Mass spectrometry in the discovery of peptides involved in intercellular communication: From targeted to untargeted peptidomics approaches

Endogenous peptide hormones/cytokines represent an essential class of biomolecules, which regulate cell–cell communications in diverse physiological processes of organisms. Mass spectrometry (MS) has been developed to be a powerful technology for identifying and quantifying peptides in a highly efficient manner. However, it is difficult to directly identify these peptide hormones/cytokines due to their diverse characteristics, dynamic regulations, low abundance, and existence in a complicated biological matrix. In this work, we summarized and discussed the roles of targeted and untargeted MS in discovering peptide hormones/cytokines using bioassay‐guided purification, bioinformatics screening, or the peptidomics‐based approach. Although the MS-based untargeted comparative peptidomics approach is expected to discover novel peptide hormones/cytokines unbiasedly, only a limited number of successful cases have been reported. The first successful example of discovering a novel peptide hormone (CAPE family) in plants using an untargeted comparative peptidomics approach was published by our team. We discussed the critical challenges and corresponding measures for the peptidomics approach from the steps of sample preparation, peptide extraction, and separation to the MS data acquisition and analysis. By identifying current and emerging technologies and methods that can be integrated into the discovery platform, we proposed an approach and direction for more comprehensive discovery and studying of the roles of the peptide hormones/cytokines operating in diverse organisms.


Co-researchers:Kai-Ting Fan, Chia-Wei Hsu