Synthesis and DNA interaction of a mixed proflavine-phenanthroline Tröger base.
We report the synthesis of an asymmetric Tröger base containing the two well characterised DNA binding chromophores, proflavine and phenanthroline. The mode of interaction of the hybrid molecule was investigated by circular and linear dichroism experiments and a biochemical assay using DNA topoisomerase I. The data are compatible with a model in which the proflavine moiety intercalates between DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I cleavage experiments were carried out to investigate the sequence preference of the hybrid ligand and a well resolved footprint was detected at a site encompassing two adjacent 5'-GTC.5-GAC triplets. The sequence preference of the asymmetric molecule is compared to that of the symmetric analogues.
Baldeyrou
Brigitte
B
INSERM U-524 et Laboratoire de Pharmacologie antitumorale du Centre Oscar Lambret, Institut de Recherches sur le Cancer, Place de Verdun, F-59045 Lille, France.
Tardy
Christelle
C
Bailly
Christian
C
Colson
Pierre
P
Houssier
Claude
C
Charmantray
Franck
F
Demeunynck
Martine
M
D001392:Azocines / Q000138:chemical synthesis* / Q000737:chemistry; D001483:Base Sequence; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000737:chemistry; D007364:Intercalating Agents / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010618:Phenanthrolines / Q000737:chemistry*; D011370:Proflavine / Q000737:chemistry*; D059004:Topoisomerase I Inhibitors
D001392:Azocines; D007364:Intercalating Agents; D010618:Phenanthrolines; D059004:Topoisomerase I Inhibitors; D004247:DNA; D011370:Proflavine; D004264:DNA Topoisomerases, Type I