The interaction of unfused polyaromatic heterocycles with DNA: intercalation, groove-binding and bleomycin amplification.
A number of unfused-aromatic cations have been found to bind to DNA by intercalation and to amplify the bleomycin catalysed cleavage of DNA. These molecules are more similar in structure to unfused minor-groove binding compounds such as netropsin and DAPI than to fused-ring intercalators such as proflavine. An analysis of DAPI interactions with specific sequence DNA polymers has indicated that the binding modes for the molecule are sequence dependent: minor groove binding in sequences of three or more AT base pairs and intercalation in mixed or pure GC base pair sequences. As with other unfused intercalators which bind with their cationic side chains in the major groove, the amidinium groups of DAPI are in the major groove in the GC intercalation complex. DAPI is, thus, a good bleomycin amplifier in GC sequences but its minor-groove binding mode in AT sequences leads to bleomycin inhibition.
Department of Chemistry, Georgia State University, Atlanta 30303.
W D
WD
Wilson
F A
FA
Tanious
H J
HJ
Barton
R L
RL
Wydra
R L
RL
Jones
D W
DW
Boykin
L
L
Strekowski
D001483:Base Sequence; D001665:Binding Sites; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D004347:Drug Interactions; D006571:Heterocyclic Compounds / Q000378:metabolism*; D007364:Intercalating Agents / Q000378:metabolism*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
D006571:Heterocyclic Compounds; D007364:Intercalating Agents; D001761:Bleomycin; D004247:DNA