Application of ODMR to the study of DNA complexes of bisintercalating antibiotics and their biosynthesized derivatives

The DNA complexes of triostin A, echinomycin, and the monoquinoline (1QN) and bisquinoline (2QN) biosynthesized derivatives of echinomycin were investigated by optical detection of triplet-state magnetic resonance (ODMR) spectroscopy, with the quinoxaline and quinoline moieties of the DNA-binding peptides used as intrinsic probes. Plots of zero-field splitting (zfs)D parameter versus monitored wavelength revealed heterogeneity in the phosphorescence emission of echinomycin, triostin A, and 2QN ascribed to the occurrence of major and minor forms of the peptides in aqueous solution. ODMR results, in conjunction with findings from phosphorescence studies, indicate that the quinoxaline and quinoline chromophores of the major forms of the peptides are involved in aromatic stacking interactions in complexes with the natural DNAs fromMicrococcus lysodeikticus, Escherichia coli, and calf thymus as evidenced by red shifts in the phosphorescence 0,0 bands of the drugs, reductions in the phosphorescence lifetimes and zfsD andE parameters, and polarity reversal of the ODMR slow passage signals upon drug complexation. The reversal in ODMR signal polarity of echinomycin and 2QN is a consequence of changes in the triplet-state sublevel decay constants upon peptide binding to the natural DNAs. The extent of reduction of theD parameter for the major form of echinomycin, 2QN, and the quinoline moiety of 1QN upon complexation with polymeric DNAs was found to correlate with the binding affinities measured for these targets [1], but no correlation was found for the quinoxaline moiety of 1QN. Preliminary studies of triostin A-DNA complexes also revealed no correlation between the reduction in zfsD-value upon complexation and binding affinity, although the largest reductions inD-value among the peptides investigated in this report were exhibited by the poly(dG-dC)·poly(dG-dC) and natural DNA complexes of triostin A.