopologyLukáš Trizna0Ladislav Janovec1Andrea Halaganová2Viktor Víglaský3Department of Biochemistry, Institute of Chemistry, Faculty of Sciences, Pavol Jozef Šafárik University, 04001 Košice, SlovakiaDepartment of Organic Chemistry, Institute of Chemistry, Faculty of Sciences, Pavol Jozef Šafárik University, 04001 Košice, SlovakiaDepartment of Biochemistry, Institute of Chemistry, Faculty of Sciences, Pavol Jozef Šafárik University, 04001 Košice, SlovakiaDepartment of Biochemistry, Institute of Chemistry, Faculty of Sciences, Pavol Jozef Šafárik University, 04001 Košice, SlovakiaThe involvement of G-quadruplex (G4) structures in nucleic acids in various molecular processes in cells such as replication, gene-pausing, the expression of crucial cancer-related genes and DNA damage repair is well known. The compounds targeting G4 usually bind directly to the G4 structure, but some ligands can also facilitate the G4 folding of unfolded G-rich sequences and stabilize them even without the presence of monovalent ions such as sodium or potassium. Interestingly, some G4-ligand complexes can show a clear induced CD signal, a feature which is indirect proof of the ligand interaction. Based on the dichroic spectral profile it is not only possible to confirm the presence of a G4 structure but also to determine its topology. In this study we examine the potential of the commercially available Rhodamine 6G (RhG) as a G4 ligand. RhG tends to convert antiparallel G4 structures to parallel forms in a manner similar to that of Thiazole Orange. Our results confirm the very high selectivity of this ligand to the G4 structure. Moreover, the parallel topology of G4 can be verified unambiguously based on the specific induced CD profile of the G4-RhG complex. This feature has been verified on more than 50 different DNA sequences forming various non-canonical structural motifs.https://www.mdpi.com/1422-0067/22/14/7639G-quadruplexligandrhodaminethiazole orangethioflavin T
spellingShingle Lukáš Trizna
Ladislav Janovec
Andrea Halaganová
Viktor Víglaský
Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
International Journal of Molecular Sciences
G-quadruplex
ligand
rhodamine
thiazole orange
thioflavin T
title Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
title_full Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
title_fullStr Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
title_full_unstemmed Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
title_short Rhodamine 6G-Ligand Influencing G-Quadruplex Stability and Topology
title_sort rhodamine 6g ligand influencing g quadruplex stability and topology
topic G-quadruplex
ligand
rhodamine
thiazole orange
thioflavin T
url https://www.mdpi.com/1422-0067/22/14/7639
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AT ladislavjanovec rhodamine6gligandinfluencinggquadruplexstabilityandtopology
AT andreahalaganova rhodamine6gligandinfluencinggquadruplexstabilityandtopology
AT viktorviglasky rhodamine6gligandinfluencinggquadruplexstabilityandtopology