Using an azobenzene cross-linker to either increase or decrease peptide helix content upon trans-to-cis photoisomerization.

Reversible photocontrol of peptide and protein conformation could prove to be a powerful tool for probing function in diverse biological systems. Here, we report reversible photoswitching of the helix content in short peptides containing an azobenzene cross-linker between cysteine residues at positions i, i + 4, or i, i + 11 in the sequence. Trans-to-cis photoisomerization significantly increases the helix content in the i, i + 4 case and significantly decreases the helix content in the i, i + 11 case. These cross-linker designs significantly expand the possibilities for photocontrol of peptide and protein structure.