Detecting single amino acids and small peptides by combining isobaric tags and peptidomics

Single amino acids and small endogenous peptides play important roles in maintaining a properly functioning organism. These molecules are however currently only routinely identified in targeted approaches. In a small proof-of-concept mass spectrometry experiment we found that by combining isobaric tags and peptidomics, and by targeting singly charged molecules, we were able to identify a significant amount of single amino acids and small endogenous peptides using a basic mass-based identification approach. While there is still room for improvement, our simple test indicates that a limited amount of extra work when setting up the mass spectrometry experiment could potentially lead to a wealth of additional information.