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1.
The folding and aggregation behavior of a pair of oligo(phenylene ethynylene) (OPE) foldamers are investigated by means of UV/Vis absorption and circular dichroism spectroscopy. With identical OPE backbones, two foldamers, 1 with alkyl side groups and 2 with triethylene glycol side chains, manifest similar helical conformations in solutions in n‐hexane and methanol, respectively. However, disparate and competing folding and aggregation processes are observed in alternative solvents. In cyclohexane, oligomer 1 initially adopts the helical conformation, but the self‐aggregation of unfolded chains, as a minor component, gradually drives the folding–unfolding transition eventually to the unfolded aggregate state completely. In contrast, in aqueous solution (CH3OH/H2O) both folded and unfolded oligomer 2 appear to undergo self‐association; aggregates of the folded chains are thermodynamically more stable. In solutions with a high H2O content, self‐aggregation among unfolded oligomers is kinetically favored; these oligomers very slowly transform into aggregates of helical structures with greater thermodynamic stability. The folded–unfolded conformational switch thus takes place with the free (nonaggregated) molecules, and the very slow folding transition is due to the low concentration of molecularly dispersed oligomers.  相似文献   

2.
A series of conjugated oligo(p-phenylene-ethynylene) (OPE) molecules with backbone conformations (that is, the relative orientations of the contained phenylene units) controlled by competitive intramolecular hydrogen bonds to be either co-planar or random were synthesised and studied. In these oligomers, carboxylate and amido substituents were attached to alternate phenylene units in the OPE backbone. These functional groups were able to form intramolecular hydrogen bonds between neighbouring phenylene units. Thereby, all phenylene units in the backbone were confined in a co-planar conformation. This planarised structure featured a more extended effective conjugation length than that of regular OPEs with phenylene units adopting random orientation due to a low rotational-energy barrier. However, if a tri(ethylene glycol) (Tg) side chain was appended to the amido group, it enabled another type of intramolecular hydrogen bond, formed by the Tg chain folding back and the contained ether oxygen atom competing with the ester carbonyl group as the hydrogen-bond acceptor. The outcome of this competition was proven to depend on the length of the alkylene linker joining the ether oxygen atom to the amido group. Specifically, if the Tg chain folded back to form a five-membered cyclic structure, this hydrogen-bonding motif was sufficiently robust to overrule the hydrogen bonds between adjacent phenylene units. Consequently, the oligomers assumed non-planar conformations. However, if the side chain formed a six-membered ring by hydrogen bonding with the amido NH group, such a motif was much less stable and yielded in the competition with the ester carbonyl group from the adjacent phenylene unit. Thus, the hydrogen bonds between the phenylene units remained, and the co-planar conformation was manifested. In our system, the hydrogen bonds formed by the back-folded Tg chain and amido NH group relied on a single oxygen atom as the hydrogen-bond acceptor. The additional oxygen atoms in the Tg chain made a negligible contribution. A bifurcated hydrogen-bond motif was unimportant. From our results, in combination with the results from an independent study by Meijer et al., it is evident that intramolecular hydrogen bonds involving back-folded oligo(ethylene glycol) moieties may differ in their structural details. Absorption spectroscopy served as a convenient yet sensitive technique for analysing hydrogen-bonding motifs in our study.  相似文献   

3.
N,N'-linked oligoureas with proteinogenic side chains are peptide backbone mimetics belonging to the gamma-peptide lineage. In pyridine, heptamer 4 adopts a stable helical fold reminiscent of the 2.6(14) helical structure proposed for gamma-peptide foldamers. In the present study, we have used a combination of CD and NMR spectroscopies to correlate far-UV chiroptical properties and conformational preferences of oligoureas as a function of chain length from tetramer to nonamer. Both the intensity of the CD spectra and NMR chemical shift differences between alphaCH2 diastereotopic protons experienced a marked increase for oligomers between four and seven residues. No major change in CD spectra occurred between seven and nine residues, thus suggesting that seven residues could be the minimum length required for stabilizing a dominant conformation. Unexpectedly, in-depth NMR conformational investigation of heptamer 4 in CD3OH revealed that the 2.5 helix probably coexists with partially (un)folded conformations and that Z-E urea isomerization occurs, to some degree, along the backbone. Removing unfavorable electrostatic interactions at the amino terminal end of 4 and adding one H-bond acceptor by acylation with alkyl isocyanate (4 --> 7) was found to reinforce the 2.5 helical population. The stability of the 2.5 helical fold in MeOH is further discussed in light of unrestrained molecular dynamics (MD) simulation. Taken together, these new data provide additional insight into the folding propensity of oligoureas in protic solvent and should be of practical value for the design of helical bioactive oligoureas.  相似文献   

