Tuning G-Quadruplex Nanostructures with Lipids. Towards Designing Hybrid Scaffolds for Oligonucleotide Delivery.
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.
['Grijalvo|Santiago|S|0000-0002-8405-4844', 'Clua|Anna|A|', 'Eres|Marc|M|', 'Gargallo|Raimundo|R|0000-0001-8716-8356', 'Eritja|Ramon|R|0000-0001-5383-9334']
D000818:Animals D001703:Biophysics D045744:Cell Line, Tumor D002942:Circular Dichroism D054856:G-Quadruplexes D057809:HEK293 Cells D006367:HeLa Cells D006801:Humans D008055:Lipids D008156:Luciferases D008856:Microscopy, Fluorescence D049329:Nanostructures D009690:Nucleic Acid Conformation D009841:Oligonucleotides D016376:Oligonucleotides, Antisense D048790:Renilla D014162:Transfection
G-quadruplex lipids solid-phase antisense oligonucleotides luciferase circular dichroism gene delivery gene transfection nucleic acid conjugates solution-phase