The fully-extended conformation in peptides and proteins

The intramolecularly H-bonded, fully-extended conformation (C5) of an alpha-amino acid residue [and the resulting 2.0(5)-helix obtained via its propagation] is one of the least extensively investigated types of peptide and protein backbone secondary structure. This situation does still currently occur despite its unique ability to enjoy by far the largest separation per residue among peptide conformations. In this article, we offer a detailed update of our present knowledge on this intriguing 3D-structure of peptides in the crystal state as obtained from recently published investigations, complemented by a statistical analysis for its occurrence in the crystal structures of ?-amino acid derivatives and peptides available in the Cambridge Structural Database. We have expanded this useful information to the results of a bioinformatics analysis performed on this (so far largely unappreciated) conformation authenticated in all proteins solved by X-ray diffraction to a resolution of 1.5 Å. In the last section, we describe the results of our DFT calculations on the conformational preferences of a set of homo-peptides (from monomer to octamer) based on as many as six protein and two non-coded, carefully selected, alpha-amino acids. From this literature survey integrated by new energy calculations we have definitely provided strong support to the thesis that this polypeptide 3D-structure does indeed exist, it should be not neglected in future studies by structural biochemists, and it represents a very attractive, novel backbone for applications for organic, medicinal, and biomaterials chemists.