Synthetic Nucleosides and Nucleotides. 43. Inhibition of Vertebrate Telomerases by Carbocyclic Oxetanocin G (C.OXT-G) Triphosphate Analogues and Influence of C.OXT-G Treatment on Telomere Length in Human HL60 Cells

Telomerase, responsible for telomere synthesis, is expressed in ∼ 90% of human tumor cells but seldom in normal somatic cells. In this study, inhibition by carbocyclic oxetanocin G triphosphate (C.OXT-GTP) and its analogues was investigated in order to clarify the susceptibility of telomerase to various nucleotide analogues. C.OXT-GTP competitively inhibited telomerase activity with respect to dGTP. However, C.OXT-GTP had a potent inhibitory effect on DNA polymerase α. It was examined whether the nucleoside (C.OXT-G) was able to alter telomere length in cultured human HL60 cells. Contrary to expectation, long-term treatment with 10 μM C.OXT-G was found to cause telomere lengthening.