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

Abstract

Th e DNA complexes of triostin A, echinomycin, and the monoquinoline (ION) and bisquinoline (20N) biosynthesized derivatives of echinomycin were investigated by optic띠 detection of triplet-state magnetic resonance (ODMR) spectroscopy, with the quinox따ine and q띠noline 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 20N ascribed to the occurren,:e of m혀or and minor forms of the peptides in aqueous solution. ODMR results, in co띠unctIOn with findings from phosphorescence studies, indicate that the quinox외ine and quinoline chromophores of the major forms of the peptides are involved in aromatic stacking interactions in complexes with the natural DNAs from Micrococcus ωodeiktic따; 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 zfs D and E parameters, and p이arity reversal of the ODMR slow passage signals upon drug complexation. The reversal in ODMR signal pol따ity of echinomycin 뻐d 20N is a consequence of changes in the triplet-state sublevel decay constants upon peptide binding to the natural DNAs. Th e extent of reduction of the D parameter for the major form of echinomycin, 20N, and the quinoline moiety of ION upon complexation with polymeric DNAs was found to correlate with the binding a떠nities measured for these targets [1], but no correlation was found for the quinox외ine moiety of ION. Preliminary studies of triostin A-DNA complexes also revealed no correlation between the reduction in zfs D-value upon complexation and binding affinity, although the largest reductions in D-value among the peptides investigated in this report were exhibited by the poly(dG-dC) ' poly(dGdC) and natural DNA complexes of triostin A.

Phosphorescence and Optically Detected Magnetic Resonance Investigation of the Binding of the Nucleocapsid Protein of the Human Immunodeficiency Virus Type 1 and Related Peptides to RNA

“…Reversal in signal polarity is unusual, but it has been observed previously for tryptophan in the E. coli SSB complex with poly(dT) in which Trp54 undergoes a polarity reversal of its ODMR signals (Zang et al, 1987;Tsao et al, 1989). Polarity reversals of ODMR signals are also found for quinoxaline and quinoline chromophores in bis-intercalating peptide antibiotics upon being bound to DNA (Alfredson et al, 1989(Alfredson et al, , 1991a. In each case, the chromophore undergoes aromatic stacking interactions with the nucleic acid bases.…”