Showing papers on "Side chain published in 2001"
TL;DR: In this paper, a free-standing anisotropic side chain liquid crystalline elastomer films have been prepared using mesogens with laterally affixed polymerizable side chains and the calculated cross-linking density, as determined from the Young's modulus, was in the 10 -5 mol/cm3 range.
Abstract: Free-standing anisotropic side chain liquid crystalline elastomer films have been prepared using mesogens with laterally affixed polymerizable side chains. We present data on two networks: one containing the monomer of 4‘-acryloyloxybutyl 2,5-(4‘-butyloxybenzoyloxy)benzoate and another from a 50/50 mol % mixture of the above with 4‘-acryloyloxybutyl 2,5-di(4‘-pentylcyclohexyloyloxy)benzoate. The cross-linking was achieved using 10 mol % of 1,6-hexanediol diacrylate. The calculated cross-linking density, as determined from the Young's modulus, was in the 10 -5 mol/cm3 range. Thermoelastic responses show strain changes through the nematic−isotropic phase transition to be 30−45%. The order parameters of the oriented films were determined from the dichroic ratio of IR absorption at 3343 cm-1 to the in-plane aromatic stretching overtone of the LC mesogen core. The variation of the order parameter with temperature scales similar to the strain changes at constant stress. Isostrain studies, conducted through the...
600 citations
TL;DR: In this article, the molecular weights of the resulting polymers were characterized by gel permeation chromatography (GPC) using refractive index and multiangle light scattering detection, confirming the synthesis of well-defined copolymer brushes.
Abstract: Brush macromolecules having poly(n-butyl acrylate-block-styrene) and poly(styrene-block-n-butyl acrylate) side chains have been synthesized by the “grafting from” approach using atom transfer radical polymerization (ATRP). The molecular weights of the resulting polymers were characterized by gel permeation chromatography (GPC) using refractive index and multiangle light scattering detection. The block copolymer side chains were cleaved from the backbone and analyzed by GPC, confirming the synthesis of well-defined copolymer brushes. Visualization of individual molecules by atomic force microscopy (AFM) enabled analysis of the conformation and microstructure of the brush macromolecules on mica surface. The brushes with the pnBuA core were almost fully stretched, while the inverted structure with the pS core exhibited longitudinal contraction compared to the contour length of the main chain. In addition, the poly(n-butyl acrylate-block-styrene) brushes demonstrated a characteristic necklace morphology which...
372 citations
TL;DR: In this article, the minority charge carrying capacity of the homopolymers is probed: it is shown that the quinoxaline derivative has hole blocking properties superior to those of the oxadiazole polymer and is a good candidate for use in optimised devices.
Abstract: Improved syntheses and polymerisations are reported of monomers bearing electron transporting substituents based on 2,5-diphenyloxadiazole and 2,3-diphenylquinoxaline attached directly to a vinyl group. By copolymerisation and by use of mixtures of homopolymers, these materials have been incorporated into light emitting polymer devices in which hole conduction properties are provided by 4-vinyltriphenylamine groups. High luminescence efficiency is achieved by use of a fluorescent additive. The resulting devices show narrow emission bands and high brightnesses, except in the case of those based on a diphenyloxadiazole–triphenylamine polymer blend. Thermal analysis data are equivocal but we present evidence that in this system, but not the quinoxaline blend, phase separation occurs. The minority charge carrying capacity of the homopolymers is probed: it is shown that the quinoxaline derivative has hole blocking properties superior to those of the oxadiazole polymer and is
a good candidate for use in optimised devices.
339 citations
TL;DR: Expectations that receptor‐bound protein ligands and slightly larger proteins can be readily assigned in the near future by using three‐dimensional versions of the applied or analogous techniques are raised.
