Peptide Design Using \alpha , \beta - Dehydro Amino Acids: From \beta -Turns to Helical Hairpins

Incorporation of \alpha,\beta -dehydrophenylalanine (\bigtriangleup Phe) residue in peptides induces folded conformations: \beta -turns in short peptides and $3_{10}$ -helices in larger ones. A few exceptions - namely, \alpha -helix or flat \beta -bend ribbon structures - have also been reported in a few cases. The most favorable conformation of \bigtriangleup Phe residues are (\phi,\psi) \sim $(-60^o, -30^o), (-60^o, 150^o), (80^o, 0^o)$ or their enantiomers. \bigtriangleup Phe is an achiral and planar residue. These features have been exploited in designing \bigtriangleup Phe zippers and helix-turn-helix motifs. \bigtriangleup Phe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more \bigtriangleup Phe amino acids induce left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the \bigtriangleup Phe residue play an important role in molecular association. The C-H...O=C hydrogen bond between the \bigtriangleup Phe side-chain and backbone carboxyl moiety, \pi - \pi stacking interactions between \bigtriangleup Phe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a \bigtriangleup Phe ring to form the hub of multicentered interactions namely, a donor in aromatic C-H...\pi and C-H...O=C and an acceptor in a $CH_3...\pi$ interaction suggests its exploitation in introducing long-range interactions in the folding of supersecondary structures