Bioanalytical Reviews

, Volume 1, Issue 1, pp 7–24 | Cite as

Analysis of endogenous d-amino acid-containing peptides in Metazoa

  • Lu Bai
  • Sarah Sheeley
  • Jonathan V. SweedlerEmail author


Peptides are chiral molecules with their structure determined by the composition and configuration of their amino acid building blocks. The naturally occurring amino acids, except glycine, possess two chiral forms. This allows the formation of multiple peptide diastereomers that have the same sequence. Although living organisms use l-amino acids to make proteins, a group of d-amino acid-containing peptides (DAACPs) has been discovered in animals that have at least one of their residues isomerized to the d-form via an enzyme-catalyzed process. In many cases, the biological functions of these peptides are enhanced due to this structural conversion. These DAACPs are different from those known to occur in bacterial cell wall and antibiotic peptides, the latter of which are synthesized in a ribosome-independent manner. DAACPs have now also been identified in a number of distinct groups throughout the Metazoa. Their serendipitous discovery has often resulted from discrepancies observed in bioassays or in chromatographic behavior between natural peptide fractions and peptides synthesized according to a presumed all-l sequence. Because this l to d post-translational modification is subtle and not detectable by most sequence determination approaches, it is reasonable to suspect that many studies have overlooked this change; accordingly, DAACPs may be more prevalent than currently thought. Although diastereomer separation techniques developed with synthetic peptides in recent years have greatly aided in the discovery of natural DAACPs, there is a need for new, more robust methods for naturally complex samples. In this review, a brief history of DAACPs in animals is presented, followed by discussion of a variety of analytical methods that have been used for diastereomeric separation and detection of peptides.


High Performance Liquid Chromatography Collisionally Induce Dissociation Electron Capture Dissociation Chiral Selector Collisionally Activate Dissociation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This material is based upon the work supported by the National Science Foundation under Award No. CHE-04-00768, the National Institutes of Health under Award No. NS031069, and the National Institute of Drug Abuse under Award No. DA018310 to the UIUC Neuroproteomics Center on Cell–Cell Signaling.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Lu Bai
    • 1
    • 3
  • Sarah Sheeley
    • 2
  • Jonathan V. Sweedler
    • 2
    • 3
    Email author
  1. 1.Department of Molecular and Integrative PhysiologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of ChemistryUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  3. 3.Beckman Institute for Advanced Science and TechnologyUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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