Abstract: The backbone and side-chain 13C and 15N signals of a solid 62-residue (u-13C,15N)-labelled protein containing the alpha-spectrin SH3 domain were assigned by two-dimensional (2D) magic angle spinning (MAS) 15N-13C and 13C-13C dipolar correlation spectroscopy at 17.6 T. The side-chain signal sets of the individual amino acids were identified by 2D 13C-13C proton-driven spin diffusion and dipolar recoupling experiments. Correlations to the respective backbone nitrogen signals were established by 2D NCACX (CX=any carbon atom) experiments, which contain a proton-nitrogen and a nitrogen-carbon cross-polarisation step followed by a carbon-carbon homonuclear transfer unit. Interresidue correlations leading to sequence-specific assignments were obtained from 2D NCOCX experiments. The assignment is nearly complete for the SH3 domain residues 7-61, while the signals of the N- and C-terminal residues 1-6 and 62, respectively, outside the domain boundaries are not detected in our MAS spectra. The resolution observed in these spectra raises expectations that receptor-bound protein ligands and slightly larger proteins (up to 20 kDa) can be readily assigned in the near future by using three-dimensional versions of the applied or analogous techniques.
304 citations
TL;DR: It is shown that many of the side chain amide groups of Asn and Gln residues in the C-terminal domain of the protein are affected by a chemical exchange process which may be important in facilitating the rapid binding of hydrophobic ligands to the cavity.
Abstract: A new NMR experiment is presented for the measurement of μs−ms time scale dynamics of Asn and Gln side chains in proteins. Exchange contributions to the 15N line widths of side chain residues are determined via a relaxation dispersion experiment in which the effective nitrogen transverse relaxation rate is measured as a function of the number of refocusing pulses in constant-time, variable spacing CPMG intervals. The evolution of magnetization from scalar couplings and dipole−dipole cross-correlations, which has limited studies of exchange in multi-spin systems in the past, does not affect the extraction of accurate exchange parameters from relaxation profiles of NH2 groups obtained in the present experiment. The utility of the method is demonstrated with an application to a Leu → Ala cavity mutant of T4 lysozyme, L99A. It is shown that many of the side chain amide groups of Asn and Gln residues in the C-terminal domain of the protein are affected by a chemical exchange process which may be important in f...
283 citations
TL;DR: In this paper, a series of soluble alternating polyfluorene copolymers with different main chain structures and those of the same main chain structure polyfluororene-co-alt-phenylene with different functional groups attached at the 2 and/or 5 positions of the phenylene ring were synthesized by a palladium-catalyzed Suzuki coupling reaction.
Abstract: A series of soluble alternating polyfluorene copolymers with different main chain structures and those of the same main chain structure polyfluorene-co-alt-phenylene with different functional groups attached at the 2- and/or 5-positions of the phenylene ring were synthesized by a palladium-catalyzed Suzuki coupling reaction. All 10 polymers had the band gaps ranging from 2.81 to 3.35 eV, corresponding to blue-light emission. Through controllable modification for both the main chain structures and the side chains, not only the optical and electronic properties of the blue emissive polymers had been tuned, but also the structure−property relationships, especially the HOMO and LUMO energy level engineering, had been studied. Relatively high PL efficiency in both solution and film states, good thermal stability, and relatively high glass transition temperatures were demonstrated on these polymers. In general, polymers with the main chain structure of polyfluorene-co-alt-phenylene were found to have higher Φfl...
273 citations
TL;DR: By properly adjusting the OXD content through copolymerization, this work can tailor the chemical structure of electroluminescent material to give a balance of hole- and electron injections for various metal cathodes, such that the quantum efficiency is significantly improved and the turn-on voltage is reduced for the devices with aluminum and calcium.
Abstract: We report a new route for the design of efficient soluble electroluminescent PPV-based copolymers bearing electron-deficient oxadiazole (OXD) moieties on side chains. The introduction of OXD through a long alkylene spacer with PPV backbone provides a molecular dispersion of OXD in the film; both the side chain OXD and the main chain PPV do retain their own electron-transport and emissive properties, respectively. The use of phenylene vinylene derivatives with asymmetric and branched substituents and a long spacer provides solubility for ease of device fabrication as well as amorphous structure to allow a well-mixing of OXD groups with the main chains. By properly adjusting the OXD content through copolymerization, we can tailor the chemical structure of electroluminescent material to give a balance of hole- and electron injections for various metal cathodes, such that the quantum efficiency is significantly improved and the turn-on voltage is reduced for the devices with aluminum and calcium. For the devi...
