Discovery of Cysteine Carboxyalkylations by Real-Time Isotopic Signature Targeted Profiling

Data-dependent acquisition (DDA) is widely applied in shotgun proteomics. However, restricted by the scanning speed of mass spectrometry (MS) instruments, it remains challenging for DDA to directly detect peptides with low abundance. Herein, we developed a real-time targeted MS data acquisition method, "isoSTAR", which identifies target peptides by their unique isotopic signatures during the stage of full-MS scanning and subjects them to targeted MS/MS scans immediately. The method showed dramatic improvement in sensitivity in identifying target peptides with low abundance compared to traditional MS acquisition methods. Using this method, we discovered a series of carboxyalkylations on cysteines during fatty acid metabolism and verified their modification structures using synthetic peptide standards. We envision that isoSTAR will become a powerful and versatile tool to enhance shotgun proteomics applications in profiling protein-centric modifications.

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Publication Details

Journal
Journal of the American Chemical Society
Published
2025-02-21
DOI
https://doi.org/10.1021/jacs.4c16183
Citations
5
Primary Topic
Advanced Proteomics Techniques and Applications
Type
article
Field-Weighted Citation Impact
3.78

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article

Discovery of Cysteine Carboxyalkylations by Real-Time Isotopic Signature Targeted Profiling

Huan Tang, Yicheng Liu, Guogeng Jia, Zhenchen Tang et al.
5 citations
Journal of the American Chemical Society
Advanced Proteomics Techniques and Applications
3.78
article

Discovery of Cysteine Carboxyalkylations by Real-Time Isotopic Signature Targeted Profiling

Huan Tang, Yicheng Liu, Guogeng Jia, Zhenchen Tang, Fan Yang, Zixuan Zhang, Jinjun Gao, Weidi Xiao, Ying Chen, Chu Wang, Feng Tianyu
article en
5 citations

Abstract

Data-dependent acquisition (DDA) is widely applied in shotgun proteomics. However, restricted by the scanning speed of mass spectrometry (MS) instruments, it remains challenging for DDA to directly detect peptides with low abundance. Herein, we developed a real-time targeted MS data acquisition method, "isoSTAR", which identifies target peptides by their unique isotopic signatures during the stage of full-MS scanning and subjects them to targeted MS/MS scans immediately. The method showed dramatic improvement in sensitivity in identifying target peptides with low abundance compared to traditional MS acquisition methods. Using this method, we discovered a series of carboxyalkylations on cysteines during fatty acid metabolism and verified their modification structures using synthetic peptide standards. We envision that isoSTAR will become a powerful and versatile tool to enhance shotgun proteomics applications in profiling protein-centric modifications.

Journal of the American Chemical SocietyVol. 147(9)
Ministry of Education of the People's Republic of China (CN), Peking University (CN), Beijing National Laboratory for Molecular Sciences (CN), Center for Life Sciences (CN)
National Natural Science Foundation of China, Ministry of Science and Technology of the People's Republic of China
Openalex Percentile: Top 7%
Advanced Proteomics Techniques and Applications
3.78
DOISourceOpenAlex
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