Chromomycin A3 binds to left‐handed poly(dG‐m5dC)

Abstract

The interaction of chromomycin A3 (an antitumor antibiotic) with right‐handed and left‐handed polynucleotides has been studied by absorbance, fluorescence, circular dichroism, 31P‐NMR and 1H‐NMR techniques. Binding to either the B form of poly(dG‐dC) or the Z form of poly(dG‐m5dC) shifts the absorbance maximum to higher wavelength and enhances the fluorescence of the drug. Circular dichroic spectra of solutions containing various concentrations of chromomycin A3 and fixed concentrations of either B or Z polynucleotides show well defined isoelliptic points at similar wavelengths. At the isoelliptic point, the drug complex with B DNA exhibits positive ellipticity while with ZDNA it exhibits negative ellipticity. 31P‐NMR spectra of the chromomycin A3 complex with the Z form of poly(dG‐m5dC) demonstrate that the Z conformation is retained in the drug complex up to one molecule drug/four base pairs. At Mg2+ concentrations lower than that necessary to stabilize the left‐handed conformation of poly(dG‐m5dC) alone, 31P analysis shows that chromomycin A3 can bind simultaneously to both the B and Z conformations of poly(dG‐m5dC), with no effect on the B–Z equilibrium. These data demonstrate that chromomycin A3 binds to left‐handed poly(dG‐m5dC) with retention of the left‐handed conformation up to saturating drug concentrations. Copyright © 1988, Wiley Blackwell. All rights reserved