Helix induction by dirhodium: access to biocompatible metallopeptides with defined secondary structure.

The use of carboxylate side chains to induce peptide helicity upon binding to dirhodium centers is examined through experimental and computational approaches. Dirhodium binding efficiently stabilizes alpha helicity or induces alpha helicity in otherwise unstructured peptides for peptides that contain carboxylate side chains with i, i+4 spacing. Helix induction is furthermore possible for sequences with i, i+3 carboxylate spacing, though in this case the length of the side chains is crucial: ligating to longer glutamate side chains is strongly helix inducing, whereas ligating the shorter aspartate side chains destabilizes the helical structure. Further studies demonstrate that a dirhodium metallopeptide complex persists for hours in cellular media and exhibits low toxicity toward mammalian cells, enabling exploitation of these metallopeptides for biological applications.