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Facile and easily popularized synthesis of l-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides

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Abstract

Protein glycosylation is one of the most important post-translational modifications. Also, efficient enrichment and separation of glycopeptides from complex samples are crucial for the thorough analysis of glycosylation. Developing novel hydrophilic materials with facile and easily popularized synthesis is an urgent need in large-scale glycoproteomics research. Herein, for the first time, a one-step functionalization strategy based on metal-organic coordination was proposed and Fe3O4 nanoparticles were directly functionalized with zwitterionic hydrophilic l-cysteine (L-Cys), greatly simplifying the synthetic procedure. The easily synthesized Fe3O4/L-Cys possessed excellent hydrophilicity and brief composition, contributing to affinity for glycopeptides and reduction in nonspecific interaction. Thus, Fe3O4/L-Cys nanoparticles showed outstanding sensitivity (25 amol/μL), high selectivity (mixture of bovine serum albumin and horseradish peroxidase tryptic digests at a mass ratio of 100:1), good reusability (five repeated times), and stability (room temperature storage of 1 month). Encouragingly, in the glycosylation analysis of human serum, a total of 376 glycopeptides with 393 N-glycosylation sites corresponding to 118 glycoproteins were identified after enrichment with Fe3O4/L-Cys, which was superior to ever reported L-Cys modified magnetic materials. Furthermore, applying the one-step functionalization strategy, cysteamine and glutathione respectively direct-functionalized Fe3O4 nanoparticles were successfully synthesized and also achieved efficient glycopeptide enrichment in human serum. The results indicated that we have presented an efficient and easily popularized strategy in glycoproteomics as well as in the synthesis of novel materials.

Fe3O4/L-Cys nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides.

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Acknowledgements

This work was supported by China State Key Research Grant (Project 2016YFA0501402) and National High-Tech R&D Program of China (Project 2012AA020202).

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Authors and Affiliations

  1. Department of Chemistry, Fudan University, Shanghai, 200433, China

    Xiaoyan Feng, Chunhui Deng, Mingxia Gao & Xiangmin Zhang

  2. Institutes of Biomedical Sciences, Fudan University, Shanghai, 200433, China

    Chunhui Deng, Mingxia Gao & Xiangmin Zhang

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  1. Xiaoyan Feng
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  2. Chunhui Deng
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  3. Mingxia Gao
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  4. Xiangmin Zhang
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Correspondence to Xiangmin Zhang.

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The authors declare that they have no conflict of interest. The research followed the tenets of the Declaration of Helsinki, and the use of the human serum samples for research was approved by the Ethics Committee of Zhongshan Hospital, Fudan University. Informed consent was obtained from all individual participants included in the research.

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Published in the topical collection celebrating ABCs 16th Anniversary.

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Feng, X., Deng, C., Gao, M. et al. Facile and easily popularized synthesis of l-cysteine-functionalized magnetic nanoparticles based on one-step functionalization for highly efficient enrichment of glycopeptides. Anal Bioanal Chem 410, 989–998 (2018). https://doi.org/10.1007/s00216-017-0602-5

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