Dual Control of Peptide Conformation with Light and Metal Coordination

The design of a stimuli‐responsive peptide whose conformation is controlled by wavelength‐specific light and metal coordination is described. The peptide adopts a defined tertiary structure and its conformation can be modulated between an α‐helical coiled coil and β‐sheet. The peptide is designed with a hydrophobic interface to induce coiled coil formation and is based on a recently described strategy to obtain switchable helix dimers. Herein, we endowed the helix dimer with 8‐hydroxyquinoline (HQ) groups to achieve metal coordination and shift to a β‐sheet structure. It was found that the conformational shift only occurs upon introduction of Zn 2+ ; other metal ions (Cu 2+ , Fe 3+ , Co 2+ , Mg 2 , and Ni 2+ ) do not offer switching likely due to non‐specific metal‐peptide coordination. A control peptide lacking the metal‐coordinating residues does not show conformational switching with Zn 2+ supporting the role of this metal in stabilizing the β‐sheet conformation in a defined manner.