Gupta_2011_Biopolymers_95_161

The de novo design of peptides and proteins has emerged as an approach for investigating protein structure and function. The success relies heavily on the ability to design relatively short peptides that can adopt stable secondary structures. To this end, substitution with alpha,beta-dehydroamino acids, especially alpha,beta-didehydrophenylalanine (DeltaPhe or DeltaF) has blossomed in manifold directions, providing a rich diversity of well-defined structural motifs. Introduction of alpha,beta-didehydrophenylalanine induces beta-bends in small and 3(10)-helices in longer peptide sequences. Most favorable conformation of DeltaF residues are (phi,psi) approximately (60 degrees , 30 degrees ), (-60 degrees , -30 degrees ), (-60 degrees , 150 degrees ), and (60 degrees , -150 degrees ). These features have been exploited in designing helix-turn-helix, helical bundle arrangements, and glycine zipper type super secondary structural motifs. The unusual capability of alpha,beta-didehydrophenylalanine ring to form a variety of multicentered interactions (N-H...O, C-H...O, C-H...pi, and N-H...pi) suggests its possible exploitation for future de novo design of supramolecular structures. This work has now been extended to the de novo design of peptides with antibiotic, antifibrillization activity, etc. More recently, self-assembling properties of small dehydropeptides have been explored. This review focuses primarily on the structural and functional behavior of alpha,beta-didehydrophenylalanine containing peptides.