Thymidine Phosphorylase – Based Enzymatic Synthesis of Modified Nucleosides
Data
2016Autorius
Tauraitė, Daiva
Šiškovaitė, Greta
Meškys, Rolandas
Urbonavičius, Jaunius
Metaduomenys
Rodyti detalų aprašąSantrauka
Modified nucleosides or nucleotides can inhibit various enzymes, and can act both as anticancer or antiviral agents. The chemical synthesis of 5-carboxyuridine esters is complicated. To overcome this, we performed a one-pot reaction using Escherichia coli thymidine phosphorylase (EC 2.4.2.4), which was active towards various 5-carboxyuracil derivatives as well as 5-fluorouracil, for the production of functionalized unnatural uridine nucleosides. Thymidine phosphorylase mediates nucleobase-exchange reaction to convert thymidine or uridine to modified nucleosides possessing a functional group at the 5th position. It was shown that the methyl, ethyl, propyl, isopropyl, butyl, cyclohexyl, cyclooctyl, and prop-2-ynyl esters of 5-carboxyuracil and 5-fluorouracil are substrates of thymidine phosphorylase, thus allowing enzymatic synthesis of modified nucleosides. This research was supported by the Research Council of Lithuania (LMT) grant [SEN-07/2015].