Synthesis, crystal structure, and molecular conformation of peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH

Abstract

The peptide N-Boc-L-Pro-dehydro-Phe-L-Gly-OH was synthesized by the usual workup procedure and finally coupling the N-Boc-L-Pro-dehydro-Phe to glycine. The peptide crystallizes in monoclinic space group P2₁ with a = 8.951(4) Å, b = 5.677 (6) Å, c = 21.192(11) Å, β = 96.97(4)°, V = 1069(1) ų, Z = 2, d_m = 1.295(5) Mgm⁻³, and d_c = 1.297(4) Mgm⁻³. The structure was determined by direct methods using SHELXS86. The structure was refined by the block-diagonal least-squares procedure to an R value of 0.074 for 1002 observed reflections. The C^α₂-C^β ₂distance of 1.33(2) Å is an appropriate double bond length. The angle C^α-C^β -C^ϒ is 133(1)°. The peptide backbone torsion angles are θ¹ = −167(1)°, ω₀ = 179(1)°, Φ₁ = −48(1)°, ψ₁ = 137(1)°, ω₁ = 175(1)°, Φ₂ = 65(2)°, ψ₂ = 15(2)°, ω₂ = −179(1)°, and Φ₃ = −166(1)°. These values show that the Boc group has a trans-trans conformation while the peptide backbone adopts a β-turn II conformation, which is stablized by an intramolecular hydrogen bond of length of 3.05(1) Å. The structures of dehydro-Phe containing peptides suggest that the dehydro-Phe promotes the β-turn II conformation. The five-membered pyrrolidine ring of the Pro residue adopts an ideal C-exo conformation with torsion angles χ¹₁ = −24(1)°, χ²₁ = 34(1)°, χ³₁ = −30(1)°, χ⁴₁ = 15(1)°, and θ⁰₁ = 6(1)°. The side chain torsion angles in dehydro-Phe are χ¹₂ = −1(2)°, χ^2,1₂ = −176(1)°, andχ^2,2₂ = 8(2)°. The Plane of C^α₂-C^β ₂-C^ϒ₂ is rotated with respect to the plane of the phenyl ring at 7(1)°, which indicates that the atoms of the side chain of dehydro-Phe are essentially coplanar. The molecules form a 2₁ screw axis related hydrogen-bonded rows along the b axis.