TY - JOUR
T1 - High-Precision Sulfur Metabolomics Innovated by a New Specific Probe for Trapping Reactive Sulfur Species
AU - Kasamatsu, Shingo
AU - Ida, Tomoaki
AU - Koga, Taisei
AU - Asada, Kosho
AU - Motohashi, Hozumi
AU - Ihara, Hideshi
AU - Akaike, Takaaki
N1 - Funding Information:
This work was supported, in part, by Grants-in-Aid for Scientific Research to S.K. (19K06537), T.A. (18H05277), and H.I. (16H04674) from the Ministry of Education, Sciences, Sports and Technology (MEXT), Japan; a grant from the Agency for Medical Research and Development (AMED) to H.M. ( JP19gm5010002); and a Grant-in-Aid for Scientific Research on Innovative Areas to T.A. (26111008) from MEXT, Japan. This work was also supported, in part, by a grant from the Smoking Research Foundation to H.I. (2017G036), and a grant from JST, CREST, Japan to T.A. (JPMJCR2024).
Publisher Copyright:
© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.
PY - 2021/6/20
Y1 - 2021/6/20
N2 - Aims: Persulfides and other reactive sulfur species are endogenously produced in large amounts in vivo and participate in multiple cellular functions underlying physiological and pathological conditions. In the current study, we aimed to develop an ideal alkylating agent for use in sulfur metabolomics, particularly targeting persulfides and other reactive sulfur species, with minimal artifactual decomposition. Results: We synthesized a tyrosine-based iodoacetamide derivative, N-iodoacetyl l-Tyrosine methyl ester (TME-IAM), which reacts with the thiol residue of cysteine identically to that of β-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), a commercially available reagent. Our previous study revealed that although various electrophilic alkylating agents readily decomposed polysulfides, HPE-IAM exceptionally stabilized the polysulfides by inhibiting their alkaline hydrolysis. The newly synthesized TME-IAM stabilizes oxidized glutathione tetrasulfide more efficiently than other alkylating agents, including HPE-IAM, iodoacetamide, and monobromobimane. In fact, our quantitative sulfur-related metabolome analysis showed that TME-IAM is a more efficient trapping agent for endogenous persulfides/polysulfides containing a larger number of sulfur atoms in mouse liver and brain tissues compared with HPE-IAM. Innovation and Conclusions: We developed a novel iodoacetamide derivative, which is the most ideal reagent developed to date for detecting endogenous persulfides/polysulfides formed in biological samples, such as cultured cells, tissues, and plasma. This new probe may be useful for investigating the unique chemical properties of reactive persulfides, thereby enabling identification of novel reactive sulfur metabolites that remain unidentified because of their instability, and thus can be applied in high-precision sulfur metabolomics in redox biology and medicine. We did not perform any clinical experiments in this study. Antioxid. Redox Signal. 34, 1407-1419.
AB - Aims: Persulfides and other reactive sulfur species are endogenously produced in large amounts in vivo and participate in multiple cellular functions underlying physiological and pathological conditions. In the current study, we aimed to develop an ideal alkylating agent for use in sulfur metabolomics, particularly targeting persulfides and other reactive sulfur species, with minimal artifactual decomposition. Results: We synthesized a tyrosine-based iodoacetamide derivative, N-iodoacetyl l-Tyrosine methyl ester (TME-IAM), which reacts with the thiol residue of cysteine identically to that of β-(4-hydroxyphenyl)ethyl iodoacetamide (HPE-IAM), a commercially available reagent. Our previous study revealed that although various electrophilic alkylating agents readily decomposed polysulfides, HPE-IAM exceptionally stabilized the polysulfides by inhibiting their alkaline hydrolysis. The newly synthesized TME-IAM stabilizes oxidized glutathione tetrasulfide more efficiently than other alkylating agents, including HPE-IAM, iodoacetamide, and monobromobimane. In fact, our quantitative sulfur-related metabolome analysis showed that TME-IAM is a more efficient trapping agent for endogenous persulfides/polysulfides containing a larger number of sulfur atoms in mouse liver and brain tissues compared with HPE-IAM. Innovation and Conclusions: We developed a novel iodoacetamide derivative, which is the most ideal reagent developed to date for detecting endogenous persulfides/polysulfides formed in biological samples, such as cultured cells, tissues, and plasma. This new probe may be useful for investigating the unique chemical properties of reactive persulfides, thereby enabling identification of novel reactive sulfur metabolites that remain unidentified because of their instability, and thus can be applied in high-precision sulfur metabolomics in redox biology and medicine. We did not perform any clinical experiments in this study. Antioxid. Redox Signal. 34, 1407-1419.
KW - alkylating agent
KW - persulfide
KW - redox biology
KW - sulfur omics
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UR - http://www.scopus.com/inward/citedby.url?scp=85107619528&partnerID=8YFLogxK
U2 - 10.1089/ars.2020.8073
DO - 10.1089/ars.2020.8073
M3 - Article
C2 - 33198504
AN - SCOPUS:85107619528
SN - 1523-0864
VL - 34
SP - 1407
EP - 1419
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 18
ER -