267 citations
TL;DR: The limits of side-chain prediction for core residues are extended, and the prediction of the conformation of a single side- Chain with all others fixed in their native conformations is only slightly more accurate than the simultaneous prediction of all side- chain dihedral angles.
260 citations
TL;DR: The saturated 4-substituted pyrrolidine nitroxides are shown to be a suitable template for novel "functionalized" side chains designed to mimic salient features of the native side chains they replace.
Abstract: Two single cysteine substitution mutants at helix surface sites in T4 lysozyme (D72C and V131C) have been modified with a series of nitroxide methanethiosulfonate reagents to investigate the structural and dynamical origins of their electron paramagnetic resonance spectra. The novel reagents include 4-substituted derivatives of either the pyrroline or pyrrolidine series of nitroxides. The spectral line shapes were analyzed as a function of side chain structure and temperature using a simulation method with a single order parameter and diffusion rates about three orthogonal axes as parameters. Taken together, the results provide strong support for an anisotropic motional model of the side chain, which was previously proposed from qualitative features of the spectra and crystal structures of spin labeled T4 lysozyme. Site-specific differences in apparent order parameter are interpreted in terms of backbone dynamics modes with characteristic correlation times in the nanosecond or faster time scale. The satur...
253 citations
TL;DR: The results suggest that methods developed for rigid lattice conditions can be used to analyze dipolar interactions between nitroxides even in the presence of motion of the individual spins, provided the rotational correlation time of the interspin vector is sufficiently long.
Abstract: Magnetic dipolar interactions between pairs of solvent-exposed nitroxide side chains separated by approximately one to four turns along an α-helix in T4 lysozyme are investigated. The interactions are analyzed both in frozen solution (rigid lattice conditions) and at room temperature as a function of solvent viscosity. At room temperature, a novel side chain with hindered internal motion is used, along with a more commonly employed nitroxide side chain. The results suggest that methods developed for rigid lattice conditions can be used to analyze dipolar interactions between nitroxides even in the presence of motion of the individual spins, provided the rotational correlation time of the interspin vector is sufficiently long. The distribution of distances observed for the various spin pairs is consistent with rotameric equilibria in the nitroxide side chain, as observed in crystal structures. The existence of such distance distributions places important constraints on the interpretation of internitroxide ...
229 citations
TL;DR: A self-consistent field lattice model of the interface between comb polymer films and water predicts an organization of the top molecular layer of comb polymer with the backbone oriented parallel to the interface in quasi-two-dimensional confinement and hydrophilic side chains extended in a brushlike layer into solution.
TL;DR: The results indicate that the equilibrium unfolded state of apomyoglobin formed at pH 2.3 is an excellent model for the events that are expected to occur in the earliest stages of protein folding, providing insights into the regions of the polypeptide that spontaneously undergo local hydrophobic collapse and sample nativelike secondary structure.
