Sheet‐Like Assemblies of Charged Amphiphilic α/β‐Peptides at the Air–Water Interface

There is growing interest in the design of molecules that undergo predictable self‐assembly. Bioinspired oligomers with well‐defined conformational propensities are attractive from this perspective, since they can be constructed from diverse building blocks, and self‐assembly can be directed by the identities and sequence of the subunits. Here we describe the structure of monolayers formed at the air–water interface by amphiphilic α/β‐peptides with 1:1 alternation of α‐ and β‐amino acid residues along the backbone. Two of the α/β‐peptides, one a dianion and the other a dication, were used to determine differences between self‐assemblies of the net negatively and positively charged oligomers. Two additional α/β‐peptides, both zwitterionic, were designed to favor assembly in a 1:1 molar ratio mixture with parallel orientation of neighboring strands. Monolayers formed by these α/β‐peptides at the air–water interface were characterized by surface pressure–area isotherms, grazing incidence X‐ray diffraction (GIXD), atomic force microscopy and ATR‐FTIR. GIXD data indicate that the α/β‐peptide assemblies exhibited diffraction features similar to those of β‐sheet‐forming α‐peptides. The diffraction data allowed the construction of a detailed model of an antiparallel α/β‐peptide sheet with a unique pleated structure. One of the α/β‐peptide assemblies displayed high stability, unparalleled among previously studied assemblies of α‐peptides. ATR‐FTIR data suggest that the 1:1 mixture of zwitterionic α/β‐peptides assembled in a parallel arrangement resembling that of a typical parallel β‐sheet secondary structure formed by α‐peptides. This study establishes guidelines for design of amphiphilic α/β‐peptides that assemble in a predictable manner at an air–water interface, with control of interstrand orientation through manipulation of Coulombic interactions along the backbone.