TELOMERASE INHIBITORS – OLIGONUCLEOTIDE PHOSPHORAMIDATES AS POTENTIAL THERAPEUTIC AGENTS

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.