Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral agents. (Articolo in rivista)

Type

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

Label

• Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral agents. (Articolo in rivista) (literal)

Anno

• 1997-01-01T00:00:00+01:00 (literal)

Alternative label

• Verri, A. Focher, F. Priori, G. Gosselin, G. Imbach, J. Capobianco, M. Garbesi, A. Spadari, S. (1997)
  Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral agents.
  in Molecular pharmacology (Print)
  (literal)

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

• Verri, A. Focher, F. Priori, G. Gosselin, G. Imbach, J. Capobianco, M. Garbesi, A. Spadari, S. (literal)

Pagina inizio

• 132 (literal)

Pagina fine

• 138 (literal)

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

• 51 (literal)

Rivista

• Molecular pharmacology (Rivista)

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

• 1 (literal)

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

Titolo

• Lack of enantiospecificity of human 2'-deoxycytidine kinase: relevance for the activation of beta-L-deoxycytidine analogs as antineoplastic and antiviral agents. (literal)

Abstract

• We demonstrate that human 2'-deoxycytidine kinase (dCK) is a nonenantioselective enzyme because it phosphorylates beta-D-2'-deoxycytidine (D-dCyd), the natural substrate, and beta-L-2'-deoxycytidine (L-dCyd), its enantiomer, with the same efficiency. Kinetic studies showed that L-dCyd is a competitive inhibitor of the phosphorylation of D-dCyd with a Kl value of 0.12 microM, which is lower than the K(m) value for D-dCyd (1,2 microM). Chemical modifications of either the base or the pentose ring strongly decrease the inhibitory potency of L-dCyd, L-dCyd is resistant to cytidine deaminase and competes in cell cultures with the natural D-dCyd as substrate for dCK, thus reducing the incorporation of exogenous [3H]dCyd into DNA. L-dCyd had no effect on the pool of dTTP deriving from the salvage or from the de novo synthesis, does not inhibit short term RNA and protein syntheses, and shows little or no cytotoxicity. Our results indicate a catalytic similarity between human dCK and herpetic thymidine kinases, enzymes that also lack stereospecificity. This functional analogy underlines the potential role of dCK as activator of L-deoxycytidine analogs as antiviral and antineoplastic agents and lends support to the hypothesis that herpesvirus thymidine kinase might have evolved from a captured cellular dCK gene, developing the ability to phosphorylate thymidine and retaining that to phosphorylate deoxycytidine. (literal)

Prodotto di

• Institute of molecular genetics (IGM) (Istituto)
• Institute for organic syntheses and photoreactivity (ISOF) (Istituto)

Autore CNR

• SILVIO SPADARI (Unità di personale interno)
• ANNA MARIA GARBESI (Unità di personale interno)
• FEDERICO FOCHER (Unità di personale interno)
• MASSIMO CAPOBIANCO (Unità di personale interno)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Institute for organic syntheses and photoreactivity (ISOF) (Istituto)

Autore CNR di

• MASSIMO CAPOBIANCO (Unità di personale interno)
• FEDERICO FOCHER (Unità di personale interno)
• SILVIO SPADARI (Unità di personale interno)
• ANNA MARIA GARBESI (Unità di personale interno)

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

• Molecular pharmacology (Rivista)