Telomerase-inhibitory effects of the triphosphate derivatives of some biologically active nucleosides.
Telomerase is a ribonucleoprotein reverse transcriptase that uses its internal RNA moiety as a template for synthesis of telomere repeats. To clarify the susceptibility of telomerase to HIV-1 reverse transcriptase inhibitors (RT), we investigated the inhibitory effects of 3'-azido-3'-deoxythymidine 5'-triphosphate (AZTTP), which is known to be a potent HIV-1 RT inhibitor, and acyclovir triphosphate (ACVTP). Lineweaver-Burk plot analyses showed that the inhibition mode of these compounds was competitive with the substrate dNTP counterpart. However, inhibition by AZTTP was weak (Ki = 15 microM, Km of dTTP = 7.1 microM). Interestingly, ACVTP showed considerable inhibition. The Ki value of ACVTP was 5.0 microM, being smaller than the Km of dGTP (12 microM).
Yamaguchi
T
T
Department of Biological Sciences, Biotechnology Research Center, Teikyo University of Science and Technology, Uenohara, Yamanashi 409-0193, Japan.
Takayama
Y
Y
Saito
M
M
Ishikawa
F
F
Saneyoshi
M
M
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides; D006367:HeLa Cells; D006801:Humans; D009705:Nucleosides / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019098:Telomerase / Q000378:metabolism*; D013942:Thymine Nucleotides / Q000737:chemistry / Q000494:pharmacology*; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
D054306:Dideoxynucleotides; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D013942:Thymine Nucleotides; D015215:Zidovudine; C025114:acyclovir triphosphate; C052873:zidovudine triphosphate; D019098:Telomerase; D000212:Acyclovir