INGEBI   02650
INSTITUTO DE INVESTIGACIONES EN INGENIERIA GENETICA Y BIOLOGIA MOLECULAR "DR. HECTOR N TORRES"
Unidad Ejecutora - UE
capítulos de libros
Título:
Síntesis quimioenzimática de fosfatos y fosfotriésteres de nucleósidos
Autor/es:
ESTEBAN D. GUDIÑO; LUIS E. IGLESIAS; ELIZABETH S. LEWKOWICZ; ADOLFO M. IRIBARREN
Libro:
Biocatálise e Biotransformacao: Fundamentos e aplicacoes
Editorial:
Schoba
Referencias:
Año: 2014; p. 103 - 132
Resumen:
Many of the commercially available antiviral and antitumor drugs are nucleoside analogues. However, these compounds show poor bioavailability, are catabolically inactivated and in some cases the first phosphorylation needed to generate the active drug, the nucleoside 5´-monophosphates, is the metabolic step. One way to partially avoid these problems is the use of prodrugs. In this regard, the regioslective synthesis of 5´-phosphatidylnucleosides catalyzed by phospholipase D (PLD) can produce potential prodrugs with a non toxic structure and with high affinity for the cell membrane. Subsequent enzymatic hyrolysis with phospholipase C using these derivatives allows obtaining the corresponding nucleoside 5´-monophosphate by a simple purification step. On the other hand, dialkylphosphotriesters are potential lipophilic prodrugs which would avoid the first step of phosphorylation in vivo releasing the corresponding nucleoside monophosphate. These derivatives can be regioselectively obtained through a transesterification reaction catalyzed by phosphotriesterases carried out in anhydrous medium. To improve yelds of these reactions, medium engineering studies and expression of the eznyme is in progress.