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Article

G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides

Department of Nucleic Acids Bioengineering, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12/14, 61-704 Poznan, Poland
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Academic Editors: Aldo Galeone, Veronica Esposito and Antonella Virgilio
Int. J. Mol. Sci. 2021, 22(9), 4941; https://doi.org/10.3390/ijms22094941
Received: 8 April 2021 / Revised: 3 May 2021 / Accepted: 4 May 2021 / Published: 6 May 2021
G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties. View Full-Text
Keywords: G-quadruplex; UV melting; circular dichroism; antiproliferative activity; anticancer agents G-quadruplex; UV melting; circular dichroism; antiproliferative activity; anticancer agents
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MDPI and ACS Style

Roxo, C.; Kotkowiak, W.; Pasternak, A. G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides. Int. J. Mol. Sci. 2021, 22, 4941. https://doi.org/10.3390/ijms22094941

AMA Style

Roxo C, Kotkowiak W, Pasternak A. G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides. International Journal of Molecular Sciences. 2021; 22(9):4941. https://doi.org/10.3390/ijms22094941

Chicago/Turabian Style

Roxo, Carolina, Weronika Kotkowiak, and Anna Pasternak. 2021. "G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides" International Journal of Molecular Sciences 22, no. 9: 4941. https://doi.org/10.3390/ijms22094941

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