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 airwater interface by amphiphilic alpha/beta-peptides with 1:1 alternation of a- and beta-amino acid residues along the backbone. Two of the alpha/beta-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 alpha/beta-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 alpha/beta-peptides at the airwater interface were characterized by surface pressurearea isotherms, grazing incidence X-ray diffraction (GIXD), atomic force microscopy and ATR-FTIR. GIXD data indicate that the alpha/beta-peptide assemblies exhibited diffraction features similar to those of beta-sheet-forming a-peptides. The diffraction data allowed the construction of a detailed model of an antiparallel alpha/beta-peptide sheet with a unique pleated structure. One of the alpha/beta-peptide assemblies displayed high stability, unparalleled among previously studied assemblies of a-peptides. ATR-FTIR data suggest that the 1:1 mixture of zwitterionic alpha/beta-peptides assembled in a parallel arrangement resembling that of a typical parallel beta-sheet secondary structure formed by a-peptides. This study establishes guidelines for design of amphiphilic alpha/beta-peptides that assemble in a predictable manner at an airwater interface, with control of interstrand orientation through manipulation of Coulombic interactions along the backbone.