Shibazaki Chie, Sugiyama Haruki, Ueda Misaki, Oku Takayuki, Adachi Motoyasu, Fisher Zoë, Akutsu-Suyama Kazuhiro
J-PARC Center, Japan Atomic Energy Agency (JAEA), 2-4 Shirakata, Tokai, Naka, Ibaraki 319-1195, Japan.
Neutron Industrial Application Promotion Center, Comprehensive Research Organization for Science and Society (CROSS), 162-1 Shirakata, Tokai, Naka, Ibaraki 319-1106, Japan.
Bioengineering (Basel). 2025 Sep 16;12(9):981. doi: 10.3390/bioengineering12090981.
Proteins and peptides are vital biomolecules, and deuterated amino acids are increasingly applied in areas such as drug discovery, metabolic tracing, and neutron scattering studies. In this study, we performed deuteration on all 20 proteinogenic amino acids, including their side chains, and established efficient methods for 13 amino acids. 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.
蛋白质和肽是重要的生物分子，氘代氨基酸在药物发现、代谢追踪和中子散射研究等领域的应用越来越广泛。在本研究中，我们对包括侧链在内的所有20种蛋白质氨基酸进行了氘代，并建立了13种氨基酸的有效方法。使用Pt/C催化的氢-氘交换反应，对反应参数进行了优化，以实现氘的选择性和稳定掺入。此外，对所得的氘代化合物，重点是色氨酸，进行了表征，以评估其物理化学性质。由于氘代反应导致氨基酸发生显著的消旋化，因此使用手性分离方法分离了氘代D/L-色氨酸。氘代色氨酸表征研究证实，氘代显著提高了光稳定性，而酸稳定性没有明显的同位素效应。X射线晶体结构分析表明，氢到氘的取代引起的变化极小。这些结果为氘代氨基酸的供应提供了一个强大的平台，促进了它们在药物开发、结构分析和先进功能生物材料制备中的应用。
