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

Shibazaki, Chie ; Sugiyama, Haruki ; Ueda, Misaki ; Oku, Takayuki ; Adachi, Motoyasu ; Fisher, Zoë LU and Akutsu-Suyama, Kazuhiro (2025) In Bioengineering 12(9).
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amino acid, crystal, deuteration, isotope effect, optical isomer
in
Bioengineering
volume
12
issue
9
article number
981
publisher
MDPI AG
external identifiers
  • pmid:41007226
  • scopus:105017384883
ISSN
2306-5354
DOI
10.3390/bioengineering12090981
language
English
LU publication?
yes
id
6e9e7ccf-b444-4b0e-812c-2952539c1840
date added to LUP
2025-11-27 12:45:46
date last changed
2025-12-11 14:14:27
@article{6e9e7ccf-b444-4b0e-812c-2952539c1840,
  abstract     = {{<p>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.</p>}},
  author       = {{Shibazaki, Chie and Sugiyama, Haruki and Ueda, Misaki and Oku, Takayuki and Adachi, Motoyasu and Fisher, Zoë and Akutsu-Suyama, Kazuhiro}},
  issn         = {{2306-5354}},
  keywords     = {{amino acid; crystal; deuteration; isotope effect; optical isomer}},
  language     = {{eng}},
  number       = {{9}},
  publisher    = {{MDPI AG}},
  series       = {{Bioengineering}},
  title        = {{Development of the Direct Deuteration Method for Amino Acids and Characterization of Deuterated Tryptophan}},
  url          = {{http://dx.doi.org/10.3390/bioengineering12090981}},
  doi          = {{10.3390/bioengineering12090981}},
  volume       = {{12}},
  year         = {{2025}},
}