Oehlers Leon, Mazzitelli Carolyn L, Brodbelt Jennifer S, Rodriguez Mireya, Kerwin Sean
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712-0165, USA.
J Am Soc Mass Spectrom. 2004 Nov;15(11):1593-603. doi: 10.1016/j.jasms.2004.07.015.
Electrospray ionization mass spectrometry is used to compare the metal ion binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and benzimidazole (5) compounds and to elucidate the putative binding modes and stoichiometries. The observed metal versus non-metal-mediated DNA binding, as well as the specificity of DNA binding, is correlated with the biological activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal-mediated binding to DNA, with the appearance of DNA complexes containing multiple ligands. The anticancer analog 2 demonstrates a clear preference for metal-mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation between DNA and the biologically inactive analog 1 was not observed, either in the absence or presence of metal cations.
