Enantioselectivity of ribonucleotide reductase: a first study using stereoisomers of pyrimidine 2'-azido-2'-deoxynucleosides. (Articolo in rivista)

Type

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

Label

• Enantioselectivity of ribonucleotide reductase: a first study using stereoisomers of pyrimidine 2'-azido-2'-deoxynucleosides. (Articolo in rivista) (literal)

Anno

• 2004-01-01T00:00:00+01:00 (literal)

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

• 10.1016/j.bcp.2004.05.002 (literal)

Alternative label

• Roy B; Verri A; Lossani A; Spadari S; Focher F; Mathe' C; Gosselin G; Aubertin AM; Lepoivre M; Perigaud C (2004)
  Enantioselectivity of ribonucleotide reductase: a first study using stereoisomers of pyrimidine 2'-azido-2'-deoxynucleosides.
  in Biochemical pharmacology
  (literal)

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

• Roy B; Verri A; Lossani A; Spadari S; Focher F; Mathe' C; Gosselin G; Aubertin AM; Lepoivre M; Perigaud C (literal)

Pagina inizio

• 711 (literal)

Pagina fine

• 718 (literal)

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

• 68 (literal)

Rivista

• Biochemical pharmacology (Rivista)

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

• 8 (literal)

Note

• ISI Web of Science (WOS) (literal)

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

• UMR 5625 CNRS-UM II, Université Montpellier II, case courrier 008, place E. Bataillon, 34095 Montpellier Cedex 5, France; Istituto di Genetica Molecolare IGM-CNR, CNR, Via Abbiategrasso 207, I-27100 Pavia, Italy; Unité 544 I.N.S.E.R.M.-Université L. Pasteur, Institut de Virologie de la Faculté de Médecine, 3, rue Koeberlé, 67000 Strasbourg, France (literal)

Titolo

• Enantioselectivity of ribonucleotide reductase: a first study using stereoisomers of pyrimidine 2'-azido-2'-deoxynucleosides. (literal)

Abstract

• In this paper, the enantioselectivity of ribonucleotide reductase (RNR, EC 1.17.4.1), a pivotal enzyme involved in DNA biosynthesis, was studied using the beta-d and beta-l stereoisomers of 2'-azido-2'-deoxynucleosides of uracil and cytosine. The corresponding 5'-diphosphate derivatives in the d-configuration have been extensively studied as mechanism-based inhibitors of the enzyme. The original l-enantiomers were synthesized and evaluated in vitro. In cell culture experiments, only the cytosine derivative with a d-configuration was found cytostatic and able to deplete dNTP pools in response to RNR inhibition. In the case of the uracil enantiomeric pair, this result correlates with an inefficient intracellular monophosphorylation as demonstrated in testing their substrate properties against human uridine-cytidine kinase 1. Regarding cytosine analogues, human deoxycytidine kinase was found to be able to phosphorylate both enantiomers with comparable efficiency but only the d-stereoisomer was active in human cell culture. The interaction of the beta-d and beta-l stereoisomers of 2'-azido-2'-deoxyuridine 5'-diphosphate with purified Escherichia coli RNR was also examined. Inactivation of the enzyme was only observed in the presence of the d-stereoisomer, demonstrating that RNR exhibits enantiospecificity with respect to the natural configuration of the sugar moiety, as far as 2'-azido-2'-deoxynucleotides are concerned. (literal)

Prodotto di

• Institute of molecular genetics (IGM) (Istituto)
• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)

Autore CNR

• FEDERICO FOCHER (Unità di personale interno)
• SILVIO SPADARI (Unità di personale interno)

Incoming links:

Prodotto

• Institute of molecular genetics (IGM) (Istituto)
• Sviluppo e meccanismo d'azione di analoghi nucleotidici e nucleosidici come composti antiproliferativi e antivirali : nuovi composti e nuovi bersagli per la terapia (ME.P04.004.001) (Modulo)

Autore CNR di

• FEDERICO FOCHER (Unità di personale interno)
• SILVIO SPADARI (Unità di personale interno)

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

• Biochemical pharmacology (Rivista)