Helix aggregation in peptide crystals: occurrence of either all parallel or antiparallel packing motifs for α-helices in polymorphs of Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe

Abstract

Three crystalline polymorphs of the helical decapeptide, Boc-Aib-Ala-Leu-Ala-Leu-Aib-Leu-Ala-Leu-Aib-OMe, have been obtained. Antiparallel helix aggregation is observed in crystals grown from methanol (A), while completely parallel packing is observed in crystals from isopropanol (B) or an ethylene glycol-ethanol mixture (C). Crystals B and C are very similar in molecular conformation and packing. The packing motifs in crystals A and B consist of rows of parallel molecules, with an almost identical arrangement in both crystals. In crystal A, adjacent rows assemble with helix axes pointed in oppsite directions, whereas in crystal B all rows assemble with helix axes pointed in the same direction. Electrostatic interactions between helix dipoles do not appear to be a major determinant of packing modes. The structures also do not provide a ready rationalization of packing preferences in terms of side-chain interactions or solvation. The -helix of the peptide in crystal A has seven 5→1 hydrogen bonds; the helix in crystal B is a mixed 3₁₀/α-helix. The crystal parameters are as follows. Crystal A: C₅₁H₉₂N₁₀O₁₃.CH₃OH, space group P2₁ with a = 10.498(1) Å, b = 18.189(3) Å, c = 16.475(3) Å, β = 99.28(1)°, Z = 2, R = 9.6% for 1860 data. Crystal B: C₅₁H₉₂N₁₀O₁₃.C₃H₇OH, space group P2₁ with a = 10.534(1) Å, b = 28.571(4) Å, c = 11.055(2) Å, β= 95.74(1)°, Z = 2, R = 6.5% for 3251 data. Crystal C: C₅₁H₉₂N₁₀O₁₃.C₂H₅OH, space group P2₁, with a = 10.450(1) Å, b = 28.442(5) Å, c = 11.020(2) Å, β= 95.44(1)°, Z = 2, R = 14.8% (isotropic) for 1948 data.