Apolar peptide models for conformational heterogeneity, hydration, and packing of polypeptide helices: crystal structure of hepta- and octapeptides containing α-aminoisobutyric acid

Abstract

The crystal structures of two helical peptides Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe (VALU-7) and Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Aib-OMe (VALU-8) have been determined to a resolution of 1.0 and 0.9 Å, respectively. Both the seven and eight residue peptides crystallize with two conformers per asymmetric unit. The VALU-8 conformers are completely helical and differ only at the C-terminus by a sign reversal of the φ ψ angles of the last residue. One of the VALUE-7 conformers occurs as a normal -helix, whereas in the other, the N(7) = O(3) α-type hydrogen bond is ruptured by the entry of a water molecule (W) into the helix, which in turn makes hydrogen bonds N(7)W = 2.97 Å and O(3) = 2.77 Å. The other side of the water molecule is surrounded by a hydrophobic pocket. These two conformers give a static representation of a step in a possible helix unwinding or folding process. In the value-8 crystal the helices aggregate in a parallel mode, whereas the aggregation is antiparallel in the VALUE-7 crystal. The crystal parameters are VALUE-7 crystal. The crystal parameters are VALUE-7, P2₁, a = 10.203 (3) Å, b = 19.744 (6) Å, c = 22.561 (6) Å, α = 96.76°, Z = 4, C₃₈, H₆₉N₇O₁₀·0.5 H₂O, R = 6.65% for 3674 reflections observed gt; 3σ(F): and VALU-8, P2₁, a; = 10.596 (4) Å, b = 27.57 (6) Å, c = 17.745 (5) Å, β = 95.76 (3)°, Z = 4, C₄₂H₇₆N₇₆O₁₁·0.25 CH₃OH, R = 6.63% for 4701 reflections observed gt; 3σ(F).