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Article

Tuning G-Quadruplex Nanostructures with Lipids. Towards Designing Hybrid Scaffolds for Oligonucleotide Delivery

1
Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, E-08034 Barcelona, Spain
2
Networking Center on Bioengineering, Biomaterials and Nanomedicine (CIBER BBN), Jordi Girona 18-26, E-08034 Barcelona, Spain
3
Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain
*
Author to whom correspondence should be addressed.
Dedicated to the memory of Dr. Enrique Pedroso Muller.
Int. J. Mol. Sci. 2021, 22(1), 121; https://doi.org/10.3390/ijms22010121
Received: 26 November 2020 / Revised: 15 December 2020 / Accepted: 21 December 2020 / Published: 24 December 2020
Two G-quadruplex forming oligonucleotides [d(TG4T)4 and d(TG6T)4] were selected as two tetramolecular quadruplex nanostructures because of their demonstrated ability to be modified with hydrophobic molecules. This allowed us to synthesize two series of G-quadruplex conjugates that differed in the number of G-tetrads, as well as in the terminal position of the lipid modification. Both solution and solid-phase syntheses were carried out to yield the corresponding lipid oligonucleotide conjugates modified at their 3′- and 5′-termini, respectively. Biophysical studies confirmed that the presence of saturated alkyl chains with different lengths did not affect the G-quadruplex integrity, but increased the stability. Next, the G-quadruplex domain was added to an 18-mer antisense oligonucleotide. Gene silencing studies confirmed the ability of such G-rich oligonucleotides to facilitate the inhibition of target Renilla luciferase without showing signs of toxicity in tumor cell lines. View Full-Text
Keywords: antisense oligonucleotides; circular dichroism; G-quadruplex; gene delivery; gene transfection; lipids; luciferase; nucleic acid conjugates; solid-phase; solution-phase antisense oligonucleotides; circular dichroism; G-quadruplex; gene delivery; gene transfection; lipids; luciferase; nucleic acid conjugates; solid-phase; solution-phase
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MDPI and ACS Style

Grijalvo, S.; Clua, A.; Eres, M.; Gargallo, R.; Eritja, R. Tuning G-Quadruplex Nanostructures with Lipids. Towards Designing Hybrid Scaffolds for Oligonucleotide Delivery. Int. J. Mol. Sci. 2021, 22, 121. https://doi.org/10.3390/ijms22010121

AMA Style

Grijalvo S, Clua A, Eres M, Gargallo R, Eritja R. Tuning G-Quadruplex Nanostructures with Lipids. Towards Designing Hybrid Scaffolds for Oligonucleotide Delivery. International Journal of Molecular Sciences. 2021; 22(1):121. https://doi.org/10.3390/ijms22010121

Chicago/Turabian Style

Grijalvo, Santiago; Clua, Anna; Eres, Marc; Gargallo, Raimundo; Eritja, Ramon. 2021. "Tuning G-Quadruplex Nanostructures with Lipids. Towards Designing Hybrid Scaffolds for Oligonucleotide Delivery" Int. J. Mol. Sci. 22, no. 1: 121. https://doi.org/10.3390/ijms22010121

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