Theoretical study on the inhibition of ribonucleotide reductase by 2 '-mercapto-2 '-deoxyribonucleoside-5 '-diphosphates

• Tipo: Artigo em Revista Científica Internacional
• Data: 2005

Autores

Pereira, S (Autor) Outra; Fernandes, PA (Autor) FCUP; Ramos, MJ (Autor) FCUP

Revista

Título: Journal of the American Chemical Society

Vol. 127 Nº 41

Páginas: 5174-5179

ISSN: 0002-7863

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 18 Citações

Scopus - 18 Citações

Classificação Científica

FOS: Ciências exactas e naturais > Química

Outras Informações

ID Authenticus: P-000-3VJ

DOI: 10.1021/ja046662w

Abstract (EN): Ribonucleotide reductase (RNR) is responsible for the reduction of ribonucleotides into the correspondent 2'-deoxyribonucleotides in the only physiological process that yields the monomers of DNA. The enzyme has thus become an attractive target for chemotherapies that fight proliferation-based diseases, specifically cancer and infections by some viruses and parasites. 2'-Mercapto-2'-deoxyribonucleoside-5'-diphosphates (SHdNDP) are mechanism-based inhibitors of RNR and therefore potential chemotherapeutic agents for those indications. Previous experimental studies established the in vitro and in vivo activity of SHdNDP. In the in vitro studies, it was observed that the activity was dependent on the oxidative status of the medium, with the inactivation of RNR only occurring when molecular oxygen was available. To better understand the mechanism involved in RNR inactivation by SHdNDP, we performed theoretical calculations on the possible reactions between the inhibitors and the RNR active site. As a result, we propose the possible mechanistic pathways for the chemical events that occur in the absence and in the presence of O-2. They correspond to a refinement and a complement of those proposed in the literature.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 6