Synthesis of Photoreactive Aromatic α-Amino Acids and Effective Hydrogen-Deuterium Exchange for Aromatic α-Amino Acids

Abstract

Photoaffinity labeling is one of the favorite methods for chemical biology. The first step in this method is the construction of photophores and their modification to the associated high affinity target ligand. α-Amino acids have biological activities themselves and are fundamental component of peptides and protein. The photoreactive aromatic α-amino acids are useful for investigation of biological phenomenon. Although synthesis of photoreactive phenylalanine analogues has already been reported, there have been few reports of the synthesis of photoreactive tryptophan and side-chain elongated phenylalanine. We report here the effective photoreactive tryptophan and side-chain elongated phenylalanine derivatives. Furthermore, we report the mild and controllable hydrogen-deuterium exchange for aromatic hydrogen with trifluoromethanesulfonic acid-d during the course of the synthesis of side-chain elongated phenylalanine. These hydrogen-deuterium exchange properties for these aromatic α-amino acids are identical to those of the peptides. With this method the exchange proceeds significantly faster than previously described methods. Detail analysis of the exchange revealed that the method was controllable by temperature-, time-, and dose- dependent manner.