Directing quadruplex-stabilizing drugs to the telomere: synthesis and properties of acridine-oligonucleotide conjugates.
Conjugates containing quadruplex-stabilizing acridines linked to oligonucleotides that are complementary to the G-rich human telomere sequence were synthesized. Acylation of 3,6-diaminoacridine followed by two Michael reactions provided derivatives suitable for conjugation, which were coupled to resin-linked amine-modified oligonucleotides by activating the carboxyl group with pentafluorophenyl 4-nitrobenzenesulfonate. After deprotection with aqueous ammonia at room temperature, conjugates incorporating different acridines, linkers, and oligonucleotide sequences were obtained. These were tested for their ability to stabilize intramolecular DNA quadruplexes that are based on the human telomeric repeat sequence (GGGTTA)(n).
Casals
Joan
J
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
Debéthune
Laurent
L
Alvarez
Karine
K
Risitano
Antonina
A
Fox
Keith R
KR
Grandas
Anna
A
Pedroso
Enrique
E
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D000166:Acridines; D009841:Oligonucleotides