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©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2007; 13(46): 6243-6248
Published online Dec 14, 2007. doi: 10.3748/wjg.v13.i46.6243
Published online Dec 14, 2007. doi: 10.3748/wjg.v13.i46.6243
Effect and mechanism of β-L-D4A on DNA polymerase α
Yan Li, Ju-Sheng Lin, Ying-Hui Zhang, Xiao-Yan Wang, Ying Chang, Xing-Xing He, Institute of Liver Diseases, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Street, Wuhan 430030, Hubei Province, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No. 30330680
Correspondence to: Dr. Ju-Sheng Lin, Professor, Institute of Liver Diseases, Tongji Medical College, 1095 Jiefang Street, Wuhan 430030, Hubei Province, China. jslin@tjh.tjmu.edu.cn
Telephone: + 86-27-83663661 Fax: +86-27-83663661
Received: July 28, 2007
Revised: August 27, 2007
Accepted: September 20, 2007
Published online: December 14, 2007
Revised: August 27, 2007
Accepted: September 20, 2007
Published online: December 14, 2007
Abstract
AIM: To investigate the safety of β-L-D4A on DNA polymerase α.
METHODS: Ion exchange chromatography was used to separate DNA polymerase α from crude extract of human Hela cells. Detailed kinetic parameters were determined for β-L-D4A against DNA polymerase α.
RESULTS: DNA polymerase α was purified with 4% yield and 31 000 units/mg specific activity. The Michaelis constant (Km = 3.22 μmol/L), 50% inhibition concentration (IC50 = 178.49 μmol/L) and inhibition constant (Ki = 126 μmol/L) of β-L-D4A were determined by kinetic analysis.
CONCLUSION: β-L-D4A is a more safe nucleoside for hepatitis B virus (HBV) infection with a lower host toxicity.
Keywords: Nucleoside, β-L-D4A, DNA polymerase α, Kinetic study, Side effect, Hepatitis B virus