The construction of beta-amino acid-containing peptides that fold to tertiary structures in solution remains challenging. Two model miniproteins, namely, Trp-cage and FSD, were scanned using constrained beta-amino acid in order...

Numerous beta‐amino acid containing peptides forming secondary structures have been already described, however the design of higher‐order structures remains poorly explored. The methodology allowing construction of sequence patterns containing few rigid secondary element was proposed and experimentally validated. On the basis of 9/10/9/12‐helix containing cis‐2‐aminocyclopentanecarboxylic acid (cis‐ACPC) residues arranged in an ααββ sequence pattern, a conformationally stable helix‐turn‐helix structure was designed. The connection between two helices was also constructed using cis‐ACPC residues. Five examples of designed peptides were obtained and analyzed using circular dichroism and nuclear magnetic resonance spectroscopy, which confirmed the assumed way of folding. The NMR structure was calculated for the peptide with the highest number of non‐sequential contacts.

A new miniprotein built from three helices, including one structure based on a ααβαααβ sequence pattern was developed. Its crystal structure revealed a compact conformation with a well-packed hydrophobic core...