An NMR study of [d(CGCGAATTCGCG)]2 containing an interstrand cross-link derived from a distamycin-pyrrole conjugate.
Nucleic Acids Res
; 24(8): 1566-73, 1996 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-8628693
ABSTRACT
Minor groove binding compounds related to distamycin A bind DNA with high sequence selectivity, recognizing sites which contain various combinations of A.T and G.C base pairs. These molecules have the potential to deliver cross-linking agents to the minor groove of a target DNA sequence. We have studied the covalent DNA-DNA cross-linked complex of 2,3- bis(hydroxymethyl)pyrrole-distamycin and [d(CGCGAATTCGCG)]2. The alkylating pyrrole design is based on the pharmacophore of mitomycin C and is similar in substructure to another important class of natural products, the oxidatively activated pyrrolizidine alkaloids. Ligand-DNA NOEs confirm that the tri(pyrrole-carboxamide) unit of the ligand is bound in the minor groove of the central A+T tract. Unexpectedly, it is shifted by 1 bp with respect to the distamycin A binding site on this DNA sequence. The cross-link bridges the 2-amino position of two guanine residues, G4 and G22. The C3.G22 and G4.C21 base pairs exhibit Watson-Crick base pairing, with some local distortion, as evidenced by unusual intensities observed for DNA-DNA NOE cross-peaks. The model is compared with a related structure of a cross-linked mitomycin CDNA complex.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligodesoxirribonucleotídeos
/
Pirróis
/
DNA
/
Distamicinas
Idioma:
En
Revista:
Nucleic Acids Res
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Estados Unidos