Open AccessChromomycin A 3 binds to left‐handed poly(dG‐m 5 dC)
Author(s) -
SHAFER Richard H.,
ROQUES Bernard P.,
LePECQ JeanBernard,
DELEPIERRE Muriel
Publication year - 1988
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1988.tb14009.x
Subject(s) - chromomycin a3 , polynucleotide , circular dichroism , absorbance , chemistry , crystallography , dna , stereochemistry , z dna , biochemistry , chromatography , heterochromatin , chromatin
The interaction of chromomycin A 3 (an antitumor antibiotic) with right‐handed and left‐handed polynucleotides has been studied by absorbance, fluorescence, circular dichroism, 31 P‐NMR and 1 H‐NMR techniques. Binding to either the B form of poly(dG‐dC) or the Z form of poly(dG‐m 5 dC) shifts the absorbance maximum to higher wavelength and enhances the fluorescence of the drug. Circular dichroic spectra of solutions containing various concentrations of chromomycin A 3 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. 31 P‐NMR spectra of the chromomycin A 3 complex with the Z form of poly(dG‐m 5 dC) demonstrate that the Z conformation is retained in the drug complex up to one molecule drug/four base pairs. At Mg 2+ concentrations lower than that necessary to stabilize the left‐handed conformation of poly(dG‐m 5 dC) alone, 31 P analysis shows that chromomycin A 3 can bind simultaneously to both the B and Z conformations of poly(dG‐m 5 dC), with no effect on the B–Z equilibrium. These data demonstrate that chromomycin A 3 binds to left‐handed poly(dG‐m 5 dC) with retention of the left‐handed conformation up to saturating drug concentrations.