Oral Presentation 10th Australian Peptide Conference 2013

Total Chemical Synthesis of Mirror Image Proteins (#19)

Stephen Kent 1
  1. Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, USA

All natural protein molecules are made up of L-amino acids and the achiral amino acid glycine.1  The homochirality of natural proteins molecules is one of the most fundamental aspects of the biosphere. I will present case studies to illustrate the preparation by total chemical synthesis of unnatural ‘mirror image’ D-protein molecules made up of D-amino acids.2  Novel features of these examples include facilitated determination of protein X-ray structures by racemic crystallography,3 and the systematic development of a D-protein antagonist for VEGF-A.4

  1. ‘Introduction to Stereochemistry’ by Kurt Mislow, Dover Publications, New York, 2002
  2. Total chemical synthesis of proteins. Stephen B.H. Kent, Chemical Society Reviews, 38, 338-51 (2009)
  3. Racemic protein crystallography. Todd O. Yeates, Stephen B.H. Kent, Ann. Review Biophysics, 41, 41–61 (2012)
  4. Chemical synthesis and X-ray structure of a heterochiral {D-protein antagonist plus VEGF-A} protein complex by racemic crystallography. Kalyaneswar Mandal, Maruti Uppalapati, Dana Ault-Riché, John Kenney, Joshua Lowitz, Sachdev Sidhu, Stephen B.H. Kent, Proc Natl Acad Sci USA, 109, 14779-14784 (2012)