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Telomerase inhibitors--oligonucleotide phosphoramidates as potential therapeutic agents
S Gryaznov1, K Pongracz, T Matray
1Geron Corporation, 230 Constitution Drive, Menlo Park, California 94025, USA.
Abstract:
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.
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