4.
Monodisperse, cross‐conjugated perphenylated iso‐polydiacetylene (iso‐PDA) oligomers, ranging from monomer 15 to pentadecamer 25 , have been synthesized by using a palladium‐catalyzed cross‐coupling protocol. Structural characteristics elucidated by X‐ray crystallographic analysis demonstrate a non‐planar backbone conformation for the oligomers due to the steric interactions between alkylidene phenyl groups. The electronic absorption spectra of the oligomers show a slight red‐shift of the maximum absorption wavelength as the chain length increases from dimer 17 b to pentadecamer 25 , a trend that has saturated by the stage of nonamer 22 . Fluorescence spectroscopy confirms that the pendent phenyl groups present on the oligomer framework enhance emission, and the relative emission intensity consistently increases as a function of chain length n. The molecular third‐order nonlinearities, γ, for this oligomer series have been measured via differential optical Kerr effect (DOKE) detection and show a superlinear increase as a function of the oligomer chain length n. Molecular modeling and spectroscopic studies suggest that iso‐PDA oligomers (n>7) adopt a coiled, helical conformation in solution.  相似文献   

5.
Hydrogen bonding and the conformations of poly(alkyl acrylamides)   总被引:1,自引:0,他引:1  
The conformations of poly(alkyl acrylamide) oligomers in nonpolar solvents were studied using molecular dynamics techniques. Poly(methyl acrylamide) was found to collapse to a globule-like conformation at low temperatures; however, excluded volume effects inhibited the collapse of poly(octadecyl acrylamide). A high density of structured units, characterized by a trans-gauche-trans-trans-gauche-trans torsional sequence along the backbone, was noted in all simulations. Such units were found to create a particularly stable set of intramolecular hydrogen bonds. An oligomer constructed with these stable units was found to have significantly lower minimized energy than both the all-trans and the helical backbone conformations. The constructed conformation had lower Coulomb energy (more hydrogen bonds) than the all-trans conformation and lower dihedral energy (less backbone distortion) than the helical conformation. The propensity for poly(octadecyl acrylamide) to form hydrogen bonds introduced significant disorder into the orientation of the alkyl side chains. This disorder would inhibit crystallization and restrict the ability of such polymers to form epitaxial seeds for nucleating paraffin crystals.  相似文献   

6.
Tetrameric H10/12 helix stabilization was achieved by the application of aromatic side‐chains in β‐peptide oligomers by intramolecular backbone–side chain CH–π interactions. Because of the enlarged hydrophobic surface of the oligomers, a further aim was the investigation of the self‐assembly in a polar medium for the β‐peptide H10/12 helices. NMR, ECD, and molecular modeling results indicated that the oligomers formed by cis‐[1S,2S]‐ or cis‐[1R,2R]‐1‐amino‐1,2,3,4‐tetrahydronaphthalene‐2‐carboxylic acid (ATENAC) and cis‐[1R,2S]‐ or cis‐[1S,2R]‐2‐aminocyclohex‐3‐enecarboxylic acid (ACHEC) residues promote stable H10/12 helix formation with an alternating backbone configuration even at the tetrameric chain length. These results support the view that aromatic side‐chains can be applied for helical structure stabilization. Importantly, this is the first observation of a stable H10/12 helix with tetrameric chain‐length. The hydrophobically driven self‐assembly was achieved for the helix‐forming oligomers, seen as vesicles in transmission electron microscopy images. The self‐association phenomenon, which supports the helical secondary structure of these oligomers, depends on the hydrophobic surface area, because a higher number of aromatic side‐chains yielded larger vesicles. These results serve as an essential element for the design of helices relating to the H10/12 helix. Moreover, they open up a novel area for bioactive foldamer construction, while the hydrophobic area gained through the aromatic side‐chains may yield important receptor–ligand interaction surfaces, which can provide amplified binding strength.  相似文献   

