D-amino acid-containing peptides (DAACPs) are enigmatic contributors to the animal peptidome. They form as a result of a post-translational modification, where an isomerizing enzyme converts one residue near the C- or N-terminus of a peptide from an L-amino acid to a D-amino acid. Detection of DAACPs is made challenging by the fact that the all-L-amino acid form of a peptide has the same mass as a DAACP, making it invisible to detection by traditional neuropeptidomic techniques, such as a general liquid chromatography-mass spectrometry (LC-MS/MS) experiment. Traditional DAACP discovery occurred through knowledge of a peptide's bioactivity, intensive work that requires deep understanding of a peptide's expression and potential receptors. The question of prevalence of DAACPs - for example, how many DAACPs are in a particular organism's nervous system - requires a non-targeted methodology. We have developed such a methodology by probing the neuropeptidome of the model organism Aplysia californica, where two DAACPs have already been discovered: NdWFamide (Asn-D-Trp-Phe-amidated) [Sheeley et al, 2005, Analyst] and GdFFD (Gly-D-Phe-Phe-Asp) [Bai et al, 2013, JBC].
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