Design and characterization of N2-arylaminopurines which selectively inhibit replicative DNA synthesis and replication-specific DNA polymerases: guanine derivatives active on mammalian DNA polymerase alpha and bacterial DNA polymerase III

Nucleic Acids Res. 1982 Jul 24;10(14):4431-40. doi: 10.1093/nar/10.14.4431.


The 2-amino substituted derivatives of guanine, N2-(p-n-butylphenyl)guanine (BuPG) and N2-(3',4'-trimethylenephenyl) guanine (TMPG), were synthesized and found to selectively inhibit, respectively, HeLa cell DNA polymerase alpha (po1 alpha) and B. subtilis DNA polymerase III (po1 III). Both purines, like their corresponding uracil analogs, BuAu and TMAU (2,9), were specifically competitive with dGTP in their inhibitory action on their target polymerases. BuPG, the pol alpha-specific purine, was also toxic for HeLa cells in vivo, selectively inhibiting DNA synthesis. These N2-substituted purines, in contrast to the 6-substituted uracils, provide a structural basis for the synthesis of nucleosides and nucleotides with considerable potential as probes for the analysis of the structure of specific replicative DNA polymerases and their function in cellular DNA metabolism.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacillus subtilis / enzymology
  • Binding, Competitive
  • Cell Division / drug effects
  • DNA Polymerase II / antagonists & inhibitors*
  • DNA Polymerase III / antagonists & inhibitors*
  • DNA Replication / drug effects*
  • HeLa Cells / drug effects
  • HeLa Cells / enzymology
  • Humans
  • Kinetics
  • Nucleic Acid Synthesis Inhibitors*
  • Purines / chemical synthesis
  • Purines / pharmacology*
  • Structure-Activity Relationship


  • Nucleic Acid Synthesis Inhibitors
  • Purines
  • DNA Polymerase II
  • DNA Polymerase III