Peptide design using α,β-dehydro amino acids:: From β-turns to helical hairpins

Incorporation of alpha, beta-dehydrophenylalanine (DeltaPhe) residue in peptides induces folded confornzations: beta-turns in short peptieles and 3(10)-helices in larger ones. A few exceptions-namely, a-helix or flat beta-bend ribbon structures-have also been reported in a few cases. The most favorable conformation of DeltaPhe residues are (phi,psi), (-60degrees, 150degrees), (80degrees, 150degrees) or their enantiomers. DeltaPhe is an achiral and planar residue. These features have been exploited in designing APhe zippers and helix-turn-helix motif. APhe can be incorporated in both right and left-handed helices. In fact, consecutive occurrence of three or more DeltaPhe amino acids induce Left-handed screw sense in peptides containing L-amino acids. Weak interactions involving the DeltaPhe residue play an important role in molecular association. The C-H-... O=C hydrogen bond between the DeltaPhe side-chain and backbone carboxyl moiety, pi-pi stacking interactions between DeltaPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a DeltaPhe ring to form the hub of muilticentered interactions namely, a donor in aromatic C-H(...)pi and C-(HO)-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. (C) 2004 Wiley Periodicals, Inc.