Role of Mg2+ in the interaction of anticancer antibiotic, chromomycin A(3)with DNA: Does neutral antibiotic bind DNA in absence of the metal ion?

Antitumor antibiotic, Chromomycin A(3) (CHR), inhibits DNA replication and transcription Via reversible interaction with double stranded DNA with GC-b ase specificity. The interaction, at and above physiological pH, requires t he presence of bivalent metal ions, such as Mg2+. Anionic antibiotic does n ot bind DNA in the absence of Mg2+. In this paper we have examined the stru ctural potential of neutral CHR at pH 5.2 to bind DNA in the absence of Mg2 +. We have demonstrated the ability of the neutral antibiotic to bind DNA by m eans of different spectroscopic techniques and evaluated the necessary ther modynamic parameters for elucidation of the molecular basis of recognition. The results are compared with the scenario when Mg2+ is present in the sys tem, because the ultimate aim of these studies is to elucidate the role of Mg2+ in CHR-DNA recognition. Neutral CHR binds to Mg2+ with lesser affinity than its anionic form. Spect roscopic features of the drug and its Mg2+ complex indicate self associatio n of the antibiotic in the absence and presence of Mg2+. GC-base specificit y of the drug and its Mg2+ complex are retained at pH 5.2, though the modes of recognition of DNA by the two ligands are different. Minor groove width of DNA plays a role in the accommodation of the ligand(s) during the GC ba se specific recognition while positive charge of Mg2+ in CHR:Mg2+ complex f urther facilitates the association. Relatively lower affinity of the neutra l drug and its Mg2+ complex for DNA can be ascribed to the self association of these ligands in the absence of DNA.