Design of Peptides With A,B-Dehydro Residues: Synthesis, Crystal Structure and Molecular Conformation of N-Boc-Phe-DPhe-Ile-OCH3
Chemistry and Biochemistry
To develop a complete set of design rules with α,β-dehydro residues, a tripeptide N-Boc-Phe- Phe-Ile-OCH3 was synthesized. The synthesis was carried out in solution phase using azlactone procedure. The three-dimensional structure of the peptide was determined by X-ray diffraction method and refined to an R-factor of 0.085. The structure contains three peptide molecules in the asymmetric unit. In all the three crystallographically independent molecules Phe residue adopts one of the three conformations that have been reported for a Phe residue. The overall conformations of three peptide molecules in the asymmetric unit are not similar. Two out of three crystallographically independent molecules adopt type II β-turn conformations whereas the third molecule is found having the characteristic S-shaped conformation in which the values of dihedral angles φ, ψ have opposite signs alternately. One of these two types of conformations has been observed when a Phe is introduced at (i + 2) position of a tetrapeptide. The β-turn conformation is stabilized by a 4 → 1 hydrogen bond where the hydrophobic side chains of residues at (i + 1) and (i + 3) positions stabilized the unfolded conformation with van der Waals interactions. The three independent molecules are locked together by three hydrogen bonds between molecules A and B and two hydrogen bonds between molecules B and C. KE
(2005). Design of Peptides With A,B-Dehydro Residues: Synthesis, Crystal Structure and Molecular Conformation of N-Boc-Phe-DPhe-Ile-OCH3. Structural Chemistry, 16, 445-452.
Available at: https://aquila.usm.edu/fac_pubs/7537