Abstract: Apomyoglobin forms a denatured state under low-salt conditions at pH 2.3. The conformational propensities and polypeptide backbone dynamics of this state have been characterized by NMR. Nearly complete backbone and some side chain resonance assignments have been obtained, using a triple-resonance assignment strategy tailored to low protein concentration (0.2 mM) and poor chemical shift dispersion. An estimate of the population and location of residual secondary structure has been made by examining deviations of (13)C(alpha), (13)CO, and (1)H(alpha) chemical shifts from random coil values, scalar (3)J(HN,H)(alpha) coupling constants and (1)H-(1)H NOEs. Chemical shifts constitute a highly reliable indicator of secondary structural preferences, provided the appropriate random coil chemical shift references are used, but in the case of acid-unfolded apomyoglobin, (3)J(HN,H)(alpha) coupling constants are poor diagnostics of secondary structure formation. Substantial populations of helical structure, in dynamic equilibrium with unfolded states, are formed in regions corresponding to the A and H helices of the folded protein. In addition, the deviation of the chemical shifts from random coil values indicates the presence of helical structure encompassing the D helix and extending into the first turn of the E helix. The polypeptide backbone dynamics of acid-unfolded apomyoglobin have been investigated using reduced spectral density function analysis of (15)N relaxation data. The spectral density J(omega(N)) is particularly sensitive to variations in backbone fluctuations on the picosecond to nanosecond time scale. The central region of the polypeptide spanning the C-terminal half of the E helix, the EF turn, and the F helix behaves as a free-flight random coil chain, but there is evidence from J(omega(N)) of restricted motions on the picosecond to nanosecond time scale in the A and H helix regions where there is a propensity to populate helical secondary structure in the acid-unfolded state. Backbone fluctuations are also restricted in parts of the B and G helices due to formation of local hydrophobic clusters. Regions of restricted backbone flexibility are generally associated with large buried surface area. A significant increase in J(0) is observed for the NH resonances of some residues located in the A and G helices of the folded protein and is associated with fluctuations on a microsecond to millisecond time scale that probably arise from transient contacts between these distant regions of the polypeptide chain. Our results indicate that the equilibrium unfolded state of apomyoglobin formed at pH 2.3 is an excellent model for the events that are expected to occur in the earliest stages of protein folding, providing insights into the regions of the polypeptide that spontaneously undergo local hydrophobic collapse and sample nativelike secondary structure.
TL;DR: The conformational structures of tryptophan, isolated in the gas phase, have been assigned by combining the results of ultraviolet hole-burning and infrared ion dip spectroscopy with the predictions of ab initio calculations conducted at the MP2/6-311 + G(d,p)//B3LYP/6 −31 + G (d) levels of theory as discussed by the authors.
Abstract: The conformational structures of tryptophan, isolated in the gas phase, have been assigned by combining
the results of ultraviolet hole-burning and infrared ion dip spectroscopy with the predictions of ab initio
calculations conducted at the MP2/6-311 + G(d,p)//B3LYP/6-31 + G(d) levels of theory. As in phenylalanine, the
most strongly populated, and lowest energy conformer presents a folded alanyl side chain that is stabilised by a ‘daisy chain’ of hydrogen-bonded interactions. These link the acidic proton, the amino group and the indole ring. There is a further interaction between the carbonyl oxygen and the neighbouring CH group on the pyrrole ring. A quantitative evaluation of the dipole–dipole interactions between the alanyl side chain and the indole ring in the 1La and 1Lb electronic states does not support the suggestion of electronic state mixing. In
particular it casts doubt on the assignment of the fluorescence of the most
stable, ‘special’ conformer to emission from the 1La state.
TL;DR: Chain length-related factors that stabilize organosoluble peptoid helices of this class are discussed, which are important for the design of helical, biomimetic peptoids sharing this structural motif.
Abstract: Oligomeric N-substituted glycines or “peptoids” with α-chiral, aromatic side chains can adopt stable helices in organic or aqueous solution, despite their lack of backbone chirality and their inability to form intrachain hydrogen bonds. Helical ordering appears to be stabilized by avoidance of steric clash as well as by electrostatic repulsion between backbone carbonyls and π clouds of aromatic rings in the side chains. Interestingly, these peptoid helices exhibit intense circular dichroism (CD) spectra that closely resemble those of peptide α-helices. Here, we have utilized CD to systematically study the effects of oligomer length, concentration, and temperature on the chiral secondary structure of organosoluble peptoid homooligomers ranging from 3 to 20 (R)-N-(1-phenylethyl)glycine (Nrpe) monomers in length. We find that a striking evolution in CD spectral features occurs for Nrpe oligomers between 4 and 12 residues in length, which we attribute to a chain length-dependent population of alternate struct...
TL;DR: In protein NMR relaxation data, changes in flexibility that occur upon ligand binding, mutation, or changes in sample conditions can be interpreted in terms of contributions to conformational entropy as mentioned in this paper.
