Interaction of mithramycin with DNA. Evidence that mithramycin binds to DNA as a dimer in a right-handed screw conformation.
The CD and fluorescence properties of mithramycin have been used to follow its complexation to cations such as Mg2+ and Zn2+ and the binding of these complexes to DNA. At low concentration (less than 2 microM) in aqueous solution, mithramycin is always in the dimeric state, the conformation of the dimer being either a right-handed screw when the dimer is neutral, or a left-handed screw when the dimer is negatively charged. In the deprotonated state the dimer can bind one cation forming a complex [M2+(Mit-)2] which has a right-handed screw conformation. The stability constants of the complex at 37 degrees C in 0.1 M KCl are 4 x 10(5) and 1 x 10(6) for Mg2+ and Zn2+, respectively. The complex in the right-handed screw conformation binds DNA. In this case the stability constants of the complex [M2+ (Mit-)2] increase and are 3.6 x 10(6) and 1.2 x 10(7) for Mg2+ and Zn2+, respectively.
Demicheli
C
C
LPCB, CNRS, URA 198, Unité de Formation et de Recherche en Santé, Médecine et Biologie Humaine, Bobigny, France.
Albertini
J P
JP
Garnier-Suillerot
A
A
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008274:Magnesium; D008968:Molecular Conformation; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D008926:Plicamycin / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc
D004247:DNA; D008274:Magnesium; D015032:Zinc; D008926:Plicamycin