Unprecedented Molecular Architectures by the Controlled Self‐Assembly of a β‐Peptide Foldamer

Abstract

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...

Bio-inspired supramolecular self-assembly towards soft nanomaterials

“…Although a variety of peptide-based scaffolds have been studied, most of the reported peptides self-assemblies are limited to round shapes such as spheres, tubes, and rods. In a recent work [113], Lee et al reported the first example of finite molecular architectures formed by the self-assembly of a helical β-peptide in aqueous solution (Fig. 10).…”

“…(Reproduced with permission from Ref. [113], Copyright 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)…”

A Hollow Foldecture with Truncated Trigonal Bipyramid Shape from the Self‐Assembly of an 11‐Helical Foldamer

“…[1] As the concentration of P123 was increased, an evolution in foldecture shapes away from the primitive shape F 0 was observed. [1] As the concentration of P123 was increased, an evolution in foldecture shapes away from the primitive shape F 0 was observed.…”

“…[1] An otable architectural feature shared by these assemblies is the presence of ac ommon four-fold symmetry axis despite the different and unusual 3D shapes,s uch as windmill, petal, square bar, molar tooth, and rectangular tube. [1] An otable architectural feature shared by these assemblies is the presence of ac ommon four-fold symmetry axis despite the different and unusual 3D shapes,s uch as windmill, petal, square bar, molar tooth, and rectangular tube.…”

A Hollow Foldecture with Truncated Trigonal Bipyramid Shape from the Self‐Assembly of an 11‐Helical Foldamer

“…Foldectures are an ew class of crystalline peptidic material with unprecedented topological complexity derived from the rapid and non-equilibrium aqueous phase self-assembly of foldamers.W ehave demonstrated that it is feasible to obtain av ariety of three-dimensional (3D) foldecture shapes from as et of b-peptide foldamers with identical 12-helical secondary structures by simple variation of the self-assembly conditions. [1] An otable architectural feature shared by these assemblies is the presence of ac ommon four-fold symmetry axis despite the different and unusual 3D shapes,s uch as windmill, petal, square bar, molar tooth, and rectangular tube. This observation raised the fundamental question of whether 4-fold symmetry is intrinsic to foldectures or is instead determined by foldamer secondary structure,w ith new and useful foldecture morphologies potentially available through the choice of ad ifferent foldamer secondary structure.S uch ar elationship,i fp resent, would offer ag eneral and useful method to design foldectures using foldamer secondary structure as the basic unit, with specific shapes and diverse functions that more closely resemble biological architectures.…”