Telomerase inhibitors--oligonucleotide phosphoramidates as potential therapeutic agents.
We have designed, synthesized, and evaluated using physical, chemical and biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, and 2'-arabino-fluoro oligonucleotide phosphoramidates, as well as novel N3'-->P5' thio-phosphoramidates. The compounds demonstrated sequence specific and dose dependent activity with IC50 values in the sub-nM to pM concentration range.
Gryaznov
S
S
Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA.
Pongracz
K
K
Matray
T
T
Schultz
R
R
Pruzan
R
R
Aimi
J
J
Chin
A
A
Harley
C
C
Shea-Herbert
B
B
Shay
J
J
Oshima
Y
Y
Asai
A
A
Yamashita
Y
Y
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010756:Phosphoric Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors*
D000577:Amides; D004791:Enzyme Inhibitors; D009841:Oligonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D019098:Telomerase