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.

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.

The creation of self-assembling microscale architectures that possess new and useful physical properties remains a significant challenge. Herein we report that an 11-helical foldamer self-assembles in a controlled manner to form a series of 3D foldectures with unusual three-fold symmetrical shapes that are distinct from those generated from 12-helical foldamers. The foldamer packing motif was revealed by powder X-ray diffraction technique, and provides an important link between the molecular-level symmetry and the microscale morphologies. The utility of foldectures with hollow interiors as robust and well-defined supramolecular hosts was demonstrated for inorganic, organic, and even protein guests. This work will pave the way for the design of functional foldectures with greater 3D shape diversity and for the development of biocompatible delivery vehicles and containment vessels.

No abstract

A novel nonpeptidic reverse-turn scaffold containing urea fragments that are connected by a conformationally constrained D-prolyl-cis-1,2-diaminocyclohexane (D-Pro-DACH) linker is reported. The scaffold adopts a well-defined reverse-turn conformation that is stabilized by dual intramolecular hydrogen bonding in both solution and solid states.