RESUMO
The steric zipper is a common hydrophobic packing structure of peptide side chains that forms between two adjacent ß-sheet layers in amyloid and related fibrils. Although previous studies have revealed that peptide fragments derived from native protein sequences exhibit steric zipper structures, their de novo designs have rarely been studied. Herein, steric zipper structures were artificially constructed in the crystalline state by metal-induced folding and assembly of tetrapeptide fragments Boc-3pa-X1-3pa-X2-OMe (3pa: ß-(3-pyridyl)-l-alanine; X1 and X2: hydrophobic amino acids). Crystallographic studies revealed two types of packing structures, interdigitation and hydrophobic contact, that result in a class 1 steric zipper geometry when the X1 and X2 residues contain alkyl side chains. Furthermore, a class 3 steric zipper geometry was also observed for the first time among any reported steric zippers when using tetrapeptide fragments with (X1, X2) = (Thr, Thr) and (Phe, Leu). The system could also be extended to a knob-hole-type zipper using a pentapeptide sequence.
Assuntos
Elétrons , Nanoestruturas , Raios X , Estrutura Secundária de Proteína , Modelos Moleculares , Peptídeos/química , Amiloide/química , Difração de Raios XRESUMO
Despite the frequent occurrence of knotted frameworks in protein structures, the latent potential of peptide strands to form entangled structures is rarely discussed in peptide chemistry. Here we report the construction of highly entangled molecular topologies from Ag(I) ions and tripeptide ligands. The efficient entanglement of metal-peptide strands and the wide scope for design of the amino acid side chains in these ligands enabled the construction of metal-peptide 91 torus knots and 1012 torus links. Moreover, steric control of the peptide side chain induced ring opening and twisting of the torus framework, which resulted in an infinite toroidal supercoil nanostructure.
RESUMO
Porous metal complexes enable single-crystal X-ray crystallographic observation of included guests or reaction intermediates through simple soaking with the guests/substrates. Previous studies on this technique have often encountered difficulties in the observation of chiral structures because the host frameworks had no chirality. We synthesized a new metal-peptide porous complex through a folding-and-assembly strategy and utilized the chiral pore for trapping chiral guests. Chiral alcohols and ketones were successfully included within the pore. Crystallographic analyses clearly revealed not only their chemical structures but also chiral transformation events within the pore such as fixed conformations or an unstable hemiacetal formation.
Assuntos
Cristalografia por Raios X/métodos , Metais/química , Peptídeos/química , Conformação Molecular , EstereoisomerismoRESUMO
The de novo construction of repeat proteins has received much attention from biologists and chemists, yet that of a ß-barrel structure, one of the most well-known classes, has not been accomplished to date. Here, we report the first chemical construction of a ß-barrel tertiary structure with a pore through a combination of peptide folding and metal-directed self-assembly. Coordination of zinc salts to an eight-residue peptide fragment bearing ß-strand- and loop-forming sequences resulted in a ß-barrel in which six-stranded cylindrical antiparallel ß-sheets formed a hydrophobic pore with a specific shape.
Assuntos
Compostos Macrocíclicos/química , Peptídeos/química , Conformação Proteica em Folha beta , Zinco/química , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Porosidade , Dobramento de Proteína , Estrutura Terciária de ProteínaRESUMO
There is broad interest in molecular encapsulation as such systems can be utilized to stabilize guests, facilitate reactions inside a cavity, or give rise to energy-transfer processes in a confined space. Detailed understanding of encapsulation events is required to facilitate functional molecular encapsulation. In this contribution, it is demonstrated that Ir and Rh-Cp-type metal complexes can be encapsulated inside a self-assembled M6 L4 metallocage only in the presence of an aromatic compound as a second guest. The individual guests are not encapsulated, suggesting that only the pair of guests can fill the void of the cage. Hence, selective co-encapsulation is observed. This principle is demonstrated by co-encapsulation of a variety of combinations of metal complexes and aromatic guests, leading to several ternary complexes. These experiments demonstrate that the efficiency of formation of the ternary complexes depends on the individual components. Moreover, selective exchange of the components is possible, leading to formation of the most favorable complex. Besides the obvious size effect, a charge-transfer interaction may also contribute to this effect. Charge-transfer bands are clearly observed by UV/Vis spectrophotometry. A change in the oxidation potential of the encapsulated electron donor also leads to a shift in the charge-transfer energy bands. As expected, metal complexes with a higher oxidation potential give rise to a higher charge-transfer energy and a larger hypsochromic shift in the UV/Vis spectrum. These subtle energy differences may potentially be used to control the binding and reactivity of the complexes bound in a confined space.
RESUMO
A topologically complex peptide [4]catenane with the crossing number of 12 was synthesized by a folding and assembly strategy wherein the folding and metal-directed self-assembly of a short peptide fragment occur simultaneously. The latent Ω-looped conformation of the Pro-Gly-Pro sequence was found only when pyridines at the C- and N-termini coordinatively bind metal ions (Ag(I) or Au(I) ). Crystallographic studies revealed that the Ω-looped motifs formed four M3 L3 macrocycles that were intermolecularly entwined to generate an unprecedented peptide [4]catenane topology.
