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D-Peptide and D-Protein Technology: Recent Advances,Challenges, and Opportunities**
Authors:Alexander J Lander  Dr Yi Jin  Dr Louis Y P Luk
Affiliation:1. School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT UK;2. Manchester Institute of Biotechnology, The University of Manchester, Manchester, M1 7DN UK
Abstract: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:chemical protein synthesis  chemical ligation  D-proteins  mirror-image proteins  peptides  proteins  protein engineering
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