The Sal-XH Motif for Metal-Mediated Oxidative DNA−Peptide Cross-Linking

Metallopeptide motifs of the N-terminal sequence XXH, wherein histidine resides in the third position of the peptide, were first described for albumins and later utilized as redox-active bioconjugates for DNA cleavage and protein-protein cross-linking. Metallosalens are another class of tetradentate ligands that have seen applications to DNA chemistry. The juxtaposition of these two motifs leads to a Schiff-base metallopeptide hybrid that might combine the molecular recognition features of a peptide with the chemical reactivity of salicylaldimine complexes. Toward this end, we describe the synthesis and characterization of a prototypical member of this new "sal-XH" ligand class and an example of DNA-peptide cross-linking.