Assuntos
Antracenos/química , Peptídeos/química , Ressonância Magnética Nuclear Biomolecular , Dobramento de ProteínaRESUMO
Guest-induced M18 L6 -M24 L8 capsule-capsule conversion is reported. Both capsules are composed of Pd(II) ethylenediamine units (M) and 1,3,5-tris(3,5-pyrimidyl)pyrimidine (L), and form trigonal bipyramidal (M18 L6 ) and octahedral (M24 L8) closed-shell structures with huge hydrophobic inner spaces. The M18 L6 trigonal bipyramid is converted to the M24 L8 octahedron through encapsulation of large aromatic guests, with the latter capsule possessing a cavity volume three times larger than the former. Despite the dynamic properties of the capsule host, the encapsulated guests are difficult to extract and are thus isolated from the external environment.
RESUMO
Self-assembled coordination cages can be employed as a molecular press, where the bowl-shaped guest corannulene (C20H10) is significantly flattened upon inclusion within the hydrophobic cavity. This is demonstrated by the pairwise inclusion of corannulene with naphthalene diimide as well as by the dimer inclusion of bromocorannulene inside the box-like host. The compressed corannulene structures are unambiguously revealed by single-crystal X-ray analysis.
RESUMO
Mutual induced fit is an important phenomenon in biological molecular recognition, but it is still rare in artificial systems. Here we report an artificial host-guest system in which a flexible calix[4]arene is enclathrated in a dynamic self-assembled host and both molecules mutually adopt specific three-dimensional structures. NMR data revealed the conformational changes, and crystallographic studies clearly established the precise structures at each stage.
Assuntos
Calixarenos/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação MolecularRESUMO
Short peptide helices have attracted attention as suitable building blocks for soft functional materials, but they are rarely seen in crystalline materials. A new artificial nanoassembly of short peptide helices in the crystalline state is presented in which peptide helices are arranged three-dimensionally by metal coordination. The folding and assembly processes of a short peptide ligand containing the Gly-Pro-Pro sequence were induced by silver(I) coordination in aqueous alcohol, and gave rise to a single crystal composed of polyproline II helices. Crystallographic studies revealed that this material possesses two types of unique helical nanochannel; the larger channel measures more than 2â nm in diameter. Guest uptake properties were investigated by soaking the crystals in polar solutions of guest molecules; anions, organic chiral molecules, and bio-oligomers are effectively encapsulated by this peptide-folded porous crystal, with moderate to high chiral recognition for chiral molecules.
Assuntos
Complexos de Coordenação/metabolismo , Nanotubos/química , Peptídeos/metabolismo , Prata/química , Cápsulas , Complexos de Coordenação/química , Cristalografia por Raios X , Modelos Moleculares , Peptídeos/química , Dobramento de Proteína , Estrutura Secundária de ProteínaRESUMO
Although square-planar ML4 units are essential building blocks for coordination cages and capsules, the non-covalent control of the chirality and helicity of the resultant nanostructures is quite difficult. Here we report the helicity control of an M2L4 polyaromatic capsule, formed from metal ions with square-planar coordination geometry and bent bispyridine ligands, through stereoselective CH-π interactions with monosaccharide derivatives. Thanks to host-guest CH-π multi-interactions, one molecule of various permethylated monosaccharides is quantitatively bound by the capsule in water (K a up to >108 M-1). In the polyaromatic cavity, among them, the selective binding of a ß-glucose derivative (>80 : 20 ratio) is demonstrated from a mixture of the α/ß-glucoses, through the equatorial-selective recognition of the anomeric (C1) group. A similar stereoselective binding is accomplished from an α/ß-galactose mixture. Interestingly, single equatorial/axial configurations on the bound monosaccharides can regulate the helical conformation of the capsule in water, confirmed by CD, NMR, and theoretical analyses. An intense capsule-based Cotton effect is exclusively observed upon encapsulation of the permethylated α-glucose (>20-fold enhancement as compared to the ß-glucose derivative), via the induction of a single-handed host helicity to a large extent. Inverse capsule helicity is induced by the binding of a ß-galactose derivative under the same conditions.
RESUMO
Precise recognition of peptides is a daunting task owing to the substantial number of available amino acids and their combination into various oligo/polymeric structures in addition to the high hydration of their flexible frameworks. Here, we report the selective recognition of a dipeptide through a closed cavity strategy, in contrast to previous synthetic receptors with open cavities. A polyaromatic receptor with a virtually isolated, hydrophobic cavity exclusively binds one molecule of phenylalanine dipeptide from a mixture with its amino acid and tripeptide in water via multiple CH-π and hydrogen-bonding interactions in the complementary cavity. The binding selectivity persists even in the presence of other dipeptides, such as leucine-leucine, leucine-phenylalanine, tyrosine-phenylalanine, tryptophan-tryptophan, and aspartame, revealed by NMR/MS-based competitive binding experiments. ITC studies reveal that the selective binding of the phenylalanine dipeptide is relatively strong (Ka = 1.1 × 105 M-1) and an enthalpically and entropically favorable process (ΔH = -11.7 kJ mol-1 and TΔS = 17.0 kJ mol-1). In addition, the present receptor can be used for the emission detection of the dipeptide through a combination with a fluorescent dye in water.
