Endogenous peptide hormones 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 due to their diverse characteristics, dynamic regulations, low abundance, and existence in a complicated biological matrix. Here, we summarize and discuss the roles of targeted and untargeted MS in discovering peptide hormones using bioassay-guided purification, bioinformatics screening, or the peptidomics-based approach. Although the peptidomics approach is expected to discover novel peptide hormones unbiasedly, only a limited number of successful cases have been reported. The critical challenges and corresponding measures for peptidomics from the steps of sample preparation, peptide extraction, and separation to the MS data acquisition and analysis are also discussed. We also identify emerging technologies and methods that can be integrated into the discovery platform toward the comprehensive study of endogenous peptide hormones.

中文翻译：

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质谱法发现参与细胞间通讯的肽：从靶向肽组学方法到非靶向肽组学方法

内源性肽激素代表了一类重要的生物分子，它调节生物体不同生理过程中的细胞间通讯。质谱 (MS) 已发展成为一种高效识别和定量肽的强大技术。然而，由于这些肽类激素特性多样、动态调控、丰度低且存在于复杂的生物基质中，直接识别它们很困难。在这里，我们总结并讨论了靶向和非靶向 MS 在使用生物测定引导的纯化、生物信息学筛选或基于肽组学的方法发现肽激素中的作用。尽管肽组学方法有望公正地发现新型肽激素，但目前仅报道了有限数量的成功案例。还讨论了肽组学从样品制备、肽提取、分离到质谱数据采集和分析的关键挑战和相应措施。我们还确定了可以集成到发现平台中以全面研究内源性肽激素的新兴技术和方法。