Synthesis and conformational studies of a hybrid β-alanine-morpholine tetramer

A new morpholine-containing foldameric hybrid peptide was synthesized in solution phase, and the conformational preferences were assessed by means of NMR and molecular modeling calculations. All data suggested the existence of two equilibrating conformations involving hydrogen-bonds in the major rotamer. Moreover, calculations on higher model foldamers indicated seven-membered ring hydrogen-bond forming γ-turns as the main driving force in the stabilization of helix-folded conformations. Thus, this study suggests the possibility of using morpholine-3-COOH as a proline surrogate to generate higher α/β hybrid peptides.

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