A unique binding cavity for divalent cations in the DNA–metal–chromomycin A3 complex

✍ Scribed by Laura Itzhaki; Sarah Weinberger; Nurit Livnah; Elisha Berman

• Publisher: Wiley (John Wiley & Sons)
• Year: 1990
• Tongue: English
• Weight: 641 KB
• Volume: 29
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.360290303

✦ Synopsis

Abstract

Binding of chromomycin A~3~ (CRA) to calf thymas DNA was investigated in the presence of divalent cations using visible absorption and ^1^H‐nmr spectroscopies. An apparent equilibrium binding constant (∼ 10^11^M^−1^) was obtained from metal competition experiments using EDTA to remove the metal cation from the DNA–M–CRA (M: metal) complex. The large binding constant of the drug to DNA enabled us to obtain essentially complete complexation of CRA to the short homogeneous d(ATGCAT)~2~ duplex using stoichiometric amounts of the metal cation. Large induced chemical shifts were observed in the ^1^H‐nmr spectrum of the above complex using the paramagnetic Co^2+^ cation indicating that the metal occupies a unique binding site. Since no induced ^1^H‐nmr chemical shifts were observed for the drug–Co^2+^ mixture, it was concluded that no metal–drug complex is formed. In addition, it was found that bound CRA is negatively charged at physiological pH and binding to the DNA could be affected only by using metal cations whose ionic radius size (< 0.85 Å) and charge (2+) were simultaneously satisfied. Stringent metal cation selectivity for the DNA–M–CRA complex may be intimately connected with the antitumor selectivity of CRA, since different types of cells generally possess widely differing molar concentrations of metal cations.