Design of a peptide hairpin containing a central three-residue loop.
The construction of a designed beta-hairpin structure, containing a central three-residue loop has been successfully achieved in the synthetic nonapeptide Boc-Leu-Phe-Val-(D)Pro-(L)Pro-(D)Ala-Leu-Phe-Val-OMe (2). The design is based on expanding the two-residue loop established in the peptide beta-hairpin Boc-Leu-Phe-Val-(D)Pro-(L)Pro-Leu-Phe-Val-OMe (1). Characterization of the registered beta-hairpins in peptides 1 and 2 is based on the observation of key nuclear Overhauser effects (NOEs) in CDCl(3) and CD(3)OH. Solvent titration and temperature dependence of NH chemical shifts establish the identity of NH groups involved in interstrand hydrogen bonding. In peptide 2, the antiparallel registry is maintained, with the formation of a (D)Pro-(L)Pro-(D)Ala loop, stabilized by a 5-->1 hydrogen bond between Val3 CO and Leu7 NH groups (C(13), alpha-turn) and a 3-->1 hydrogen bond between (D)Pro4 CO and (d)Ala6 NH groups (C(7), gamma-turn). NMR derived structures suggest that in peptide 2, (d)Ala(6) adopts an alpha(L) conformation. In peptide 1, the (D)Pro-(L)Pro segment adopts a type II' beta-turn. Replacement of (D)Ala (6) in peptide 2 by (L)Ala in peptide 3 yields a beta-hairpin conformation, with a central (D)Pro-(L)Pro two-residue loop. Strand slippage at the C-terminus results in altered registry of the antiparallel strands.
Rai
Rajkishor
R
Molecular Biophysics Unit and NMR Research Center, Indian Institute of Science, Bangalore.
Raghothama
Srinivasarao
S
Balaram
Padmanabhan
P
D006860:Hydrogen Bonding; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
D009842:Oligopeptides