Modulating the G-Quadruplex and Duplex DNA Binding by Controlling the Charge of Fluorescent Molecules

Overview

Journal Chemistry

Specialty Chemistry

Date 2022 Nov 1

PMID 36318180

Authors

Ariadna Gil-Martinez

Sonia Lopez-Molina

Cristina Galiana-Rosello

Andrea Lazaro-Gomez

Friederike Schluter

Fabio Rizzo

Jorge Gonzalez-Garcia

Affiliations

Soon will be listed here.

Abstract

Two fluorescent and non-toxic spirobifluorene molecules bearing either positive (Spiro-NMe3) or negative (Spiro-SO3) charged moieties attached to the same aromatic structure have been investigated as binders for DNA. The novel Spiro-NMe3 containing four alkylammonium substituents interacts with G-quadruplex (G4) DNA structures and shows preference for G4s over duplex by means of FRET melting and fluorescence experiments. The interaction is governed by the charged substituents of the ligands as deduced from the lower binding of the sulfonate analogue (Spiro-SO3). On the contrary, Spiro-SO3 exhibits higher binding affinity to duplex DNA structure than to G4. Both molecules show a moderate quenching of the fluorescence upon DNA binding. The confocal microscopy evaluation shows the internalization of both molecules in HeLa cells and their lysosomal accumulation.

Citing Articles

Modulating the G-Quadruplex and Duplex DNA Binding by Controlling the Charge of Fluorescent Molecules.

Gil-Martinez A, Lopez-Molina S, Galiana-Rosello C, Lazaro-Gomez A, Schluter F, Rizzo F Chemistry. 2022; 29(6):e202203094.

PMID: 36318180 PMC: 10107164. DOI: 10.1002/chem.202203094.

References

Liu L, Liu W, Wang K, Zhu B, Xia X, Ji L . Quantitative Detection of G-Quadruplex DNA in Live Cells Based on Photon Counts and Complex Structure Discrimination. Angew Chem Int Ed Engl. 2020; 59(24):9719-9726. DOI: 10.1002/anie.202002422. View

Zuffo M, Guedin A, Leriche E, Doria F, Pirota V, Gabelica V . More is not always better: finding the right trade-off between affinity and selectivity of a G-quadruplex ligand. Nucleic Acids Res. 2018; 46(19):e115. PMC: 6212845. DOI: 10.1093/nar/gky607. View

Palma E, Carvalho J, Cruz C, Paulo A . Metal-Based G-Quadruplex Binders for Cancer Theranostics. Pharmaceuticals (Basel). 2021; 14(7). PMC: 8308583. DOI: 10.3390/ph14070605. View

Chambers V, Marsico G, Boutell J, Di Antonio M, Smith G, Balasubramanian S . High-throughput sequencing of DNA G-quadruplex structures in the human genome. Nat Biotechnol. 2015; 33(8):877-81. DOI: 10.1038/nbt.3295. View

Laguerre A, Stefan L, Larrouy M, Genest D, Novotna J, Pirrotta M . A twice-as-smart synthetic G-quartet: PyroTASQ is both a smart quadruplex ligand and a smart fluorescent probe. J Am Chem Soc. 2014; 136(35):12406-14. DOI: 10.1021/ja506331x. View

Polo F, Rizzo F, Veiga-Gutierrez M, De Cola L, Quici S . Efficient greenish blue electrochemiluminescence from fluorene and spirobifluorene derivatives. J Am Chem Soc. 2012; 134(37):15402-9. DOI: 10.1021/ja3054018. View

Shivalingam A, Izquierdo M, Le Marois A, Vysniauskas A, Suhling K, Kuimova M . The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy. Nat Commun. 2015; 6:8178. PMC: 4579598. DOI: 10.1038/ncomms9178. View

Grande V, Doria F, Freccero M, Wurthner F . An Aggregating Amphiphilic Squaraine: A Light-up Probe That Discriminates Parallel G-Quadruplexes. Angew Chem Int Ed Engl. 2017; 56(26):7520-7524. DOI: 10.1002/anie.201702096. View

Vummidi B, Alzeer J, Luedtke N . Fluorescent probes for G-quadruplex structures. Chembiochem. 2013; 14(5):540-58. DOI: 10.1002/cbic.201200612. View

10.

Schluter F, Riehemann K, Kehr N, Quici S, Daniliuc C, Rizzo F . A highly fluorescent water soluble spirobifluorene dye with a large Stokes shift: synthesis, characterization and bio-applications. Chem Commun (Camb). 2018; 54(6):642-645. DOI: 10.1039/c7cc08761f. View

11.

Neidle S . Quadruplex Nucleic Acids as Novel Therapeutic Targets. J Med Chem. 2016; 59(13):5987-6011. DOI: 10.1021/acs.jmedchem.5b01835. View

12.

Haddach M, Schwaebe M, Michaux J, Nagasawa J, OBrien S, Whitten J . Discovery of CX-5461, the First Direct and Selective Inhibitor of RNA Polymerase I, for Cancer Therapeutics. ACS Med Chem Lett. 2014; 3(7):602-6. PMC: 4025669. DOI: 10.1021/ml300110s. View

13.

Collie G, Promontorio R, Hampel S, Micco M, Neidle S, Parkinson G . Structural basis for telomeric G-quadruplex targeting by naphthalene diimide ligands. J Am Chem Soc. 2012; 134(5):2723-31. DOI: 10.1021/ja2102423. View

14.

DOria F, Nadai M, Zuffo M, Perrone R, Freccero M, Richter S . A red-NIR fluorescent dye detecting nuclear DNA G-quadruplexes: in vitro analysis and cell imaging. Chem Commun (Camb). 2017; 53(14):2268-2271. PMC: 5471928. DOI: 10.1039/c6cc08492c. View

15.

Saragi T, Spehr T, Siebert A, Fuhrmann-Lieker T, Salbeck J . Spiro compounds for organic optoelectronics. Chem Rev. 2007; 107(4):1011-65. DOI: 10.1021/cr0501341. View

16.

Yan J, Chen S, Liu H, Ye W, Ou T, Tan J . Development of a new colorimetric and red-emitting fluorescent dual probe for G-quadruplex nucleic acids. Chem Commun (Camb). 2014; 50(52):6927-30. DOI: 10.1039/c4cc01472c. View

17.

Gil-Martinez A, Lopez-Molina S, Galiana-Rosello C, Lazaro-Gomez A, Schluter F, Rizzo F . Modulating the G-Quadruplex and Duplex DNA Binding by Controlling the Charge of Fluorescent Molecules. Chemistry. 2022; 29(6):e202203094. PMC: 10107164. DOI: 10.1002/chem.202203094. View

18.

Ma D, Zhang Z, Wang M, Lu L, Zhong H, Leung C . Recent Developments in G-Quadruplex Probes. Chem Biol. 2015; 22(7):812-28. DOI: 10.1016/j.chembiol.2015.06.016. View

19.

Spiegel J, Adhikari S, Balasubramanian S . The Structure and Function of DNA G-Quadruplexes. Trends Chem. 2020; 2(2):123-136. PMC: 7472594. DOI: 10.1016/j.trechm.2019.07.002. View

20.

Raguseo F, Chowdhury S, Minard A, Di Antonio M . Chemical-biology approaches to probe DNA and RNA G-quadruplex structures in the genome. Chem Commun (Camb). 2020; 56(9):1317-1324. DOI: 10.1039/c9cc09107f. View