biostudies-literatureChecco JWNIDA NIH HHSHHS | NIH | National Institute of Neurological Disorders and StrokeHHS | NIH | National Institute on Drug AbuseNational Natural Science Foundation of ChinaNINDS NIH HHSNIH HHS16862-16873https://www.ebi.ac.uk/biostudies/studies/S-EPMC6204918biostudies-literatureUnknown293(43)l- to d-residue isomerization is a post-translational modification (PTM) present in neuropeptides, peptide hormones, and peptide toxins from several animals. In most cases, the d-residue is critical for the biological function of the resulting d-amino acid-containing peptide (DAACP). Here, we provide an example in native neuropeptides in which the DAACP and its all-l-amino acid epimer are both active at their newly identified receptor <i>in vitro</i> and at a neuronal target associated with feeding behavior. On the basis of sequence similarity to a known DAACP from cone snail venom, we hypothesized that allatotropin-related peptide (ATRP), a neuropeptide from the neuroscience model organism <i>Aplysia californica</i>, may form multiple diastereomers in the <i>Aplysia</i> central nervous syThe Journal of biological chemistryAplysia allatotropin-related peptide and its newly identified d-amino acid-containing epimer both activate a receptor and a neuronal target.PMC6204918P40 OD010952R01 NS031609P30 DA01831031671097 and 31371104Checco JWZhang GJing JLe ZWSweedler JVYuan WDfalseAplysia allatotropin-related peptide and its newly identified d-amino acid-containing epimer both activate a receptor and a neuronal target.l- to d-residue isomerization is a post-translational modification (PTM) present in neuropeptides, peptide hormones, and peptide toxins from several animals. In most cases, the d-residue is critical for the biological function of the resulting d-amino acid-containing peptide (DAACP). Here, we provide an example in native neuropeptides in which the DAACP and its all-l-amino acid epimer are both active at their newly identified receptor <i>in vitro</i> and at a neuronal target associated with feeding behavior. On the basis of sequence similarity to a known DAACP from cone snail venom, we hypothesized that allatotropin-related peptide (ATRP), a neuropeptide from the neuroscience model organism <i>Aplysia californica</i>, may form multiple diastereomers in the <i>Aplysia</i> central nervous sy2018-01-01T00:00:00Z2018 Oct2026-04-15T17:04:59.441Z2019-11-05T08:04:18ZS-EPMC62049183019428310.1074/jbc.RA118.00436710.1074/jbc.ra118.004367