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Int J Mol Sci ; 22(1)2020 Dec 24.
Artículo en Inglés | MEDLINE | ID: mdl-33374392

RESUMEN

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.


Asunto(s)
G-Cuádruplex , Lípidos/química , Nanoestructuras/química , Oligonucleótidos/genética , Animales , Biofisica , Línea Celular Tumoral , Dicroismo Circular , Células HEK293 , Células HeLa , Humanos , Luciferasas/metabolismo , Microscopía Fluorescente , Conformación de Ácido Nucleico , Oligonucleótidos/química , Oligonucleótidos Antisentido , Renilla/enzimología , Transfección
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