7.
A molecular dynamics simulation of the folding of a short alanine-based helical peptide of 17 residues with three Glu...Lys (i, i + 4) salt bridge pairs, referred to as the AEK17 peptide, was carried out. The simulation gave an estimated simulation folding time of 2.5 ns, shorter than 12 ns for an alanine-based peptide of 16 residues with three Lys residues only, referred to as the AK16 peptide, simulated previously. After folded, the AEK17 peptide had a helical content of 77%, in excellent agreement with the experimentally determined value of 80%. An examination of the folding pathways of AEK17 indicated that the peptide proceeded via three-turn helix conformations more than the helix-turn-helix conformation in the folding pathways. An analysis of interactions indicated that the formation of hydrogen bonds between Lys residue side chains and backbone carbonyls is a major factor in the abundant conformation of the three-turn helix intermediate. The substitution of three Ala with Glu residues reduces the extent of hydrophobic interaction in alanine-based AK peptides with the result that the breaking of the interactions of Lys epsilon-NH3+(side chain)...C=O(backbone) is a major activation action for the AEK17 to achieve a complete fold, in contrast to the AK16 peptide, in which breaking non-native hydrophobic interaction is the rate-determining step.  相似文献   

8.
The structural properties of polyfluorenes (PF) are extremely sensitive to the choice of functionalizing side chains. Dioctyl substituted PF (PF8) adopts metastable structures that depend upon the thermal history and choice of solvents used in film forming conditions. We present a detailed study of the changes in the backbone and side chain morphology in PF8, induced by the various crystallographic phases, using Raman scattering techniques. The vibrational frequencies and intensities of fluorene oligomers are calculated using hybrid density-functional theory with a 3-21G(*) basis set. The alkyl side chains are modeled as limiting conformations: all anti, anti-gauche-gauche, and end gauche representations. The calculated vibrational spectra of single chain oligomers in conjunction with our experimental results demonstrate the beta phase, which is known to originate in regions of enhanced chain planarity as a direct consequence of the alkyl side chain conformation.  相似文献   

9.
The influence of valine side chains on the folding/unfolding equilibrium and, in particular, on the 314‐helical propensity of β3‐peptides were investigated by means of molecular‐dynamics (MD) simulation. To that end, the valine side chains in two different β3‐peptides were substituted by leucine side chains. The resulting four peptides, of which three have never been synthesized, were simulated for 150 to 200 ns at 298 and 340 K, starting from a fully extended conformation. The simulation trajectories obtained were compared with respect to structural preferences and folding behavior. All four peptides showed a similar folding behavior and were found to predominantly adopt 314‐helical conformations, irrespective of the presence of valine side chains. No other well‐defined conformation was observed at significant population in any of the simulations. Our results imply that β3‐peptides show a structural preference for 314‐helices independent of the branching nature of the side chains, in contrast to what has been previously proposed on the basis of circular‐dichroism (CD) measurements.  相似文献   

10.
11.
A series of m-phenylene ethynylene oligomers containing nonpolar, (S)-3,7-dimethyl-1-octanoxy side chains have been synthesized and studied. In apolar alkane solvents, oligomers of sufficient length (n > 10) were found to adopt a helical conformation with a large twist sense bias. In contrast, in chloroform the oligomers adopt a random coil conformation. Surprisingly, the strong twist sense bias was determined to be highly time dependent and is partially attributed to intermolecular aggregation.  相似文献   

12.
The conformation of dinonyl poly para phenylene ethynylenes (PPEs) with carboxylate side chains, equilibrated in solvents of different quality have been studied using molecular dynamics simulations. PPEs are of interest because of their tunable electro‐optical properties, chemical diversity, and functionality which are essential in wide range of applications. The polymer conformation determines the conjugation length and their assembly mode and affects electro‐optical properties which are critical in current and potential uses. This study investigates the effect of carboxylate fraction on PPEs side chains on the conformation of chains in the dilute limit, in solvents of different quality. The dinonyl PPE chains are modeled atomistically, where the solvents are modeled both implicitly and explicitly. Dinonyl PPEs maintained a stretched out conformation up to a carboxylate fraction f of 0.7 in all solvents studied. The nonyl side chains are extended and oriented away from the PPE backbone in toluene and in implicit good solvent, whereas in water and implicit poor solvent, the nonyl side chains are collapsed toward the PPE backbone. Rotation around the aromatic ring is fast and no long range correlations are seen within the backbone. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2016 , 54, 582–588  相似文献   

