Design and Structural Characterization of Amphiphilic beta-Peptide Assemblies

There is growing interest in the design of molecules that undergo predictable self-assembly. Bioinspired oligomers with well-defined conformational propensities, "foldamers" have potential advantages comparable to those of peptides, being composed of versatile building blocks, capable of forming self-assembled structures. In this study we designed and synthesized alfa/beta peptide oligomers composed of 1:1 alternation of alfa and beta subunits along the backbone. Such sequences were assumed to prefer amphiphilic conformations at hydrophilic/hydrophobic interfaces in addition to having the potential to organize into ordered monolayer structures at interfaces. Grazing incidence X-ray diffraction (GIXD) measurements showed the assemblies exhibited in general, diffraction features similar to those of beta-sheet-forming alfa-peptides. Significant differences were found between self-assemblies of all negatively and all positively charged oligomers. The diffraction data allowed the construction of a detailed model of an antiparallel alfa/beta-peptide sheet in a unique pleated structure. One of the alfa/beta-peptide assemblies displayed high stability, unparalleled among previously studied alfa-peptides assemblies. This result showed that positioning of ionic side chains along the backbone can exert a profound effect on the propensity to self-assemble, presumably because of intramolecular backbone dipole-charge interactions. Two zwitterionic oligomers were designed to favor in 1:1 molar ration mixture, self assembly in parallel arrangement. ATR-FTIR spectra showed spectra typical to parallel beta-sheet secondary structure in systems with pure alfa-residue backbones. In this study we have developed a new family of amphiphilic alfa/beta-peptides with high propensity for self-assembly which were found to be profoundly sensitive to ionic side chain charges positioned along their backbones.