Synthesis and Secondary Structure of Alternate alpha,beta-Hybrid Peptides Containing Oxazolidin-2-one Moieties

The synthesis and conformational analysis of a novel class of foldamers containing (S)-β3-homophenylglycine [(S)-β3- hPhg] and D-4-carboxy-oxazolidin-2-one (D-Oxd) residues in alternate order is reported. The experimental conformational analysis performed in solution by IR, 1H NMR, and CD spectroscopy unambiguously proved that these oligomers fold into ordered structures with increasing sequence length. Theoretical calculations employing ab initio MO theory suggest a helix with 11-membered hydrogen-bonded rings as the preferred secondary structure type. The few formal helix alternatives can be excluded in particular by steric effects of the oxazolidin-2-one rings. The novel structures enrich the field of peptidic foldamers and might be useful in the mimicry of native peptides.