Sequence-specific inhibition of a designed metallopeptide catalyst

Rhodium metallopeptides catalyze proximity-driven modification of peptide and protein substrates with enzyme-like selectivity. In this communication, we demonstrate that designed metallopeptide catalysts can be inhibited in a sequence-specific manner, mimicking the inhibition and regulation of natural enzymes. We demonstrate sub-micromolar inhibition by a histidine-containing inhibitor peptide, taking advantage of cooperative supramolecular assembly and inorganic coordination.