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

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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.