Abstract: Recent advances in the measurement and analysis of protein NMR relaxation data have made it possible to characterize the dynamical properties of many backbone and side chain groups. With certain caveats, changes in flexibility that occur upon ligand binding, mutation, or changes in sample conditions can be interpreted in terms of contributions to conformational entropy. Backbone and side chain flexibility can either decrease or increase upon ligand binding. Decreases are often associated with “enthalpy−entropy compensation” and “induced fit” binding, whereas increases in conformational entropy can contribute to stabilization of complexes. In certain cases, conformational entropy appears to play a role in cooperative binding and enzyme catalysis. In addition, variations in conformational entropy and heat capacity may both be important in stabilizing the folded structures of proteins.
TL;DR: The synthesis of shape-persistent macrocycles based on the phenyl-ethynyl backbone containing various extraannular alkyl side chains is described, supporting the model of a solvophobic effect.
Abstract: The synthesis of shape-persistent macrocycles based on the phenyl-ethynyl backbone containing various extraannular alkyl side chains is described. Although compound solubility increases with increa...
TL;DR: Results show that prior to rubbing the surface, both the pendent cyanobiphenyls in the side chains and backbones possess nearly planar chain conformations at the polyimide surface, and the polar cyano groups point down toward the layer surface deduced from SHG phase measurements.
Abstract: Surface lamellar decoration (SLD), surface enhanced Raman scattering (SERS) and optical second harmonic generation (SHG) experiments have been utilized to study the molecular orientation and conformation changes at a rubbed polyimide alignment-layer surface. This aromatic polyimide containing pendent cyanobiphenyl mesogens was synthesized via a polycondensation of 2,2'-bis(3,4-dicarboxy-phenyl)hexafluoropropane dianhydride (6FDA) with bis[omega-[4-(4-cyanophenyl)phenoxy]hexyl] 4,4'-diamino-2,2'-biphenyldicarboxylate (nCBBP, n = 6), abbreviated as 6FDA--6CBBP. Uniform alignment layers, possessing high pretilt angles ranging from 39 degrees to 43 degrees, have been achieved after mechanical rubbing of the polyimide thin film surface at room temperature and subsequent annealing. This is the first time that high pretilt angles have been detected to possess a negative angle (-theta(c)) with respect to the rubbing direction (i.e., opposite to the rubbing direction), considerably different from the conventional pretilt angle (theta(c)) observed along the rubbing direction. This observation is confirmed using magnetic null and SHG methods. Combined polyethylene (PE) SLD and atomic force microscopy experiments reveal that the azimuthal orientation distribution of the long axis of the edge-on PE lamellar crystals is oriented normal to the rubbing direction, indicating that the PE chains are aligned parallel to the rubbing direction. This SLD technique probes the anisotropic surface orientation of the outermost molecules of the rubbed polyimide layer. The SERS results show that prior to rubbing the surface, both the pendent cyanobiphenyls in the side chains and backbones possess nearly planar chain conformations at the polyimide surface. Mechanical rubbing causes not only tilting of the backbone moieties, such as imide-phenylene structure, but also significant conformational rearrangements of the pendent side chains at the surfaces. The molecular mechanism of this unusual alignment is due to the fact that the pendent cyanobiphenyls forms a uniformly tilted conformation on the rubbed surface, and the polar cyano groups point down toward the layer surface deduced from SHG phase measurements. This conformational rearrangement of the side chains results in the formation of fold-like bent structures on the surface, which directly leads to the long axis of cyanobiphenyls having the -theta(c) pretilt angle with respect to the rubbing direction.
TL;DR: In this article, microcalorimetric measurements have been made on the series of gemini surfactants [CMH2M+1(CH3)2N(CH2)SN(CH 3)2CMH 2M +1] Br2, designated CMCSCMBr2, where M and S indicate the numbers of carbons in the side chains and spacer respectively, for M = 12 and S = 3, 4, 6, 8, 10, 12.
