D-Peptide and D-Protein Technology: Recent Advances, Challenges, and Opportunities

Chembiochem. 2023 Feb 14;24(4):e202200537. doi: 10.1002/cbic.202200537. Epub 2022 Nov 16.


Total chemical protein synthesis provides access to entire D-protein enantiomers enabling unique applications in molecular biology, structural biology, and bioactive compound discovery. Key enzymes involved in the central dogma of molecular biology have been prepared in their D-enantiomeric forms facilitating the development of mirror-image life. Crystallization of a racemic mixture of L- and D-protein enantiomers provides access to high-resolution X-ray structures of polypeptides. Additionally, D-enantiomers of protein drug targets can be used in mirror-image phage display allowing discovery of non-proteolytic D-peptide ligands as lead candidates. This review discusses the unique applications of D-proteins including the synthetic challenges and opportunities.

Keywords: D-proteins; chemical ligation; chemical protein synthesis; mirror-image proteins; peptides; protein engineering; proteins.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Surface Display Techniques
  • Crystallography, X-Ray
  • Peptides* / chemistry
  • Proteins* / chemistry
  • Stereoisomerism


  • Proteins
  • Peptides