Solution conformations of oligomers of alpha-aminoisobutyric acid

The N-acetyl(Aib)nN'-methylamides (with n = 1, 2 and 3) and the N-acetyl-(Aib)3 methyl ester have been synthesized using an oxazolone procedure. An experimental conformational analysis of this series of oligomers has been carried out in water, DMSO-d6 and CDCl3 using n.m.r. techniques, and in chloroform using i.r. spectroscopy. Deuterium exchange rates of amide protons in DMSO-d6 and the rates of these proton chemical shifts with temperature in water, DMSO-d6 and CDCl3 indicate that the oligomeric N'-methylamides adopt conformations that have no hydrogen bonds when n = 1, one hydrogen bond when n = 2, and two hydrogen bonds when n = 3, and that Ac(Aib)3OMe has a conformation with one hydrogen bond. An analysis of the N-H stretching region of the i.r. spectra of these compounds in CHCl3 also suggests the existence of these conformational states. These data imply that the peptides adopt the 3(10)-helical and not the alpha-helical conformation in solution. This conclusion supports the hypothesis that the Aib residue has asymmetric geometry at the C alpha atom in solution, similar to that reported in the literature for the crystalline state.