Design and Study of Peptides Containing 1:1 Left- and Right-Handed Helical Patterns from Aminopyrancarboxylic Acids

(R,R)‐ and (S,S)‐aminopyrancarboxylic acids (APyCs) were used in the design of mixed β‐ and α/β‐peptides in alternation with β‐hGly and L‐Ala/D‐Ala, respectively. The enantiomeric β‐ and α/β‐tetrapeptides were then coupled in a 1:1 fashion to give octapeptides with 12/10‐ and 9/11‐mixed helices, respectively. The structure of the helices, with their characteristic hydrogen‐bonding patterns and an additional stabilizing interaction between peptide‐bond NH groups and pyran‐ring oxygen atoms, was investigated by NMR spectroscopy, molecular dynamics, and quantum chemical studies. The presence of equal parts of left‐ and right‐handed helices was confirmed by the cancellation of their respective CD patterns. Despite the disruption of the hydrogen bonding in the transition region, the helical conformation was maintained in the octamers. This study demonstrates the possibility of accommodating helices of opposite handedness within the same peptide. (R,R)‐APyC and (S,S)‐APyC were used in the design of helical β‐ and α/β‐peptides in 1:1 alternation with β‐hGly and L‐Ala/D‐Ala. Coupling of left‐ and right‐handed helical peptides of this type demonstrates their good compatibility in overall helical structures, despite the change of handedness.