Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homo-oligonucleotide.
Most tumor cells attain their immortality by reactivating telomerase. We report here the telomerase inhibitory potential of chimeric oligonucleotides composed of a 13mer antisense sequence targeting the telomerase RNA template region and a (s4dU)n moiety at its 3' or 5'-end. The increase of the thiolated chain length enhances the telomerase inhibitory potential, but decreases specificity, indicated by HIV reverse transcriptase inhibition. Chimeras with 5' (s4dU)(n)s were more potent inhibitors than the antisense alone or the 3' modified ones. Cy5-labeled (s4dU)4AS and (s4dU)8AS proved the internalization of the oligonucleotides, raising the possibility to be tested as cellular anti-telomerase agents.
Tarkanyi
Ilona
I
Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
Horváth
András
A
Szatmari
Istvan
I
Eizert
Helga
H
Vámosi
György
G
Damjanovich
Sándor
S
Ségal-Bendirdjian
Evelyne
E
Aradi
Janos
J
D001483:Base Sequence; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006678:HIV / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013997:Time Factors
D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase