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

✍ Scribed by Puniti Mathur; S. Ramakumar; V. S. Chauhan

• Publisher: Wiley (John Wiley & Sons)
• Year: 2004
• Tongue: English
• Weight: 269 KB
• Volume: 76
• Category: Article
• ISSN: 0006-3525
• DOI: 10.1002/bip.10571

✦ Synopsis

Abstract

Incorporation of α,β‐dehydrophenylalanine (ΔPhe) residue in peptides induces folded conformations: β‐turns in short peptides and 3~10~‐helices in larger ones. A few exceptions—namely, α‐helix or flat β‐bend ribbon structures—have also been reported in a few cases. The most favorable conformation of ΔPhe residues are (ϕ,ψ) ∼ (−60°, −30°), (−60°, 150°), (80°, 0°) or their enantiomers. ΔPhe is an achiral and planar residue. These features have been exploited in designing ΔPhe zippers and helix–turn–helix motifs. ΔPhe can be incorporated in both right and left‐handed helices. In fact, consecutive occurrence of three or more ΔPhe amino acids induce left‐handed screw sense in peptides containing L‐amino acids. Weak interactions involving the ΔPhe residue play an important role in molecular association. The CH···OC hydrogen bond between the ΔPhe side‐chain and backbone carboxyl moiety, π–π stacking interactions between ΔPhe side chains belonging to enantiomeric helices have shown to stabilize folding. The unusual capability of a ΔPhe ring to form the hub of multicentered interactions namely, a donor in aromatic CH···π and CH···OC and an acceptor in a CH~3~···π interaction suggests its exploitation in introducing long‐range interactions in the folding of supersecondary structures. © 2004 Wiley Periodicals, Inc. Biopolymers (Pept Sci), 2004