Foldectures: 3D Molecular Architectures from Self-Assembly of Peptide Foldamers

Abstract

The wide range of fascinating supramolecular architectures found in nature, from DNA double helices to giant protein shells, inspires researchers to mimic the diverse shapes and functions of natural systems. Thus, a variety of artificial molecular platforms have been developed by assembling DNA-, peptide-, and protein-based building blocks for medicinal and biological applications. There has also been a significant interest in the research of non-natural oligomers (i.e., foldamers) that fold into well-defined secondary structures analogous to those found in proteins, because the assemblies of foldamers are expected not only to form biomimetic supramolecular architectures that resemble those of nature but also to display unique functions and unprecedented topologies at the same time due to their different folding propensities from those of natural building blocks. Foldamer-based supramolecular architectures have been reported in the form of nanofibers, nanochannels, nanosheets, and finite three-dimensional (3D) shapes. We have developed a new class of crystalline peptidic materials termed "foldectures" (a compound of foldamer and architecture) with unprecedented topological complexity derived from the rapid and nonequilibrium aqueous phase self-assembly of foldamers. In this Account, we discuss the morphological features, molecular packing structures, physical properties, and potential applications of foldectures. Foldectures exhibit well-defined, microscale, homogeneous, and finite structures with unique morphologies such as windmill, tooth, and trigonal bipyramid shapes. The symmetry elements of the morphologies vary with the foldamer building blocks and are retained upon surfactant-assisted shape evolution. Structural characterization by powder X-ray diffraction (PXRD) revealed the molecular packing structures, suggesting how the foldamer building blocks assembled in the 3D structure. The analysis by PXRD showed that intermolecular hydrogen bonding connects foldamers in head-to-tail fashion, while hydrophobic attraction plays a role in arranging foldamers in parallel, antiparallel, or cholesteric phase-like manners. Each packing structure from the foldamer building blocks possesses distinct symmetry elements that are directly expressed in the 3D morphologies. Because of their well-ordered molecular packing structures, foldectures exhibit facet-dependent surface characteristics and anisotropic magnetic susceptibility. The facet-dependent surface property was harnessed to synthesize anisotropic metal nanoparticle-foldecture composites, and the anisotropic magnetic susceptibility enables foldectures to undergo real-time alignment and rotating motion in response to an external magnetic field. By means of their unusual shapes and properties, foldectures have been demonstrated to mimic the functionality of natural systems such as magnetosomes or carboxysomes. Further development of foldectures using higher-order building units, complicated packing motifs, and functional moieties could provide a novel biocompatible pl...

Molecular simulations of self-assembling bio-inspired supramolecular systems and their connection to experiments

“…However, as the chemical space for bio-inspired nanostructures is enormous, it would be particularly interesting to simplify the effort of discovering new bionanostructures by predictive computational approaches. The rational design of small to medium-sized building blocks that assemble has seen many successes from the field of foldamers, 212 , 233 – 236 single molecules that fold via non-covalent interactions, often through intramolecular recognition motifs using similar interactions as in the general field of self-assembly (H-bonds, π-stacking etc. ).…”

Helical polysaccharides

“…Sequence controlled oligomers (i.e., foldamers) can be designed to achieve specific control over the secondary structure. Extremely stable structures resembling natural proteins or with completely new geometries can be obtained, based on relatively short sequences . Lack of reliable methods to synthesize well‐defined oligo and polysaccharide structures hampered the formation of sugar‐based foldamers.…”

Self-Assembly of Constrained Cyclic Peptides Controlled by Ring Size

“…3,4 Commonly used building blocks for peptide self-assembly include dipeptide of phenylalanine (FF) or their derivatives, 4,5 D,L-cyclic peptides, 6 peptide amphiphiles, 7 collagens, 8 coiled coils, 9 and foldectures. 10 These materials have shown great potential for many applications, including energy storage and conversion, 11,12 optical devices, 13,14 and nanomedicine. 15,16 The manipulation of cyclic peptide assembly is emerging as a new direction for hierarchical nanostructure fabrication.…”