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

IF 6.7 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Analytical Chemistry Pub Date : 2024-12-03 Epub Date: 2024-11-18 DOI:10.1021/acs.analchem.4c03145
Qinwen Xiao, Meiyu Gao, Jiarui Sun, Yuan Tian, Zunjian Zhang, Pei Zhang, Fengguo Xu
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引用次数: 0

摘要

酰化氨基酸(acyl-AAs)由氨基酸头和有机酸尾组成,在各种生物过程中发挥着重要作用。甘氨酸(Gly)是最常见的酰化底物,其有机酸尾部具有相当大的多样性。丙氨酸(Ala)也存在多种酰化形式,主要由长链脂肪酸修饰。然而,酰化甘氨酸和丙氨酸的全部范围在很大程度上仍未得到探索。在这项研究中,我们采用了一种知识驱动的预测方法,将五种不同类别的 111 种有机酸作为潜在的酰基供体,从而生成了 222 种酰基化的甘氨酸和丙氨酸,从而扩大了酰基化甘氨酸和丙氨酸的范围。为了提高质谱(MS)响应,我们采用了基于化学衍生的 LC-MS/MS 方法,使用二甲基氨基萘-1-磺酰基哌嗪(Dns-PP)及其稳定同位素标记形式(d6-Dns-PP)作为标记试剂。此外,还利用源内片段化(ISF)增加了片段的多样性和实用性,有助于结构的阐明。通过这一策略,在大鼠生物基质中鉴定出了 53 种酰化甘氨酸和阿拉代谢物,其中包括 17 种具有不同组织特异性分布的新型代谢物。我们的方法加深了对酰化 Gly 和 Ala 的生理和病理作用的理解,同时也为发现其他修饰代谢物开辟了途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Discovery of Acylated Glycine and Alanine by Integrating Chemical Derivatization-Based LC-MS/MS and Knowledge-Driven Prediction.

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.

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来源期刊
Analytical Chemistry
Analytical Chemistry 化学-分析化学
CiteScore
12.10
自引率
12.20%
发文量
1949
审稿时长
1.4 months
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.
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