Molecular self-assembly is the spontaneous association of molecules into structured aggregates by which nature builds complex functional systems. While numerous examples have focused on 2D self-assembly to understand the underlying mechanism and mimic this process to create artificial nano- and microstructures, limited progress has been made toward 3D self-assembly on the molecular level. Here we show that a helical β-peptide foldamer, an artificial protein fragment, with well-defined secondary structure self-assembles to form an unprecedented 3D molecular architecture with a molar tooth shape in a controlled manner in aqueous solution. Powder X-ray diffraction analysis, combined with global optimization and Rietveld refinement, allowed us to propose its molecular arrangement. We found that four individual left-handed helical monomers constitute a right-handed superhelix in a unit cell of the assembly, similar to that found in the supercoiled structure of collagen.

The design of stimuli-responsive self-assembled molecular systems capable of undergoing mechanical work is one of the most important challenges in synthetic chemistry and materials science. Here we report that foldectures, that is, self-assembled molecular architectures of β-peptide foldamers, uniformly align with respect to an applied static magnetic field, and also show instantaneous orientational motion in a dynamic magnetic field. This response is explained by the amplified anisotropy of the diamagnetic susceptibilities as a result of the well-ordered molecular packing of the foldectures. In addition, the motions of foldectures at the microscale can be translated into magnetotactic behaviour at the macroscopic scale in a way reminiscent to that of magnetosomes in magnetotactic bacteria. This study will provide significant inspiration for designing the next generation of biocompatible peptide-based molecular machines with applications in biological systems.

Nature utilizes the self-assembly of monomeric units by multiple noncovalent interactions for the construction of complex functional systems.[1] In recent decades, a variety of peptide-based scaffolds, which range from simple aromatic dipeptides to small protein fragments, have been studied in order to understand the underlying mechanism and mimic this process to create artificial nano-and microstructures. [2][3][4][5][6] Because of the intrinsic large conformational flexibility of short-length peptides, amphiphilic, [7,8] or cyclic [9] scaffolds have been typically employed to ensure the formation of welldefined self-assembled structures. However, in contrast to the morphologies found in inorganic nanostructures, [10] the morphologies of the peptide-based self-assembled nano-and microstructures are limited to round shapes such as spheres, tubes, and rods.[11] The ability to construct biocompatible peptide-based molecular architectures with anisotropic shapes should expand the possibilities for the design of molecular machines for diverse applications in biological and materials science.[12] Such a construction should be possible if a molecular design principle for monomeric units held together by comparable intermolecular interactions in three orthogonal directions was available; however, currently this is not the case. [13] On the other hand, b peptides (oligomers of b amino acids) are excellent artificial peptides that can mimic proteinlike secondary structures such as helices, strands, and turns. [14] The self-associating behavior of b peptides have recently been investigated, [15][16][17][18] but the construction of higher-order structures with specific morphologies is still in its infancy. Herein we report the first example of highly homogeneous, welldefined, and finite molecular architectures formed by the selfassembly of a helical b peptide in aqueous solution. The 3D shapes of the assembled nano-and microstructures can be controlled by simply changing the experimental conditions.We used a homo-oligomer of trans-(S,S)-2-aminocyclopentanecarboxylic acid (ACPC) as a building block for the self-assembly. This particular b peptide resembles an a-helical peptide in terms of handedness, helical pitch, and the direction of the macrodipole moment, but is known to adopt a more stable and unique helical conformation through intramolecular 12-membered hydrogen bonding between C=O (i) and NÀH (i + 3) (the so-called 12-helix) in both solid state and solution, if the number of monomers exceeds approximately six residues (Figure 1 a). [19] Figure 1 b shows the chemical structure of the ACPC heptamer (ACPC 7 ), which is a highly hydrophobic molecule (aspect ratio % 2), because the methylene units of the cyclopentane rings are displayed over the helical faces, and both the N-and Ctermini are protected by a tert-butyloxycarbonyl (Boc) and a benzyl group, respectively. The possible modes of selfassembly of ACPC oligomers are illustrated in Figure 1 c. With this simple design, ACPC 7 should adopt a stable righthanded 12-heli...

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...

The synthesis of microscale, polyhedrally shaped, soft materials with anisotropic surface functionality by a bottom-up approach remains a significant challenge. Herein we report a microscale molecular architecture (foldecture) with facet-dependent surface characteristics that can potentially serve as a well-defined catalytic template. Rhombic rod shaped foldectures with six facets were obtained by the aqueous self-assembly of helical β-peptide foldamers with a C-terminal carboxylic acid. An analysis of the molecular packing by X-ray diffraction revealed that carboxylic acid groups were exposed exclusively on the two (001) rhombic facets due to antiparallel packing of the helical peptides. A surface energy calculation by molecular dynamics simulation was performed to provide a plausible explanation for the development of anisotropy during foldecture formation. The expected facet-selective surface properties of the foldecture were experimentally confirmed by selective deposition of metal nanoparticles on the (001) facets, leading to a new class of sequentially constructed, heterogeneous "foldecture core" materials.

Kampf gegen Windmühlen: Durch die Selbstorganisation eines kurzen helicalen β‐Peptids in wässriger Lösung wurden hochgradig homogene, wohldefinierte und endliche „Windmühlen“ und quadratischen Stäbchen gleichende supramolekulare Architekturen gebildet (siehe Bild). Die reproduzierbare Bildung der neuartigen 3D‐Formen konnte durch den Einsatz unterschiedlicher Konzentrationen eines Tensids gesteuert werden.

Amphipathic water-soluble helices formed from synthetic peptides or foldamers are promising building blocks for the creation of self-assembled architectures with non-natural shapes and functions. While rationally designed artificial quaternary structures such as helix bundles have been shown to contain preformed cavities suitable for guest binding, there are no examples of adaptive binding of guest molecules by such assemblies in aqueous conditions. We have previously reported a foldamer 6-helix bundle that contains an internal nonpolar cavity able to bind primary alcohols as guest molecules. Here, we show that this 6-helix bundle can also interact with larger, more complex guests such as n-alkyl glycosides. X-ray diffraction analysis of co-crystals using a diverse set of guests together with solution and gas-phase studies reveals an adaptive binding mode whereby the apo form of the 6-helix bundle undergoes substantial conformational change to accommodate the hydrocarbon chain in a manner reminiscent of glycolipid transfer proteins in which the cavity forms upon lipid uptake. The dynamic nature of the self-assembling and molecular recognition processes reported here marks a step forward in the design of functional proteomimetic molecular assemblies.

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