Control of peptide conformation by the Thorpe-Ingold effect (C-alpha-tetrasubstitution)

The preferred conformations of peptides heavily based on the currently extensively exploited achiral and chiral alpha-amino acids with a quaternary alpha-carbon atom, as determined by conformational energy computations, crystal-state (X-ray diffraction) analyses, and solution (NMR and spectroscopic) investigations, are reviewed. It is concluded that 3(10)/alpha-helical structures and the fully-extended (C-5) conformation are preferentially adopted by peptide sequences characterized by this family of amino acids, depending upon overall bulkiness and nature (e.g., whether acyclic or C-alpha - C-alpha cyclized) of their side chains.