13.
A polyimide‐graft‐polystyrene (PI‐g‐PS) copolymer with a polyimide backbone and polystyrene side chains was synthesized by the “grafting from” method using styrene polymerization on a polyimide multicenter macroinitiator via ATRP mechanism. The side chain grafting density z = 0.86 of PI‐g‐PS is rather high for graft‐copolymers synthesized by the ATRP method. Molecular characteristics and solution behavior of PI‐g‐PS were studied in selective solvents using light scattering and viscometry methods. In all solvents, the backbone tends to avoid contact with a poor solvent. To describe the conformation and hydrodynamic properties of PI‐g‐PS macromolecules in thermodynamically good solvents for side chains and PI‐g‐PS, the wormlike spherocylinder model is used. Macromolecules of the studied graft‐copolymer are characterized by high equilibrium rigidities (Kuhn segment length >20 nm). In Θ‐conditions, PI‐g‐PS macromolecules may be modeled by a rigid prolate ellipsoid of revolution with a low asymmetry form and a collapsed backbone as the ellipsoid core. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1539–1546  相似文献   

14.
Covalent side‐chain cross‐links are a versatile method to control peptide folding, particularly when α‐helical secondary structure is the target. Here, we examine the application of oxime bridges, formed by the chemoselective reaction between aminooxy and aldehyde side chains, for the stabilization of a helical peptide involved in a protein–protein complex. A series of sequence variants of the dimeric coiled coil GCN4‐p1 bearing oxime bridges at solvent‐exposed positions were prepared and biophysically characterized. Triggered unmasking of a side‐chain aldehyde in situ and subsequent cyclization proceed rapidly and cleanly at pH 7 in the folded protein complex. Comparison of folding thermodynamics among a series of different oxime bridges show that the cross links are consistently stabilizing to the coiled coil, with the extent of stabilization sensitive to the exact size and structure of the macrocycle. X‐ray crystallographic analysis of a coiled coil with the best cross link in place and a second structure of its linear precursor show how the bridge is accommodated into an α‐helix. Preparation of a bicyclic oligomer by simultaneous formation of two linkages in situ demonstrates the potential use of triggered oxime formation to both trap and stabilize a particular peptide folded conformation in the bound state.  相似文献   

15.
Using simulation to study the folding kinetics of 20-mer poly-phenylacetylene (pPA) oligomers, we find a long time scale trapped kinetic phase in the cumulative folding time distribution. This is demonstrated using molecular dynamics to simulate an ensemble of over 100 folding trajectories. The simulation data are fit to a four-state kinetic model which includes the typical folded and unfolded states, along with an intermediate state, and most surprisingly, a kinetically trapped state. Topologically diverse conformations reminiscent of alpha helices, beta turns, and sheets in proteins are observed, along with unique structures in the form of knots. The nonhelical conformations are implicated, on the basis of structural correlations to kinetic parameters, to contribute to the trapped kinetic behavior. The strong solvophobic forces which mediate the folding process and produce a stable helical folded state also serve to overstabilize the nonhelical conformations, ultimately trapping them. From our simulations, the folding time is predicted to be on the order of 2.5-12.5 mus in the presence of the trapped kinetic phase. The folding mechanism for these 20-mer chains is compared with the previously reported folding mechanism for the pPA 12-mer chains. A linear scaling relationship between the chain length and the mean first passage time is predicted in the absence of the trapped kinetic phase. We discuss the major implications of this discovery in the design of self-assembling nanostructures.  相似文献   

