Intelligent compounds which read DNA base sequences

Abstract

We have studied the DNA binding and DNA cleavage specificities of two novel classes of synthetic DNA breakage agents. One class comprises redox-activated metalloporphyrins, the other uses the photoactivable p-nitrobenzoyl group as the DNA breaking moiety linked covalently to a DNA recognizing entity such as an oligo N-methylpyrrolecarboxamide or oligothiazole group. Studies of DNA cleavage using end-labeled DNA restriction fragments and high resolution sequencing gel electrophoresis have allowed DNA break sites to be identified at the nucleotide level. This work in conjunction with induced CD spectroscopy has shown that these compounds, especially photoactive agents containing thiazole units, display high sequence specificity. The mechanism of sequence recognition appears to be quite different for the two series of compounds.