| Summary: | Bioactive peptides are present in all metazoan species where they orchestrate diverse functions. In the last decade, high-throughput approaches based on mass spectrometry helped the identification of endogenously occurring peptides in different species. We here review biochemical strategies to obtain sequence information of natural (non-tryptic) peptides in Caenorhabditis elegans and in the related nematodes Caenorhabditis briggsae and Ascaris suum with particular attention for sample preparation and methodology. In addition, we describe seven new C. elegans neuropeptides that we recently discovered by sequencing additional peptides. Finally, we explain how differential peptidomics approaches were used to characterize key neuropeptide processing enzymes.
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