DNA-ligand interactions studied through the chiral nature of DNA

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DAN base-sequence recognition by DNA ligands is one of the most fundamental and important issues in every life forms. To understand DNA-ligand interactions at the molecular level, we have been working on low molecular-weight metal complexes, especially achiral metal porphyrin complexes as they exhibit substantial induced CD in the Soret band region. We have previously revealed that induced CD spectra reflect various binding modes such as major groove binding, minor groove binding and intercalation between base-pairs of DNA.To obtain quantitative information on the binding modes, we have adopted two independent methods. One is based on the genetic algorithm combined with the steepest descent technique, and the other is based on more empirical approach by normalizing induced CD spectra recorded at different r (r=[porphyrin]/[DNA]) values by [DNA]. The former involved substantial computer programming using c-language. Without adopting the usual Lorentzian or Gaussian curves, the spectra were simulated with general forms with t-distribution against light energy. The number of components was determined by the degree of reduction of errors. Generally speaking, simulation was successful and we are currently writing a new program which calculates site sizes and binding constants based on the simulated CD curves. The other method involved only three components at maximum. Despite the small numbers of components, the simulation was good.To extend the process to other systems especially to DNA-binding proteins, we have synthesized conjugated with a peptide or amino acid residue.