{"title":"通过整合基于化学衍生的 LC-MS/MS 和知识驱动的预测发现酰化甘氨酸和丙氨酸","authors":"Qinwen Xiao, Meiyu Gao, Jiarui Sun, Yuan Tian, Zunjian Zhang, Pei Zhang, Fengguo Xu","doi":"10.1021/acs.analchem.4c03145","DOIUrl":null,"url":null,"abstract":"<p><p>Acylated amino acids (acyl-AAs), which consist of an amino acid head and an organic acid tail, play vital roles in various biological processes. Glycine (Gly) is the most common substrate for acylation with the organic acid tails exhibiting considerable diversity. Alanine (Ala) also exists in multiple acylated forms, predominantly modified by long-chain fatty acids. However, the full scope of acylated Gly and Ala remains largely unexplored. In this study, we employed a knowledge-driven prediction approach to expand the spectrum of acylated Gly and Ala by incorporating 111 organic acids from five different classes as potential acyl donors, leading to the generation of 222 acylated Gly and Ala species. To enhance mass spectrometry (MS) response, we used a chemical derivatization-based LC-MS/MS approach, employing dimethylamino-naphthalene-1-sulfonyl piperazine (Dns-PP) and its stable isotope-labeled form (<i>d</i><sub>6</sub>-Dns-PP) as labeling reagents. Moreover, in-source fragmentation (ISF) was utilized to increase the fragment diversity and utility, aiding in structure elucidation. This strategy resulted in the identification of 53 acylated Gly and Ala metabolites in rat biological matrices, including 17 novel metabolites with distinct tissue-specific distributions. Our approach offers a deeper understanding of the physiological and pathological roles of acylated Gly and Ala, while also opening avenues for the discovery of other modified metabolites.</p>","PeriodicalId":27,"journal":{"name":"Analytical Chemistry","volume":" ","pages":"18957-18966"},"PeriodicalIF":6.7000,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Discovery of Acylated Glycine and Alanine by Integrating Chemical Derivatization-Based LC-MS/MS and Knowledge-Driven Prediction.\",\"authors\":\"Qinwen Xiao, Meiyu Gao, Jiarui Sun, Yuan Tian, Zunjian Zhang, Pei Zhang, Fengguo Xu\",\"doi\":\"10.1021/acs.analchem.4c03145\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Acylated amino acids (acyl-AAs), which consist of an amino acid head and an organic acid tail, play vital roles in various biological processes. Glycine (Gly) is the most common substrate for acylation with the organic acid tails exhibiting considerable diversity. Alanine (Ala) also exists in multiple acylated forms, predominantly modified by long-chain fatty acids. However, the full scope of acylated Gly and Ala remains largely unexplored. In this study, we employed a knowledge-driven prediction approach to expand the spectrum of acylated Gly and Ala by incorporating 111 organic acids from five different classes as potential acyl donors, leading to the generation of 222 acylated Gly and Ala species. To enhance mass spectrometry (MS) response, we used a chemical derivatization-based LC-MS/MS approach, employing dimethylamino-naphthalene-1-sulfonyl piperazine (Dns-PP) and its stable isotope-labeled form (<i>d</i><sub>6</sub>-Dns-PP) as labeling reagents. Moreover, in-source fragmentation (ISF) was utilized to increase the fragment diversity and utility, aiding in structure elucidation. This strategy resulted in the identification of 53 acylated Gly and Ala metabolites in rat biological matrices, including 17 novel metabolites with distinct tissue-specific distributions. Our approach offers a deeper understanding of the physiological and pathological roles of acylated Gly and Ala, while also opening avenues for the discovery of other modified metabolites.</p>\",\"PeriodicalId\":27,\"journal\":{\"name\":\"Analytical Chemistry\",\"volume\":\" \",\"pages\":\"18957-18966\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2024-12-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Analytical Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.analchem.4c03145\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.analchem.4c03145","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
Discovery of Acylated Glycine and Alanine by Integrating Chemical Derivatization-Based LC-MS/MS and Knowledge-Driven Prediction.
Acylated amino acids (acyl-AAs), which consist of an amino acid head and an organic acid tail, play vital roles in various biological processes. Glycine (Gly) is the most common substrate for acylation with the organic acid tails exhibiting considerable diversity. Alanine (Ala) also exists in multiple acylated forms, predominantly modified by long-chain fatty acids. However, the full scope of acylated Gly and Ala remains largely unexplored. In this study, we employed a knowledge-driven prediction approach to expand the spectrum of acylated Gly and Ala by incorporating 111 organic acids from five different classes as potential acyl donors, leading to the generation of 222 acylated Gly and Ala species. To enhance mass spectrometry (MS) response, we used a chemical derivatization-based LC-MS/MS approach, employing dimethylamino-naphthalene-1-sulfonyl piperazine (Dns-PP) and its stable isotope-labeled form (d6-Dns-PP) as labeling reagents. Moreover, in-source fragmentation (ISF) was utilized to increase the fragment diversity and utility, aiding in structure elucidation. This strategy resulted in the identification of 53 acylated Gly and Ala metabolites in rat biological matrices, including 17 novel metabolites with distinct tissue-specific distributions. Our approach offers a deeper understanding of the physiological and pathological roles of acylated Gly and Ala, while also opening avenues for the discovery of other modified metabolites.
期刊介绍:
Analytical Chemistry, a peer-reviewed research journal, focuses on disseminating new and original knowledge across all branches of analytical chemistry. Fundamental articles may explore general principles of chemical measurement science and need not directly address existing or potential analytical methodology. They can be entirely theoretical or report experimental results. Contributions may cover various phases of analytical operations, including sampling, bioanalysis, electrochemistry, mass spectrometry, microscale and nanoscale systems, environmental analysis, separations, spectroscopy, chemical reactions and selectivity, instrumentation, imaging, surface analysis, and data processing. Papers discussing known analytical methods should present a significant, original application of the method, a notable improvement, or results on an important analyte.