Tunable DNA cleavage by intercalating peptidoconjugates.
The properties of a novel family of peptide-based DNA-cleavage agents are described. Examination of the DNA-cleavage activities of a systematic series of peptide-intercalator conjugates revealed trends that show a strong dependence on peptide sequence. Conjugates differing by a single residue displayed reactivities that varied over a wide range. The cleavage activity was modulated by the electrostatic or steric qualities of individual amino acids. Isomeric conjugates that differed in the position of the tether also exhibited different reactivities. The mechanism of DNA cleavage for these compounds was also probed and was determined to involve hydrogen-atom abstraction from the DNA backbone. Previous studies of these compounds indicated that amino acid peroxides were the active agents in the cleavage reaction; in this report, the chemistry underlying the reaction is characterized. The results reported provide insight into how peptide sequences can be manipulated to produce biomimetic compounds.