Development of the Direct Deuteration Method for Amino Acids and Characterization of Deuterated Tryptophan

Proteins and peptides are essential biomolecules involved in the maintenance of biological functions and disease development. Their structural and functional analyses are crucial for drug discovery and pathology. Amino acids, the fundamental building blocks of these biomolecules, are increasingly utilized in deuterated forms in diverse fields, such as metabolic tracing and neutron scattering studies. In this study, we have developed an efficient deuteration method that targets all 20 proteinogenic amino acids, including their side chains. Using a Pt/C-catalyzed hydrogen–deuterium exchange reaction, the reaction parameters were optimized to achieve the selective and stable incorporation of deuterium. In addition, the resulting deuterated compounds, focusing on tryptophan, were characterized in order to assess their physicochemical properties. Because the deuteration reaction caused significant racemization of amino acids, deuterated D/L-tryptophan was isolated using a chiral separation method. Deuterated tryptophan characterization studies confirmed that the photostability was markedly enhanced by deuteration, whereas the acid stability showed no clear isotopic effect. The X-ray crystal structure analyses revealed minimal changes upon the hydrogen-to-deuterium substitution. These results provide a robust platform for the supply of deuterated amino acids, facilitating their application in drug development, structural analysis, and creation of advanced functional biomaterials.