Protein dynamics have been suggested to have a crucial role in biomolecular recognition, but the precise molecular mechanisms remain unclear. Herein, we performed single-molecule fluorescence resonance energy transfer measurements for wild-type maltose-binding protein (MBP) and its variants to demonstrate the interplay of conformational dynamics and molecular recognition. Kinetic analysis provided direct evidence that MBP recognizes a ligand through an 'induced-fit' mechanism, not through the generally proposed selection mechanism for proteins with conformational dynamics such as MBP. Our results indicated that the mere presence of intrinsic dynamics is insufficient for a 'selection' mechanism. An energetic analysis of ligand binding implicated the critical role of conformational dynamics in facilitating a structural change that occurs upon ligand binding.

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.

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...

Chiral beta-substituted gamma-butyrolactones are known to be important intermediates for many biologically active compounds such as gamma-aminobutyric acid (GABA) derivatives and lignans. We have developed a general, convenient, and scalable synthetic method for enantiomerically pure beta-substituted gamma-butyrolactones, with either configuration, via nucleophilic cyclopropane ring opening of (1S,5R)- or (1R,5S)-bicyclic lactone followed by decarbethoxylation. The utility of our method was demonstrated by streamlined synthesis of pregabalin ((S)-3-isobutyl-gamma-aminobutyric acid), an anticonvulsant drug for the treatment of peripheral neuropathic pain.