Preparation of nucleosides, nucleotides and oligonucleotides

ELIZABETH LEWKOWICZ, LUIS IGLESIAS, JAVIER MONTSERRAT, MARIANA GALLO, JORGE TRELLES, ALEJANDRA ZINNI, ROSARIO MEDICI, MARISA TAVERNA-PORRO, RODRIGO PONTIGGIA AND ADOLFO IRIBARREN

Mombay

Simposio; Drug Discovery to Manufacturing: Global Partnering & New Science; 2004

IS3N

Nucleoside analogs are extensively used as antiviral and antitumor agents and therefore, much effort has been applied to the development of different chemical methods to synthesize these molecules. Among them biotransformations, which provide environmentally clean technologies and regio- and stereoselective processes, are becoming useful alternatives. The chemo-enzymatic preparation of modified nucleosides is being explored in our laboratory, using different approaches: - glycosyltransferases; that catalyze purine or pyrimidine nucleosides formation from cheaper precursors. Microorganisms provide a wide range of related enzymes with differential substrate tolerance and lower costs. - lipases; pharmacological properties of nucleosides can, in principle, be improved by acylating selectively the sugar hydroxyls. These prodrugs can be synthesized by using lipases, which are cheap and commercially available enzymes. - phosphatases; nucleoside phosphates can be obtained enzymatically, using whole cells. - immobilized biocatalysts; developed simplify scale up processes. These methodologies have been applied to nucleosides of interest and some relevant results are shown in this poster. In addition, the synthesis of modified oligonucleotides is also carried out in our lab. The preparation and properties of a nuclease resistant ribozyme is also shown in this work.