Development of tissue peptidome analysis technology and its application to discovery of new biologically active peptides

生物活性肽（BAPs）是细胞间信号传导的重要调节因子，广泛应用于药物和诊断。因此，细胞或组织中的完整肽（肽组）的数据集是未来药物和诊断开发的有前途的资源。质谱法使我们能够分析许多肽，但蛋白酶仍然阻碍肽组分析，即它们快速降解肽并将蛋白质转化为肽。我们已经成功地分析了完整形式的培养细胞的条件培养基中的肽，但不是在组织中。最近，我们提出了一种新的方法，专门标记降解肽使用小膜渗透试剂，并在这项研究中开发的标记方法。虽然标记率低于预期，但我们可以从鉴定的肽列表中排除降解的肽。这种方法将有助于对内源性肽进行分类和发现新的BAP。

Biologically active peptides (BAPs) are well known as key regulators in the signaling between cells, and used for drugs and diagnosis. Thus, a data set of whole peptides (peptidome) in the cell or tissue is a promising resource for future development of drug and diagnosis. Mass spectrometry has enabled us to analyze numerous peptides, but proteases still hamper the peptidome analysis, i.e. they quickly degraded peptides and converted proteins into peptides. We have succeeded in analyzing peptides in the conditioned media of cultured cells in their intact forms, but not in the tissues. We have recently proposed a new approach to specifically label degraded peptides using a small membrane-permeable reagent, and developed the labeling method in this study. Although the labeling ratio is lower than expected, we can exclude the degraded peptides from the list of identified peptides. This method will facilitate cataloging the endogenous peptides and discovery of new BAPs.