16.
The development of peptidomimetic helical foldamers with a wide repertoire of functions is of significant interest. Herein, we report the X‐ray crystal structures of a series of homogeneous l ‐sulfono‐γ‐AA foldamers and elucidate their folding conformation at the atomic level. Single‐crystal X‐ray crystallography revealed that this class of oligomers fold into unprecedented dragon‐boat‐shaped and unexpected left‐handed helices, which are stabilized by the 14‐hydrogen‐bonding pattern present in all sequences. These l ‐sulfono‐γ‐AApeptides have a helical pitch of 5.1 Å and exactly four side chains per turn, and the side chains lie perfectly on top of each other along the helical axis. 2D NMR spectroscopy, computational simulations, and CD studies support the folding conformation in solution. Our results provide a structural basis at the atomic level for the design of novel biomimetics with a precise arrangement of functional groups in three dimensions.  相似文献   

17.
Optically active poly(m‐phenylene)s substituted with chiral oxazoline derivatives have been synthesized by the nickel‐catalyzed Yamamoto coupling reaction of optically active (S)‐4‐benzyl‐2‐(3,5‐dihalidephenyl)oxazoline derivatives (X = Br or I). The structures and chiroptical properties of the polymers were characterized by spectroscopic methods and thermal gravimetric analyses. The polymers showed higher absolute optical specific rotation values than their corresponding monomer, and showed a Cotton effect at transition region of conjugated main chain. The optical activities of the polymers should be attributed to the higher order structure such as helical conformations. Moreover, the helical conformation could be induced by addition of metal salts into polymer solutions. The polymers showed good thermal stabilities, which was attributable to the oxazoline side chains. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013  相似文献   

18.
The hydroxyl at the C-3 of cholic acid was converted to an amino group, and the resulting amino-functionalized cholic acid was used as a monomer to prepare amide-linked oligomeric cholates. These cholate oligomers fold into helical structures with nanometer-sized hydrophilic internal cavities in solvent mixtures consisting of mostly nonpolar solvents such as carbon tetrachloride or ethyl acetate/hexane and 2-5% of a polar solvent such as methanol or DMSO. The conformations of the foldamers were studied by UV, fluorescence, fluorescence quenching, and fluorescence resonance energy transfer. The nature of the polar/nonpolar solvents and their miscibility strongly influenced the folding reaction. Folding was cooperative, as evidenced by the sigmoidal curves in solvent denaturation experiments. The folded conformers became more stable with an increase in the chain length. The folding/unfolding equilibrium was highly sensitive toward the amount of polar solvent. One percent variation in the solvent composition could change the folding free energies by 0.5-1.4 kcal/mol.  相似文献   

19.
Polymer bottlebrushes with monodisperse oligoproline side chains were efficiently synthesized, and the conformation of the peptide side chains in different solvents was investigated. Polymers with number-average degrees of polymerization (DPn) of 89 and 366 were obtained by polymerization of the macromonomer in iPrOH/MeCN (1:1) and hexafluoroisopropanol, respectively. Circular dichroism (CD) spectra of the bottlebrush polymers in the neutral and charged states reveal that the oligoproline side chains attain stable polyproline II (PPII) helical conformations not only in aqueous solution, but also in aliphatic alcohol solutions. Dense attachment of oligopeptides onto a linear polymer chain did not lead to an increase in helix content. The possible effects of the main-chain length on the conformational stability were examined. The switching between the polyproline I (PPI) and PPII helical conformations for the oligoproline side chains in aliphatic alcohol solutions is believed to be inhibited by the overcrowded structure in the polymer bottlebrushes.  相似文献   

20.
Local energetic effects of amino acid replacements are often considered to have only a moderate influence on the backbone conformation of proteins or peptides. As these effects are difficult to determine experimentally, no comparison has yet been performed. However, knowledge of the influence of side chain mutations is essential in protein homology modeling and in optimizing biologically active peptide ligands in medicinal chemistry. Furthermore, the tool of N‐methylation of peptides is of increasing importance for the design of peptidic drugs to gain oral availability or receptor selectivity. However, N‐methylation is often accompanied by considerable population of cis‐peptide bond structures, resulting in completely different conformations compared with the parent peptide. To retain a favored structure, it might be important to understand the effect of different side chains on the backbone conformation and to enable the introduction of an N‐methylation at the right position without disturbing a biologically active conformation. In order to detect even small energetic effects due to side chain mutations, we employed a trick to investigate the structural equilibrium of a selected cyclic pentapeptide in which two conformations are equally populated. Very small energetic differences between both conformations could easily be determined experimentally by identifying shifts in the population of both isomers.  相似文献   

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