The Use of D-amino Acids in Peptide Design

Proteins and most naturally occurring peptides are composed of amino acids of the L-configuration. Damino acids are found as constituents of natural peptides produced primarily, by microorganisms, using a non-ribosomal mechanism of synthesis. Research in this field dates back to over 60 years ago when Lipmann et al noted the presence of D-amino acids in tyrocidines and gramicidins [1]. Post-translational epimerization is an infrequently used mechanism in higher organisms for the introduction of D-amino acids into polypeptide chains [2]. Some notable examples are the production of opioid peptides, namely dermorphins and deltorphins form the skin of various frog species belonging to the Phyllomedusinae subfamily [3] and the contryphans produced by cone snails via post-translational epimerization [4]. Recently, total chemical synthesis of proteins containing all-D residues has been carried out and the characteristics and enzymatic activity of such enantiomeric proteins has been analyzed [5-7]. The incorporation of Damino acids into polypeptide chains imposes local conformational constraints [8]. The purpose of this review is to examine the use of D-amino acids in the design of peptides adopting well-defined folded conformations.