Carboxypeptidase E and the Identification of Novel Neuropeptides as Potential Therapeutic Targets

Research output: Chapter in Book/Report/Conference proceedingChapter

16 Scopus citations


Peptides and small molecules that bind to peptide receptors are important classes of drugs that are used for a wide variety of different applications. The search for novel neuropeptides traditionally involved a time-consuming approach to purify each peptide to homogeneity and determine its amino acid sequence. The discovery in the 1980s of enkephalin convertase/carboxypeptidase E (CPE), and the observation that this enzyme was involved in the production of nearly every known neuropeptide led to the idea for a one-step affinity purification of CPE substrates. This approach was successfully used to isolate hundreds of known neuropeptides in mouse brain, as well as over a dozen novel peptides. Some of the novel peptides found using this approach are among the most abundant peptides present in brain, but had not been previously identified by traditional approaches. Recently, receptors for two of the novel peptides have been identified, confirming their role as neuropeptides that function in cell–cell signaling. Small molecules that bind to one of these receptors have been developed and found to significantly reduce food intake and anxiety-like behavior in an animal model. This review describes the entire project, from discovery of CPE to the novel peptides and their receptors.

Original languageEnglish (US)
Title of host publicationApprentices to Genius
Subtitle of host publicationA tribute to Solomon H. Snyder
EditorsGavril W. Pasternak, Joseph T. Coyle
PublisherAcademic Press Inc.
Number of pages18
ISBN (Print)9780128140871
StatePublished - Jan 1 2018

Publication series

NameAdvances in Pharmacology
ISSN (Print)1054-3589
ISSN (Electronic)1557-8925


  • Carboxypeptidase
  • Enkephalin
  • Neuropeptide
  • Peptidomics
  • proSAAS

ASJC Scopus subject areas

  • Pharmacology


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