Sequence-selective, pH-dependent binding to DNA of benzophenanthridine alkaloids.
The sequence selectivity associated with binding to DNA of three alkaloids belonging to the benzophenanthridine family has been analysed by DNase I footprinting, and the results were compared with those obtained from an analysis of the behaviour of the standard intercalator, ethidium bromide. Like the ethidium, the benzophenanthridine compounds appear to bind best to regions of mixed nucleotide sequence, especially those containing alternating purines and pyrimidines, although there are some notable differences in behaviour. There is also a marked lack of binding to sequences such as (AT)n, where n greater than or equal to 3. The binding to DNA of the benzophenanthridines is specifically related to the hydrogen ion concentration of the medium, in that the DNase I footprints are considerably enhanced when the reaction is performed at a pH below 7.0. We discuss these results in terms of a greater preponderance of the intercalating species being present at lower pH.
Bajaj
N P
NP
Department of Pharmacology, University of Cambridge Medical School, UK.
McLean
M J
MJ
Waring
M J
MJ
Smekal
E
E
D000470:Alkaloids / Q000378:metabolism*; D001483:Base Sequence; D053119:Benzophenanthridines; D004247:DNA / Q000378:metabolism*; D003850:Deoxyribonuclease I; D004996:Ethidium / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007364:Intercalating Agents / Q000378:metabolism; D007546:Isoquinolines; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010617:Phenanthridines / Q000378:metabolism
D000470:Alkaloids; D053119:Benzophenanthridines; D007364:Intercalating Agents; D007546:Isoquinolines; D010617:Phenanthridines; D004247:DNA; C005705:sanguinarine; C016299:chelerythrine; D003850:Deoxyribonuclease I; D004996:Ethidium