Azobenzene derivatives can be used to reversibly photo-regulate conformation and activity when introduced as intramolecular bridges in peptides and proteins. Here we report the design, synthesis, and characterization of an azobenzene derivative that absorbs between 400-450 nm in aqueous solution to produce the cis isomer, and relaxes back to the trans isomer with a half-life of a few seconds at room temperature. In the trans form, the linker can span a distance of approximately 25 A, so that it can bridge Cys residues spaced i, i + 15 in an alpha-helix. Switching of the azobenzene cross-linker from trans to cis causes a decrease in the helix content of peptides where the linker is attached via Cys residues spaced at i, i + 15 and i, i + 14 positions, no change in helix content with Cys residues spaced i, i + 11 and an increase in helix content in a peptide with Cys residues spaced at i, i + 7. In the presence of 10 mM reduced glutathione, the azobenzene cross-linker continued to photo-switch after 24 hours. This cross-linker design thus expands the possibilities for fast photo-control of peptide and protein structure in biochemical systems.