Cavitands are effective templates for inducing stability and nativelike structure in de novo four-helix bundles

The design, synthesis and characterization of eight cavitand-based de novo four-helix bundles are presented. The proteins, each containing the basis sequence EELLKKLEELLKKG, are determined to be highly helical and exhibit extreme stability against the denaturant guanidine hydrochloride (GuHCl). The presence of flexible cavitand-peptide linkers, however, caused the helical structures to become more susceptible to GuHCl denaturation.