Synthetic nucleosides and nucleotides. 40. Selective inhibition of eukaryotic DNA polymerase alpha by 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino) adenine 5'-triphosphate (BuAaraATP) and its 2'-up azido analog: synthesis and enzymatic evaluations.
Starting from 2',3',5'-tri-O-acetyl-2-iodoadenosine, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine and its 2'(S)-azido counterparts were synthesized in seven steps. These exhibited only moderate growth-inhibitory effects against mouse leukemic P388 cells (IC50 = 13-24 microM), although 5'-triphosphate derivatives showed strong and selective inhibitory action on calf thymus DNA polymerase alpha, but not on beta- and epsilon-polymerases from eukaryotes.
Department of Biological Sciences, Teikyo University of Science and Technology, Yamanashi, Japan.
A
A
Tomikawa
M
M
Seno
K
K
Sato-Kiyotaki
C
C
Ohtsuki
T
T
Hirai
T
T
Yamaguchi
T
T
Kawaguchi
S
S
Yoshida
M
M
Saneyoshi
D000225:Adenine / Q000031:analogs & derivatives; D000241:Adenosine / Q000031:analogs & derivatives; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives*; D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis*; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides / Q000138:chemical synthesis*; D009711:Nucleotides / Q000138:chemical synthesis*; D014407:Tumor Cells, Cultured
D001391:Azo Compounds; D004791:Enzyme Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides; D009711:Nucleotides; D000255:Adenosine Triphosphate; D000225:Adenine; D000241:Adenosine