RESUMO
Artificial mimicry of α-helices offers a basis for development of protein-protein interaction antagonists. Here we report a new type of unnatural peptidic backbone, containing α-, ß-, and γ-amino acid residues in an αγααßα repeat pattern, for this purpose. This unnatural hexad has the same number of backbone atoms as a heptad of α residues. Two-dimensional NMR data clearly establish the formation of an α-helix-like conformation in aqueous solution. The helix formed by our 12-mer α/ß/γ-peptide is considerably more stable than the α-helix formed by an analogous 14-mer α-peptide, presumably because of the preorganized ß and γ residues employed.
Assuntos
Peptídeos/química , Água/química , Sequência de Aminoácidos , Aminoácidos/química , Biomimética , Dicroísmo Circular , Dados de Sequência Molecular , Estrutura Secundária de Proteína , Soluções/químicaRESUMO
Hydrogen bond (H-bond) formation in water has been a challenging task because water molecules are constant competitors. In biological systems, however, stable H-bonds are formed by shielding the H-bonding sites from the competing water molecules within hydrophobic pockets. Inspired by the nature's elaborated way, we found that even mononucleotides (G and C) can form the minimal G x C Watson-Crick pair in water by simply providing a synthetic cavity that efficiently shields the Watson-Crick H-bonding sites. The minimal Watson-Crick structure in water was elucidated by NMR study and firmly characterized by crystallographic analysis. The crystal structure also displays that, within the cavity, coencapsulated anions and solvents efficiently mediate the minimal G x C Watson-Crick pair formation. Furthermore, the competition experiments with the other nucleobases clearly revealed the evident selectivity for the G x C base pairing in water. These results show the fact that a H-bonded nucleobase pair was effectively induced and stabilized in the local environment of an artificial hydrophobic cavity.
Assuntos
Pareamento de Bases , Interações Hidrofóbicas e Hidrofílicas , Água/química , Cristalografia por Raios X , DNA/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , SoluçõesRESUMO
Short peptides were induced into alpha-helix conformations in water through enclathration to an artificial hydrophobic cavity. Peptides with two aromatic residues showed high affinity for the host, and these intermolecular aromatic-aromatic interactions specifically drove the helical folding of short peptides.
Assuntos
Interações Hidrofóbicas e Hidrofílicas , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Dobramento de Proteína , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Água/químicaRESUMO
Cavity creation is a key to the origin of biological functions. Small cavities such as enzyme pockets are created simply through liner peptide folding. Nature can create much larger cavities by threading and entangling large peptide rings, as learned from gigantic virus capsids, where not only chemical structures but the topology of threaded rings must be controlled. Although interlocked molecules are a topic of current interest, they have for decades been explored merely as elements of molecular machines, or as a synthetic challenge. No research has specifically targeted them for, and succesfully achieved, cavity creation. Here we report the emergence of a huge capsular framework via multiple threading of metal-peptide rings. Six equivalent C4-propeller-shaped rings, each consisting of four oligopeptides and Ag+, are threaded by each other a total of twelve times (crossing number: 24) to assemble into a well-defined 4 nm-sized sphere, which acts as a huge molecular capsule.
Assuntos
Cápsulas/química , Metais , Peptídeos/química , Antracenos/química , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Conformação Proteica , Piridinas , Prata/químicaRESUMO
With increasing ring-crossing number (c), knot theory predicts an exponential increase in the number of topologically different links of these interlocking structures, even for structures with the same ring number (n) and c. Here, we report the selective construction of two topologies of 12-crossing peptide [4]catenanes (n = 4, c = 12) from metal ions and pyridine-appended tripeptide ligands. Two of the 100 possible topologies for this structure are selectively created from related ligands in which only the tripeptide sequence is changed: one catenane has a T2-tetrahedral link and the other a three-crossed tetrahedral link. Crystallographic studies illustrate that a conformational difference in only one of the three peptide residues in the ligand causes the change in the structure of the final tetrahedral link. Our results thus reveal that peptide-based folding and assembly can be used for the facile bottom-up construction of 3D molecular objects containing polyhedral links.
RESUMO
Concerted folding and assembly processes are necessary for protein self-assembly, yet such a concerted strategy has rarely been attempted by synthetic chemists. In this work, we have created a new porous peptide structure through a coordination-driven folding-and-assembly strategy. A porous framework with 1.5â nm-sized pores and a PII helical peptide scaffold was successfully obtained by complexation of AgNTf2 and tripeptide ligands containing the Gly-Pro-Pro sequence. The pores were modified in various ways with retention of the latent PII helical conformation of the peptide ligand.
Assuntos
Peptídeos/química , Dobramento de Proteína , Estrutura Molecular , Peptídeos/síntese química , Porosidade , Propriedades de SuperfícieRESUMO
A new M20L8 coordination capsule was synthesized. Owing to the structural flexibility and dynamic properties, the capsule showed wide scope for guest encapsulation. Furthermore, unique capsule-bowl conversion occurred upon a large guest encapsulation or a guest reaction.