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 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 IC50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC50 values 100-1000-fold higher.
Pongracz
Krisztina
K
Geron Corporation, Menlo Park, California 94025, USA. kpongracz@geron.com
Li
Shihong
S
Herbert
Brittney-Shea
BS
Pruzan
Ronald
R
Wunder
Ellen
E
Chin
Allison
A
Piatyszek
Mieczyslaw
M
Shay
Jerry
J
Gryaznov
Sergei M
SM
D000577:Amides; D001483:Base Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D010756:Phosphoric Acids; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*
D000577:Amides; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009838:Oligodeoxyribonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D019098:Telomerase