Interactions of water soluble porphyrins with Z-poly(dG-dC)

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Abstract
The water soluble porphyrin tetrakis(4-N-methylpyridyl)porphine (H 2 TMpyP) and its copper(ll) derivative (CuTMpyP) convert Z-poly(dG-dC) to the B-form. For H 2 TMpyP, the fraction Z character (fr-Z) is given by fr-Z=1.0–21 r 0 and for CuTMpyP, fr-Z=.94–12 r o where r O s [Porphyrin] O /[DNA] O . Neither the manganese(lll) derivative of this porphyrin (MnTMpyP) nor tetrakis(2-N-methylpyridyl)porphine (H2TMpyP-2) is nearly as effective at causing the conversion. The former two porphyrins have been shown to intercalate into B-poly(dG-dC) whereas the latter two porphyrins do not. The kinetics of the Z→B conversion are independent of porphyrin or poly(dG-dC) concentration for 1/r O >6. At smaller values of 1/r O , the conversion rate is greatly increased for H 2 TMpyP and CuTMpyP. The interaction of these porphyrins with Z-poly(dG-dC) follows simple first order kinetics in this latter concentration range. It is proposed that for small values of 1/r O the sequence of events begins with a porphyrin-unassisted distortion of the Z-duplex (with a rate constant of 0.6 s'1) followed by a rapid uptake of porphyrin in what may be an intercalative mode. The porphyrin thus located in Z-regions brings about rapid conversion to the B-form. Binding of H2TMpyP or CuTMpyP to B-regions of a predominantly Z-strand leads to conversion of Z to B. However, this conversion process is considerably slower than when the porphyrins bind directly to Z-regions.