Artificial, Photoactivatable Amino Acids for Crosslinking Proteins in Living Cells

Protein-protein interactions are the key to organizing cellular processes in space and time.  The only direct way to identify such interactions in their cellular environment is by photo-cross-linking.  Scientists from the Max Planck Institute of Molecular Cell Biology and Genetics present a new strategy for photo-cross-linking proteins in living cells.  They designed two new photoactivatable amino acids that were termed photo-methionine and photo-leucine based on their structures and properties closely resembling the natural amino acids methionine and leucine, respectively.  This similarity allows them to escape the stringent identity control mechanisms during protein synthesis and be incorporated into proteins by the unmodified mammalian translation machinery.  Activation by ultraviolet light induces covalent cross-linking of the interacting proteins, which can be detected with high specificity, e.g., by simple western blotting.

Suchanek M, Radzikowska A, Thiele C.   Photo-leucine and photo-methionine allow identification of protein-protein interactions in living cells.
Nature Methods. 2005 Apr;2(4):261-7.

WO2006/094745 A1