Nucleoside Phosphorylases

E.S.LEWKOWICZ, A.M. IRIBARREN

CURRENT ORGANIC CHEMISTRY

Bentham Science Publishers Ltd

Año: 2006 vol. 10 p. 1197 - 1215

1385-2728

Nucleoside phosphorylases (NPs) are enzymes involved in the salvage pathways of nucleosides and therefore are important targets for the development of antitumor therapies. Structural studies revealed that there are two families of NPs that catalyse the phosphorolysis of all nucleosides. Differences in specificity between NPs from different sources have been observed and reviewed. In the presence of inorganic orthophosphate, the phosphorolysis of the ribo- and deoxyribonucleoside glycosidic bonds affords the corresponding base and ribose- or deoxyribose-1-phosphate, respectively. The reaction is reversible and in the case of purine phosphorylases, the thermodynamic equilibrium is shifted towards nucleoside synthesis. Therefore, the action of these enzymes makes a possible a transglycosylation reaction in a two step process. Many NPs, mainly bacterial ones, have been explored as tools for the chemoenzymatic synthesis of nucleosides as a competitive alternative to chemical synthesis. This route not only provides a convenient solution to the stereo- and regioselective requirements but also offers environmentally clean technologies using mild reaction conditions. Owing to the multienzymatic nature of this biotransformation, which involves intracellular enzymes, the use of whole cells appears as an adequate procedure that avoids expensive and laborious purification steps. This methodology is of particular interest due to the important applications of nucleoside analogues. These molecules are extensively used as antiviral and anticancer agents because of their ability to act as reverse transcriptase inhibitors or chain terminators in RNA or DNA synthesis. This chapter intends to summarise recent advances in the preparation of pharmacological active nucleosides using free or immobilised isolated enzymes or resting cells, focusing on the synthetic potential of NPs.