Telomere shortening in human HL60 cells by treatment with 3'-azido-2',3'-dideoxynucleosides and telomerase inhibition by their 5'-triphosphates.
Telomerase is thought to play an important role in the mechanism of tumor cell immortalization by maintenance of telomere length. To obtain information on the susceptibility of telomerase to nucleoside analogues, the effects of base-modified 3'-azido-2',3'-dideoxynucleoside triphosphates on the enzyme were investigated. It is suggested that the 2-amino group of the nucleotide purine nucleus is important for the inhibitory activity. Telomere shortening caused by long-term treatment with these nucleosides is also described.
Liu
Xiaohong
X
Biotechnology Research Center, Teikyo University of Science and Technology, Uenohara, Yamanashi, Japan.
Inomata
Motoko
M
Ogawara
Tsukasa
T
Saneyoshi
Mineo
M
Yamaguchi
Toyofumi
T
D016048:Dideoxyadenosine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000187:drug effects*
D015224:Dideoxynucleosides; D054306:Dideoxynucleotides; D004791:Enzyme Inhibitors; C055319:3'-azido-2,6-diaminopurine-2',3'-dideoxyriboside; D016048:Dideoxyadenosine; D019098:Telomerase