A non-classical intercalation model for a bleomycin amplifier.
The bleomycin amplifier 1 is sterically hindered and twisted about the torsional bond joining the two aromatic rings. The intercalation of 1 and its sterically unhindered isomer 2 with DNA has been studied using n.m.r., viscometric titrations of superhelical and linear DNA, and flow dichroism. Based on the unusually strong interaction of 1 with DNA base pairs, a non-classical intercalation model for this compound is proposed. The intrinsic twists of both the unfused biaromatic system of 1 and the hydrogen-bonded DNA base pairs are retained in the intercalator-DNA complex, and the methyl group of 1 is accommodated between the hydrogen bonded bases. The complex of 1 is the first example found to date of this type of intercalation of the methyl group with DNA. The structure-activity relationships as bleomycin amplifiers for 1, 2 and similar derivatives is discussed.
D001761:Bleomycin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D007364:Intercalating Agents / Q000494:pharmacology*; D008961:Models, Structural; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship
D007364:Intercalating Agents; D001761:Bleomycin; D004247:DNA