title: Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homo-oligonucleotide.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4012 Debrecen, Hungary.
authors.forename: Ilona
authors.initials: I
authors.lastname: Tarkanyi
authors.forename: András
authors.initials: A
authors.lastname: Horváth
authors.forename: Istvan
authors.initials: I
authors.lastname: Szatmari
authors.forename: Helga
authors.initials: H
authors.lastname: Eizert
authors.forename: György
authors.initials: G
authors.lastname: Vámosi
authors.forename: Sándor
authors.initials: S
authors.lastname: Damjanovich
authors.forename: Evelyne
authors.initials: E
authors.lastname: Ségal-Bendirdjian
authors.forename: Janos
authors.initials: J
authors.lastname: Aradi
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D016376:Oligonucleotides, Antisense; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase