Synthesis and secondary structure of alternate α,β-hybrid peptides containing oxazolidin-2-one moieties

The synthesis and conformational analysis of a novel class of foldamers containing (S)-beta(3)-homophenylglycine [(S)-beta(3)-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, H-1 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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheini Germany, 2007).