The first non-helical Aib-containing hexapeptide: The crystal structure of Z-Gly-Aib-Gly-Aib-Gly-Aib-OtBu

The synthetic peptide Z-Gly-Aib-Gly-Aib-Gly-Aib-OtBu was crystallized from a mixture of ethyl acetate and n-hexane. The crystals belong to the centrosymmetric space group Pbca. There are three molecules in the asymmetric unit. The three molecules differ mainly in the Z-group conformation. The first Gly residue adopts a fully extended conformation, residues 2 and 3 lie in the left-handed helical region, residues 4 and 5 in the right-handed helical region, and residue 6 again in the left-handed helical region of the Ramachandran plot. There are only two of four possible intramolecular hydrogen bonds formed, namely, between Aib4 and Gly1 forming a β-turn of type III' and between Aib6 and Gly3 forming a β-turn of type I. The inverted molecules (by space group symmetry) lie in the regions with opposite handedness and form β-turns of type III and I'. In contrast to all known long synthetic and naturally occurring Aib-containing peptides that fold as 3₁₀ - or α-helix, Z-(Gly-Aib)₃ -OtBu folds in a quite flat structure from which only the protecting groups bulge out.