INTELLIGENT COMPOUNDS WHICH READ DNA-BASE SEQUENCES

We have studied the DNA binding and DNA cleavage specificities of two novel classes of synthetic DNA breakage agents. One class comprises re dox-activated metalloporphyrins, the other uses the photoactivable p-n itrobenzoyl group as the DNA breaking moiety linked covalently to a DN A recognizing entity such as an oligo N-methylpyrrolecarboxamide or ol igothiazole group. Studies of DNA cleavage using end-labeled DNA restr iction fragments and high resolution sequencing gel electrophoresis ha ve allowed DNA break sites to be identified at the nucleotide level. T his work in conjunction with induced Co spectroscopy has shown that th ese compounds, especially photoactive agents containing thiazole units , display high sequence specificity. The mechanism of sequence recogni tion appears to be quite different for the two series of compounds.