Effect and mechanism of beta-L-D4A on DNA polymerase alpha

World J Gastroenterol. 2007 Dec 14;13(46):6243-8. doi: 10.3748/wjg.v13.i46.6243.

Abstract

Aim: To investigate the safety of beta-L-D4A on DNA polymerase alpha.

Methods: Ion exchange chromatography was used to separate DNA polymerase alpha from crude extract of human Hela cells. Detailed kinetic parameters were determined for beta-L-D4A against DNA polymerase alpha.

Results: DNA polymerase alpha was purified with 4% yield and 31000 units/mg specific activity. The Michaelis constant (Km = 3.22 micromol/L), 50% inhibition concentration (IC50 = 178.49 micromol/L) and inhibition constant (Ki = 126 micromol/L) of beta-L-D4A were determined by kinetic analysis.

Conclusion: beta-L-D4A is a more safe nucleoside for hepatitis B virus infection with a lower host toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, DEAE-Cellulose
  • Chromatography, Ion Exchange
  • DNA Polymerase I / drug effects*
  • Dideoxyadenosine / adverse effects
  • Dideoxyadenosine / analogs & derivatives*
  • Dideoxyadenosine / pharmacology
  • Dideoxyadenosine / therapeutic use
  • Enzyme Activation / drug effects
  • Female
  • HeLa Cells
  • Hepatitis B / drug therapy
  • Hepatitis B virus / physiology
  • Humans
  • Nucleosides / adverse effects
  • Nucleosides / pharmacology*
  • Nucleosides / therapeutic use
  • Virus Replication / drug effects

Substances

  • Nucleosides
  • Dideoxyadenosine
  • 2'3'-didehydro-2'3'-dideoxyadenosine
  • DNA Polymerase I