LAUSR

The polyproline‐II helix is the most extended naturally occurring helical structure and is widely present in polar, exposed stretches and “unstructured” denatured regions of polypeptides. Can it be hydrophobic? In this study, we address this question using oligomeric peptides formed by a hydrophobic proline analogue, (2S,3aS,7aS)‐octahydroindole‐2‐carboxylic acid (Oic). Previously, we found the molecular principles underlying the structural stability of the polyproline‐II conformation in these oligomers, whereas the hydrophobicity of the peptide constructs remains to be examined. Therefore, we investigated the octan‐1‐ol/water partitioning and inclusion in detergent micelles of the oligo‐Oic peptides. The results showed that the hydrophobicity is remarkably enhanced in longer oligomeric sequences, and the oligo‐Oic peptides with 3 to 4 residues and higher are specific towards hydrophobic environments. This contrasts significantly to the parent oligoproline peptides, which were moderately hydrophilic. With these findings, we have demonstrated that the polyproline‐II structure is compatible with nonpolar media, whereas additional manipulations of the terminal functionalities feature solubility in extremely nonpolar solvents such as hexane.