A pyrene dihydrodioxin with pyridinium 'arms': A photochemically active DNA cleaving agent with unusual duplex stabilizing and electron trapping properties

摘要

Pyrene dihydrodioxins (PDHD) comprise effective DNA intercalation agents that are masked orthoquinones, which can be released by near ultraviolet or visible irradiation. We have studied the binding and photoreactions of chiral dipyridinium PDHDs with herring sperm DNA and an 11-mer duplex DNA containing all 10 basepair steps. Binding affinities to herring sperm DNA were determined for purified enantiomers (K-b = 1.6 +/- 0.15 x 10(5) and 2.3 +/- 0.2 x 10(5) M-1). UV-melting experiments using the 11-mer DNA revealed significant stabilization of duplex DNA, (Delta T-m = 11.5 degrees and Delta T-m = 15.3 degrees C). Both enantiomers linearized (double-strand cleavage) supercoiled Phi X174 plasmid DNA with high efficiency. PDHDs have specificity to cleave and/or damage DNA duplexes at Gs and have preferable binding to GG DNA sites.