Tenofovir diphosphate is a poor substrate and a weak inhibitor of rat DNA polymerases alpha, delta, and epsilon*

Antimicrob Agents Chemother. 2002 May;46(5):1610-3. doi: 10.1128/AAC.46.5.1610-1613.2002.

Abstract

Tenofovir diphosphate (PMPApp) is a weak inhibitor of DNA polymerases (pol) alpha, delta, and epsilon*, with values for the Ki for PMPApp ((PMPApp)Ki) relative to the Km for dATP ((dATP)Km) of 10.2, 10.2, and 15.2, respectively. Its incorporation into DNA was about 1,000-fold less efficient than that of dATP, with (PMPApp)Km values 350-, 2,155-, and 187-fold higher than (dATP)Km values for pol alpha, delta, and epsilon*, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / metabolism*
  • Adenine / pharmacology
  • Animals
  • Anti-HIV Agents / metabolism*
  • Anti-HIV Agents / pharmacology
  • DNA Polymerase I / antagonists & inhibitors
  • DNA Polymerase I / metabolism
  • DNA Polymerase II / antagonists & inhibitors
  • DNA Polymerase II / metabolism
  • DNA Polymerase III / antagonists & inhibitors
  • DNA Polymerase III / metabolism
  • DNA-Directed DNA Polymerase / metabolism*
  • Nucleic Acid Synthesis Inhibitors*
  • Organophosphonates*
  • Organophosphorus Compounds / metabolism*
  • Organophosphorus Compounds / pharmacology
  • Rats
  • Reverse Transcriptase Inhibitors / metabolism*
  • Reverse Transcriptase Inhibitors / pharmacology
  • Tenofovir

Substances

  • Anti-HIV Agents
  • Nucleic Acid Synthesis Inhibitors
  • Organophosphonates
  • Organophosphorus Compounds
  • Reverse Transcriptase Inhibitors
  • Tenofovir
  • DNA Polymerase I
  • DNA Polymerase II
  • DNA Polymerase III
  • DNA-Directed DNA Polymerase
  • Adenine