Monoalkylation of DNA by reductively activated FR66979.
Bioorg Med Chem
; 8(1): 173-9, 2000 Jan.
Article
em En
| MEDLINE
| ID: mdl-10968276
ABSTRACT
The antitumor antibiotic FR66979 has previously been shown to form interstrand cross-links in duplex DNA at the sequence [5'-d(CG)]2, linking the exocyclic amino groups (N2) of deoxyguanosine (dG) residues. During the reaction of reductively activated FR66979 with DNA. products are formed which have electrophoretic mobility in denaturing polyacrylamide gels which is intermediate between that of unmodified and interstrand cross-linked DNA. We show here that these products are monoadducts between FR66979 and DNA and provide strong evidence for the site of alkylation being N2 of dG. Moreover, the sequence selectivity of monoalkylation reactions between FR66979 and DNA containing either 5'-d(CG).5'-d(CI) or [5'-d(CG)]2 was observed to be ca. 5-fold less than for the related antitumor antibiotic mitomycin C (MC). The mechanistic implications of this result are discussed. Furthermore, it was demonstrated that contrary to a previous report, FR66979 requires DNA to be in duplex form for efficient monoadduct formation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxazinas
/
DNA
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos