Porphyrin and metalloporphyrin binding to DNA polymers: rate and equilibrium binding studies

Interactions of meso-tetrakis(4-N-methylpyridiniumyl)porphyrin TMpyP(4)] with polyd(G-C)].polyd(G-C)] polyd(G-C)2] and polyd(A-T)].polyd(A-T)] polyd(A-T)2] were studied by equilibrium dialysis and stopped-flow dissociation kinetics as a function of Na+]. Metalloderivatives of TMpyP(4), NiTMpyP(4), and ZnTMpyP(4) were also investigated. The apparent equilibrium binding constants (Kobs) were approximately the same for TMpyP(4) binding to either polyd(G-C)2] or polyd(A-T)2] and decreased with increasing Na+]. The slopes of the plots of log Kobs vs log Na+] were similar, with values close to -2.7. Contrary to implications in previously reported studies, these data do not indicate that TMpyP(4) prefers to bind to GC sites at low ionic strength and to AT sites at high ionic strength. In contrast, binding of ZnTMpyP(4) to these two polymers is very different. Comparisons of Kobs values at 0.065 M Na+] indicate that ZnTMpyP(4) binding to AT sites is approximately 200 times more favorable than binding to GC sites, a finding in agreement with previous qualitative observations. Although the binding of the Zn species to the GC polymer was too weak for us to assess the salt effect, the plot of log Kobs vs log Na+] gave a slope of -2.0 for ZnTMpyP(4) binding to polyd(A-T)2]. Application of condensation theory for polyelectrolytes suggests similar charge interactions for ZnTMpyP(4) and for TMpyP(4) binding to polyd(A-T)2]. Likewise, the rates of dissociation from polyd(A-T)2] were similar for TMpyP(4) and ZnTMpyP(4) and also NiTMpyP(4)]. However, whereas TMpyP(4) and NiTMpyP(4)] dissociation from polyd(G-C)2] was measurable, that for ZnTMpyP(4) was too fast to measure.(ABSTRACT TRUNCATED AT 250 WORDS)