Design of peptides: crystal and molecular structure of a 3₁₀-helical peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-Och₃

Abstract

Highly specific peptide structures can be designed by inserting dehydro residues into peptide sequences. The peptide N-Boc-L-Phe-dehydro-Phe-L-Val-L-Phe-dehydro-Phe-L-Val-OCH₃, synthesized by conventional procedures, crystallizes from methanol--water mixtures at 4°C in the tetragonal space group P4₃ with cell parameters a = b = 13.829 ± 0.003 Å, c = 27.587 ± 0.008 Å, V = 5275.5 ± 0.2 ų, Z = 4, d_m = 1.152 ± 0.005 g cm^-3, d_cal = 1.150 ± 0.005 g cm^-3. The overall residual factor R = 0.084 for 2342 reflections, with 2θ_max = 140° using CuKα radiation. The backbone torsion angles are θ¹ = -171(1)°, ω₀ = 168 (1)°, Φ₁ = 77 (2)°, Ψ₁ = 41 (2)°, ω_l = 169 (1)°, Φ₂ = -46 (2)°, Ψ₂ = -24 (2)°, ω₂ = 179 (1)°, Φ₃ = -63 (2)°, Φ₃ = -19 (2)°, ω₃ = 171 (1)°, Φ₄ = -67 (2)°, Ψ₄ = -8 (1)°, ω₄ = 169 (1)°, Ψ₅ = -61 (1)°, Φ₅ = -26(1)°, ω ₅ = 177(1)°, Ψ₆ = -122 (1)°, Φ ₆^T = 26 (2)°. The peptide adopts a 3₁₀-helical conformation with three intramolecular hydrogen bonds (i + 3 → i) involving carbonyl oxygen atoms of Phe1, dehydro-Phe2, Val3, and the NH groups of Phe4, dehydro-Phe5, and Val6 with distances of 3.01 (1), 2.82 (1), and 3.09 (2) Å, respectively. The structure determination revealed that a hexapeptide with two dehydro-Phe residues at (i + 2) and (i + 5) positions generates a 3₁₀-helical conformation. The helical peptide molecules are arranged in a major helical arrangement about the 4₃axis. These helices are packed parallel to the c axis and form several interdigitating hydrogen bonds. The interhelix hydrogen-bonding regions are separated by van der Waals interactions involving the side chains of Phe, dehydro-Phe, and Val residues.