Molecular mechanism of the DNA sequence selectivity of 5-halo-2'-deoxyuridines as potential radiosensitizers.
J Am Chem Soc
; 132(42): 14710-3, 2010 Oct 27.
Article
em En
| MEDLINE
| ID: mdl-20886875
ABSTRACT
The 5-halo-2'-deoxyuridines bromodeoxyuridine (BrdU) and iododeoxyuridine (IdU) are well-known photosensitizers for inducing DNA/RNA-protein cross-linking and potential radiosensitizers for radiotherapy of cancer. The dependence of the photosensitivity of BrdU and IdU on the DNA sequence has been well-observed, but it is unknown whether there is a similar DNA sequence selectivity in their radiosensitivity. Here we show a new ultrafast electron transfer (UET) mechanism for the likely DNA sequence dependence of the radiosensitivity of BrdU and IdU. Our femtosecond time-resolved transient laser absorption spectroscopic measurements provide the first real-time observation of the UET reactions of BrdU/IdU with the anion states of adenine and guanine. It is shown that the UET between BrdU and dA*(-) (dA(-)) is more effective than that between BrdU and dG*(-). This is related to the recent observation that dG*(-) is highly destructive while dA(-) is long-lived. This mechanistic understanding may lead to the improvement of BrdU and IdU to achieve sufficient radiosensitizing efficacy and the development of more effective radiosensitizers for clinical uses.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Radiossensibilizantes
/
DNA
/
Desoxiuridina
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article