DNA binding properties of FCE24517, an electrophilic distamycin analogue.
Anticancer Drug Des
; 7(2): 131-41, 1992 Apr.
Article
en En
| MEDLINE
| ID: mdl-1575886
The distamycin derivative FCE24517 binds both reversibly and irreversibly to DNA. At 37 degrees C, the drug originates reversible complexes that are strong enough to survive to the electrophoretic separation of the substrate. These complexes slowly evolve to covalent adducts (10(-4) adducts/bp/h) that eventually degenerate to single-strand breaks (1.5 x 10(-5) nicks/bp/h). The site of attack by the drug can be any base in the vicinity of AT-rich regions of the double helix. Rapidly reassociating duplex DNA molecules, indicative of the presence of cross-links, are observed only upon boiling of DNA with FCE24517. While the low rates of formation of covalent adducts and DNA breaks could be relevant for the long-term biological effects of FCE24517, the specific formation of strong but still reversible complexes with DNA could be matched to the drastic and sudden reduction of thymidine incorporation induced by this electrophilic distamycin.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
ADN
/
Distamicinas
/
Antineoplásicos
/
Compuestos de Mostaza Nitrogenada
Idioma:
En
Revista:
Anticancer Drug Des
Asunto de la revista:
ANTINEOPLASICOS
/
FARMACOLOGIA
Año:
1992
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos