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。
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 pro-filing 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.