Inhibition of human telomerase by nucleotide analogues bearing a hydrophobic group.
Telomerase, which synthesizes telomeric DNA in eukaryotic cells, is classified as a reverse transcriptase. To clarify the susceptibility of telomerase to nucleoside 5'-triphosphates bearing a hydrophobic group on the base moiety, we studied the inhibitory effects of 2',3'-dideoxy-5-styryluridine 5'-triphosphate analogues and 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)purine 5'-triphosphate analogues on telomerase activity using a quantitative 'stretch PCR' assay. 2',3'-Dideoxy-5-styryluridine 5'-triphosphate (StddUTP) showed more potent inhibition than 2',3'-dideoxythymidine 5'-triphosphate (ddTTP). On the other hand, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylphenyl)guanine 5'-triphosphate (BuParaGTP) showed no inhibition, even though 9-(beta-D-arabinofuranosyl)guanine 5'-triphosphate (araGTP) is a potent inhibitor of telomerase. The influence on telomerase of hydrophobic substituents on the base moieties of nucleotides is described.
Yamaguchi
T
T
Department of Biological Sciences, Biotechnology Research Center, Teikyo University of Science and Technology, Uenohara, Yamanashi 409-0193, Japan.
Kawarai
M
M
Takeshita
Y
Y
Ishikawa
F
F
Saneyoshi
M
M
D001088:Arabinonucleotides / Q000737:chemistry / Q000494:pharmacology; D054306:Dideoxynucleotides; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*; D013942:Thymine Nucleotides / Q000737:chemistry / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology
D001088:Arabinonucleotides; D054306:Dideoxynucleotides; D004791:Enzyme Inhibitors; D009705:Nucleosides; D013942:Thymine Nucleotides; C022206:9-beta-D-arabinofuranosylguanosine 5'-triphosphate; D006160:Guanosine Triphosphate; D019098:Telomerase; C017216:2',3'-dideoxythymidine triphosphate; D014544:Uridine Triphosphate