Structural Dimorphism Of Achiral Alpha,Gamma-Hybrid Peptide Foldamers: Coexistence Of 12-And 15/17-Helices

Here, novel 12-helices in ,-hybrid peptides composed of achiral -aminoisobutyric acid (Aib) and 4-aminoisocaproic acid (Aic, doubly homologated Aib) monomers in 1:1 alternation are reported. The 12-helices were indicated by solution and crystal structural analyses of tetra- and heptapeptides. Surprisingly, single crystals of the longer nonapeptide displayed two different helix types: the novel 12-helix and an unprecedented 15/17-helix. Quantum chemical calculations on both helix types in a series of continuously lengthened Aib/Aic-hybrid peptides confirm that the 12-helix is more stable than the 15/17-helix in shorter peptides, whereas the 15/17-helix is more stable in longer sequences. Thus, the coexistence of both helix types can be expected within a definite range of sequence lengths. The novel 15/17- and 12-helices in ,-hybrid peptides with 51 and 41 hydrogen-bonding patterns, respectively, can be viewed as backbone-expanded analogues of native - and 3(10)-helices.