Novel Short Oligonucleotide Conjugates as Inhibitors of Human Telomerase

A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of...

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Bibliographic Details
Published in:Nucleosides, nucleotides & nucleic acids nucleotides & nucleic acids, 2003-10, Vol.22 (5-8), p.1627-1629
Main Authors: Pongracz, Krisztina, Li, Shihong, Herbert, Brittney-Shea, Pruzan, Ronald, Wunder, Ellen, Chin, Allison, Piatyszek, Mieczyslaw, Shay, Jerry, Gryaznov, Sergei M.
Format: Article
Language:English
Subjects:
Amides
Base Sequence
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
Fluorescent Dyes
Humans
Oligodeoxyribonucleotides - chemical synthesis
Oligodeoxyribonucleotides - pharmacology
Oligonucleotide thio-phosphoramidates
Phosphoric Acids
Structure-Activity Relationship
Telomerase - antagonists & inhibitors
Telomerase inhibitors
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Summary:A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3′ → P5′ phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5′- or preferably to the 3′- termini. The most potent compounds in the series inhibited telomerase with low nM IC 50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC 50 values 100-1000-fold higher.
ISSN:1525-7770
1532-2335
DOI:10.1081/NCN-120023085