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

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.