色谱 ›› 2016, Vol. 34 ›› Issue (12): 1192-1198.DOI: 10.3724/SP.J.1123.2016.08037

• 专论与综述 • 上一篇    下一篇

血清磷酸化肽的分离富集和质谱定量及其作为潜在肿瘤标志物的评价

翟贵金1,2, 吴魁1, 汪福意1,3   

  1. 1. 中国科学院化学研究所, 中国科学院活体分析化学重点实验室, 北京 100190;
    2. 天津市医学表观遗传学 重点实验室, 天津医科大学生物化学与分子生物学系, 天津 300070;
    3. 中国科学院大学, 北京 100049
  • 收稿日期:2016-08-30 出版日期:2016-12-08 发布日期:2013-04-24
  • 通讯作者: 汪福意,Tel:(010)62529069,E-mail:fuyi.wang@iccas.ac.cn
  • 基金资助:

    国家自然科学基金项目(21135006,21127901,21275148,21575145,21321003);国家重点基础研究发展计划项目(2013CB531805).

Separation, enrichment, mass spectrometric quantification and evaluation of serum phosphopeptides as potential tumor biomarkers

ZHAI Guijin1,2, WU Kui1, WANG Fuyi1,3   

  1. 1. CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China;
    2. Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin 300070, China;
    3. University of Chinese Academy of Sciences, Beijing 100049, China
  • Received:2016-08-30 Online:2016-12-08 Published:2013-04-24
  • Supported by:

    National Natural Science Foundation of China (Nos. 21135006, 21127901, 21275148, 21575145, 21321003); National Program on Key Basic Research Project of China ("973" Program) (No. 2013CB531805).

摘要:

血清中磷酸化肽种类和浓度的变化既能反映人体内蛋白质水解酶活性的变化,又能反映蛋白质翻译后磷酸化的水平,业已成为肿瘤标志物寻找和发现的重要目标。因而,血清中磷酸化肽的鉴定及其定量分析在具有临床应用价值的肿瘤标志物的筛选与发现中起着重要作用。由于血清中的内源性磷酸化肽丰度极低,在质谱分析中的离子化效率不高,且受到来自高丰度非磷酸化肽和蛋白质的信号抑制及干扰,血清中磷酸化肽的质谱定量分析是分析化学研究中的一个巨大挑战。文章对血清磷酸化肽的分离富集、质谱定量分析及其作为肿瘤标志物的筛选和评价等3个方面的研究进展进行总结、评述,并展望该领域的未来研究趋势和应用前景。

关键词: 分离富集, 磷酸化肽, 血清, 质谱定量, 肿瘤标志物, 综述

Abstract:

Serum phosphopeptides has been a vital objective for the discovery of tumor biomarkers as their levels can reflect the changes in the activities of both endo-and exo-proteases, and the level of protein phosphorylation. Comprehensive analysis of serum phosphopeptides may lead to discovery of novel tumor biomarkers for clinical diagnosis. However, the extremely low abundance of serum phosphopeptides as well as high background level of highly abundant non-phosphoproteins/peptides makes the mass spectrometry (MS)-based phosphopeptide profiling a great challenge. In this review, we will summarize and review update advances in the separation, enrichment and MS quantification of phosphopeptides as well as the evaluation of serum phosphopeptides as potential tumor biomarkers. We will also prospect the future tendency and applications of this multi-disciplinary research field.

Key words: mass spectrometric quantification, phosphopeptides, review, separation and enrichment, serum, tumor biomarkers

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