Enhancing the specificity of peptide-nucleic acid binding with DNA

The specificity of peptide-nucleic acid (PNA) binding with DNA could be enhanced at the expense of lower thermal stability of nonspecific PNA-DNA complexes. Using a model complex of TTCTTCTTTT PNA and phage λ DNA, the bulk of nonspecific complexes were shown to dissociate at lower temperatures. However, some nonspecific complexes had almost the stability as the specific ones. The DNA sites admitting such stable nonspecific complexes were located; sequence analysis suggested that these were DNA stretches with terminal mismatches. The technique for locating PNA-DNA binding sites was improved to permit handling of long DNA molecules (up to 50 kbp).