5-Iodo-2'-deoxy-L-uridine and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine: selective phosphorylation by herpes simplex virus type 1 thymidine kinase, antiherpetic activity, and cytotoxicity studies. (Articolo in rivista)

Type

• Articolo in rivista (Classe)
• Prodotto della ricerca (Classe)

Label

• 5-Iodo-2'-deoxy-L-uridine and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine: selective phosphorylation by herpes simplex virus type 1 thymidine kinase, antiherpetic activity, and cytotoxicity studies. (Articolo in rivista) (literal)

Anno

• 1995-01-01T00:00:00+01:00 (literal)

Alternative label

• Spadari S, Ciarrocchi G, Focher F, Verri A, Maga G, Arcamone F, Iafrate E, Manzini S, Garbesi A, Tondelli L. (1995)
  5-Iodo-2'-deoxy-L-uridine and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine: selective phosphorylation by herpes simplex virus type 1 thymidine kinase, antiherpetic activity, and cytotoxicity studies.
  in Molecular pharmacology (Print)
  (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

• Spadari S, Ciarrocchi G, Focher F, Verri A, Maga G, Arcamone F, Iafrate E, Manzini S, Garbesi A, Tondelli L. (literal)

Pagina inizio

• 1231 (literal)

Pagina fine

• 1238 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

• 47 (literal)

Rivista

• Molecular pharmacology (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

• 6 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

• Istituto di Genetica Biochimica ed Evoluzionistica, Consiglio Nazionale delle Ricerche, Pavia, Italy. (literal)

Titolo

• 5-Iodo-2'-deoxy-L-uridine and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine: selective phosphorylation by herpes simplex virus type 1 thymidine kinase, antiherpetic activity, and cytotoxicity studies. (literal)

Abstract

• 5-Iodo-2'-deoxy-L-uridine (L-IdU) and (E)-5-(2-bromovinyl)-2'-deoxy-L-uridine (L-BVdU) have been prepared and found to inhibit herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with activities comparable to those of their analogs with the natural D-sugar configuration. The mechanism of inhibition is purely competitive for L-IdU (Ki = 0.24 microM) and mixed-type for L-BVdU (Ki = 0.13 microM). High performance liquid chromatographic analysis of the reaction products demonstrated that the viral enzyme phosphorylates both L-enantiomers to their corresponding monophosphates with efficiency comparable to that for D-enantiomers. Neither L-enantiomer inhibits the human cytosolic TK. In contrast to their D-enantiomers, L-IdU and L-BVdU have no effect on human thymidylate synthase, either in HeLa cells or in TK-deficient HeLa cells transformed with the HSV-1 TK gene. Both L-enantiomers (i) have no effect on HeLa cell growth, (ii) are 1000-fold less cytotoxic toward TK-deficient HeLa cells transformed with the HSV-1 TK gene than are their D-enantiomers, (iii) in contrast to their D-enantiomers, are fully resistant to hydrolysis by nucleoside phosphorylase, and, (iv) in spite of their much lower cytotoxicity, most probably due to the very low affinity of L-BVdU monophosphate and L-IdU monophosphate for thymidylate synthase, are only 1 or 2 orders of magnitude less potent than their D-enantiomers in inhibiting viral growth, with potency comparable to that of acyclovir. (literal)

Prodotto di

• Institute of molecular genetics (IGM) (Istituto)

Autore CNR

• ANNA MARIA GARBESI (Unità di personale interno)
• GIOVANNI MAGA (Unità di personale interno)
• FEDERICO FOCHER (Unità di personale interno)
• SILVIO SPADARI (Unità di personale interno)
• GIOVANNI CIARROCCHI (Persona)
• LUISA TONDELLI (Persona)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)

Autore CNR di

• GIOVANNI MAGA (Unità di personale interno)
• LUISA TONDELLI (Persona)
• FEDERICO FOCHER (Unità di personale interno)
• SILVIO SPADARI (Unità di personale interno)
• ANNA MARIA GARBESI (Unità di personale interno)
• GIOVANNI CIARROCCHI (Persona)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

• Molecular pharmacology (Rivista)