Solvated helical backbones: X-ray diffraction study of Boc-Ala-Leu-Aib-Ala-Leu-Aib-OMe · H₂O

Abstract

A second example of insertion of a water molecule into the helical backbone of an apolar peptide is presented here and compared to a similar occurrence in a longer peptide with the same type of sequence of residues, i.e., Boc-Aib-(Ala-Leu-Aib)₃-OMe. The backbone of the title compound assumes an approximate 3₁₀-helical form with three 4 → 1 hydrogen bonds. In the place of a fourth 4 →1 hydrogen bond, a water molecule is inserted between O(1) and N(4), and acts as a bridge by forming hydrogen bonds N(4) W(1) (2.95 Å) and W(1) O(1) (2.81Å). The water molecule participates in a third hydrogen bond with a neighboring peptide molecule, W(1) O(4) (2.91 Å). The insertion of the water molecule causes the apolar peptide to mimic an amphiphilic helix. Crystals grown from ethyl acetate/petroleum ether (reported here) or from methanol/water solution are in space group P2₁2₁2₁ with a = 12.024(4) Å, b = 15.714(6) Å, c = 21.411(7) Å, Z = 4 and d_calc = 1.124 g/cm³ for C₃₂H₅₈N₆O₉ · H₂O. The overall agreement factor R is 6.3% for 2707 reflections observed with intensities > 3σ(F) and the resolution is 0.90 Å.