First enzymatic galactosylation of acyclic nucleoside drugs by ¥�-galactosidase: Synthesis of water-soluble ¥�-D-galactosidic prodrugs
2014
Yan, L.Q., South China University of Technology, Guangzhou, China | Li, N., South China University of Technology, Guangzhou, China | Zong, M.H., South China University of Technology, Guangzhou, China
Acyclic nucleoside analogs constitute an important group of antiviral agents. However, these nucleoside drugs suffer from poor water solubility and low oral bioavailability in the clinic use. In the present work, the enzymatic synthesis of the water-soluble galactosidic prodrugs of acyclic nucleosides by using bovine liver ¥�-galactosidase was described. In the enzymatic transgalactosylation between acyclovir (ACV) and o-nitrophenyl ¥�-galactopyranoside (oNPGal), the optimum enzyme dosage, buffer pH, temperature and molar ratio of ACV to oNPGal were 0.225 U/mL, 7.0, 40¡�C and 2.5, respectively, under which the initial reaction rate and the yield reached 0.40 mM/h and 29%, respectively. In addition, this enzyme could accept ganciclovir (GCV) and penciclovir (PCV) as substrates, affording the corresponding 4¡¯-¥�-galactosylated derivatives with the yields of 26% and 71%, respectively.
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