Photo-leucine, as well as another photo-reactive amino acid derived from methionine, photo-methionine, were first synthesized in 2005 by Monika Suchanek, Anna Radzikowska and Christoph Thiele[2] from the Max Planck Institute of Molecular Cell Biology and Genetics with the objective of identifying protein to protein interaction throughout a simple western blot test that would provide high specificity.

The resemblance of the photo-reactive amino acids to the natural ones allows the former to avoid the extensive control mechanisms that take place during the protein synthesis within the cell.

This new way of synthesizing photo-leucine requires boc-(S)-photo-leucine, which is prepared via ozonolysis of a commercially available product, followed by formation of the diazirine by de method of Church and Weiss.

This route supposes a significant improvement over the original six-step synthesis of (S)-photo-leucine, which proceeded in low yield and required enzymatic resolution of a racemic intermediate.

In the absence of the original amino acid (l-leucine) in an environment, l-photo-leucine is used just as its naturally occurring analog in the protein processing mechanisms of the cell.

Photo-affinity labeling is a powerful tool to identify protein targets of biologically active small molecules and to probe the structure of ligand binding sites, reason due to which photo amino acids, including photo-leucine, are so useful.

Monika Suchanek, Anna Radzikowska and Christoph Thiele carried out an experiment in which they had successfully managed to label proteins from the cells of a monkey's kidney (COS7).

At about 70% of confluence, the initial medium was replaced by another one lacking the amino acids methionine, leucine, isoleucine and valine, as well as phenol red.

Once the time was over, cells were washed using PBS and UV-irradiated using a 200-W high pressure mercury lamp with a glass filter that removed wavelengths under 310 nm during 1 to 3 minutes.

[4] Traditionally, the recognition of protein-protein interactions was carried out through chemical cross-linking, that involved the use of moderately reactive bifunctional reagent, commonly attached to free amino groups.

However, currently photo-reactive amino acids are used in combination with chemical cross-linkers in order to achieve the most reliable results possible within protein-protein interaction studies.