Next Article in Journal
Structural, Thermal and Mechanical Assessment of Green Compounds with Natural Rubber
Previous Article in Journal
Surface Microfabrication of Lactic Acid–Glycolic Acid Copolymers Using a Gas-Permeable Porous Mold
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Macromol
Volume 4
Issue 3
10.3390/macromol4030033
macromol-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

G-Quadruplex DNA as a Macromolecular Target for Semi-Synthetic Isoflavones Bearing B-Ring Tosylation

by
Giovanni Ribaudo
1,
Margrate Anyanwu
1,
Matteo Giannangeli
1,
Erika Oselladore
1,
Alberto Ongaro
2,
Maurizio Memo
1 and
Alessandra Gianoncelli
1,*
1
Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
2
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via Marzolo 5, 35131 Padova, Italy
*
Author to whom correspondence should be addressed.
Macromol 2024, 4(3), 556-565; https://doi.org/10.3390/macromol4030033
Submission received: 27 June 2024 / Revised: 29 July 2024 / Accepted: 3 August 2024 / Published: 7 August 2024
Browse Figures
Versions Notes

Abstract

Guanine-rich sequences of nucleic acids, including DNA and RNA, are known to fold into non-canonical structures named G-quadruplexes (G4s). Such arrangements of these macromolecular polymers are mainly located in telomeres and in promoter regions of oncogenes and, for this reason, they represent a potential target for compounds with therapeutic applications. In fact, the ligand-mediated stabilization of G4s inhibits telomerase and the activity of transcriptional machinery and counteracts cancer cell immortalization. Flavonoids, along with other classes of small molecules, have been previously tested for their ability to stabilize G4s, but the mechanism of their interaction has not been fully elucidated. In the current work, we report a multi-technique investigation on the binding of tosylated isoflavones obtained by the B-ring modification of compounds from Maclura pomifera to a telomeric DNA sequence. Our study demonstrates that such derivatization leads to compounds showing lower binding affinity but with an increased selectivity toward G4 with respect to double-stranded DNA. The binding mode to the macromolecular target G4 was studied by combining results from electrospray mass spectrometry binding studies, nuclear magnetic resonance experiments and computational simulations. Overall, our findings show that tosylation influences the selectivity toward the macromolecular target by affecting the interaction mode with the nucleic acid.
Keywords: DNA; G-quadruplex; flavonoids; ESI-MS; molecular modeling; molecular dynamics; drug discovery DNA; G-quadruplex; flavonoids; ESI-MS; molecular modeling; molecular dynamics; drug discovery

Share and Cite

MDPI and ACS Style

Ribaudo, G.; Anyanwu, M.; Giannangeli, M.; Oselladore, E.; Ongaro, A.; Memo, M.; Gianoncelli, A. G-Quadruplex DNA as a Macromolecular Target for Semi-Synthetic Isoflavones Bearing B-Ring Tosylation. Macromol 2024, 4, 556-565. https://doi.org/10.3390/macromol4030033

AMA Style

Ribaudo G, Anyanwu M, Giannangeli M, Oselladore E, Ongaro A, Memo M, Gianoncelli A. G-Quadruplex DNA as a Macromolecular Target for Semi-Synthetic Isoflavones Bearing B-Ring Tosylation. Macromol. 2024; 4(3):556-565. https://doi.org/10.3390/macromol4030033

Chicago/Turabian Style

Ribaudo, Giovanni, Margrate Anyanwu, Matteo Giannangeli, Erika Oselladore, Alberto Ongaro, Maurizio Memo, and Alessandra Gianoncelli. 2024. "G-Quadruplex DNA as a Macromolecular Target for Semi-Synthetic Isoflavones Bearing B-Ring Tosylation" Macromol 4, no. 3: 556-565. https://doi.org/10.3390/macromol4030033

APA Style

Ribaudo, G., Anyanwu, M., Giannangeli, M., Oselladore, E., Ongaro, A., Memo, M., & Gianoncelli, A. (2024). G-Quadruplex DNA as a Macromolecular Target for Semi-Synthetic Isoflavones Bearing B-Ring Tosylation. Macromol, 4(3), 556-565. https://doi.org/10.3390/macromol4030033

Article Metrics

Back to TopTop