ASSESSING THE SEQUENCE SPECIFICITY IN THE BINDING OF CO(III) TO DNA VIA A THERMODYNAMIC APPROACH

The interaction specificities of Co (III) with DNA were investigated v ia consideration of thermodynamic characteristics of the duplex to sin gle strand transition for DNA oligomers incubated in the presence of [ Co(NH3)(5)(OH2)](ClO4)(3). It has previously been demonstrated that in cubation of the DNA oligomer [(5medC-dG)(4)](2) with this cobalt compl ex leads to coordination of the cobalt center to the DNA, presumably a t N7 of guanine bases [D. C. Calderone, E. J. Mantilla, M. Hicks, D. H . Huchital, W. R. Murphy, Jr. and R. D. Sheardy, (1995) Biochemistry 3 4, 13841]. In this report, DNA oligomers of different sequence were in cubated with [Co(NH3)(5)(OH2)](ClO4)(3) via protocols developed previo usly and the treated oligomers were subjected to thermal denaturation for comparison to the untreated oligomers. The DNA oligomers were desi gned in order to investigate the sequence specificity, if any, in the reaction of the cobalt complex with DNA. The values of T-m, Delta H-nu H, and Delta n (the differential ion binding term) obtained from the thermal denaturations were used to assess the sequence specificity of the interaction. For all oligomers, treated or untreated, T-m and Delt a H-nu H vary linearly with log [Na+] and hence the value of an is a f unction of the Na+ concentration. The results indicate no significant reaction between the cobalt complex and oligomers possessing isolated -GA- or -CG- sites; however, the thermodynamic characteristics of DNA oligomers possessing either an isolated -GG- site or an isolated -GC- site were altered by the treatment. Atomic absorption studies of the t reated oligomers demonstrate that only the DNA oligomers possessing is olated -GG- or -GC- sites bind cobalt. Hence, the changes in the therm odynamic properties of these oligomers are a result of cobalt binding with a remarkable sequence specificity. (C) 1997 John Wiley & Sons, In c.