Abstract: Microcalorimetric measurements have been made on the series of gemini surfactants [CMH2M+1(CH3)2N(CH2)SN(CH3)2CMH2M+1] Br2, designated CMCSCMBr2, where M and S indicate the numbers of carbons in the side chains and spacer respectively, for M = 12 and S = 3, 4, 6, 8, 10, 12. For comparison, parallel measurements have been made on the series of double-chain, singly charged surfactants dodecyldimethylalkylammonium bromides, designated as C12CNBr with N = 1, 2, 4, 6, 8, 10, 12, where N is the number of carbons in the secondary alkyl chain. The choice of this second series was to compare each CMCSCMBr2 with its nearest equivalent monomer C12CS/2Br. The values of the critical micelle concentrations (cmc) were found to be in good agreement with other measurements, showing a maximum at S = 4−6 for the geminis and a nonlinear variation with chain length for the C12CNBr series. For both series of surfactants, the enthalpies of micellization, ΔHmic, are all exothermic and show a marked minimum in magnitude at S = 4−...
TL;DR: The 5-CH and the 7-Me responses are doubled, which provides evidence for the existence of at least two relatively well-defined structurally different arrangements, and the analogy between aggregation shifts for BChl c in the chlorosome and for self-assembled chlorophyll a/H(2)O is explored.
Abstract: Heteronuclear 2-D and 3-D magic-angle spinning NMR dipolar correlation spectroscopy was applied to determine solid-state 1H shifts for aggregated bacteriochlorophyll c (BChl c) in uniformly 13C-enriched light harvesting chlorosomes of the green photosynthetic bacterium Chlorobium tepidum. A complete assignment of 29 different observable resonances of the 61 protons of the aggregated BChl c in the intact chlorosomes is obtained. Aggregation shifts relative to monomeric BChl c in solution are detected for protons attached to rings I, II, and III/V and to their side chains. The 21-H3, 32-H3, and 31-H resonances are shifted upfield by −2.2, −1, and −3.3 ppm, respectively, relative to monomeric BChl c in solution. Although the resonances are inhomogeneously broadened and reveal considerable global structural heterogeneity, the 5-CH and the 7-Me responses are doubled, which provides evidence for the existence of at least two relatively well-defined structurally different arrangements. Ab initio quantum chemical...
TL;DR: The contributions of interstrand side chain-side chain contacts to beta-sheet stability have been examined with an autonomously folding beta-hairpin model system, and the conformational impact of the mutations is assessed.
Abstract: The contributions of interstrand side chain−side chain contacts to β-sheet stability have been examined with an autonomously folding β-hairpin model system. RYVEVDPGOKILQ-NH2 (DP = d-proline, O = ornithine) has previously been shown to adopt a β-hairpin conformation in aqueous solution, with a two-residue loop at d-Pro-Gly. In the present study, side chains that display interstrand NOEs (Tyr-2, Lys-9, and Leu-11) are mutated to alanine or serine, and the conformational impact of the mutations is assessed. In the β-hairpin conformation Tyr-2 and Leu-11 are directly across from one another (non-hydrogen bonded pair). This “lateral” juxtaposition of two hydrophobic side chains appears to contribute to β-hairpin conformational stability, which is consistent with results from other β-sheet model studies and with statistical analyses of interstrand residue contacts in protein crystal structures. Interaction between the side chains of Tyr-2 and Lys-9 also stabilizes the β-hairpin conformation. Tyr-2/Lys-9 is a “...
TL;DR: In this paper, a nematic liquid crystal in contact with a layer of a model coumarin side chain polymer is obtained with the director parallel or perpendicular to the UV polarization axis depending on the incident fluence.
Abstract: A surface anisotropy has been shown previously to be induced in thin films of photoreactive coumarin side-chain polymers by polarized UV illumination. Consequently, the resultant cross-linked polymer layers can be used as photoalignment layers for liquid crystal displays. Homogeneous alignment of a nematic liquid crystal in contact with a layer of a model coumarin side chain polymer is obtained with the director parallel or perpendicular to the UV polarization axis depending on the incident fluence. Spectroscopic analysis of the alignment layer now confirms that both photodegradation and cross-linking occur with different dependencies on fluence. Low UV fluences give parallel photoalignment and high cross-linking reactivity. However, the residual, unreacted polymer side chains show negligible anisotropy because of their freedom to move in an isotropic fashion. Hence, parallel liquid crystal alignment is attributed to a steric interaction between the liquid crystal and syn-dimerized side chains of the cros...
TL;DR: These results provide the first rationale for the particular rate enhancement of degradation in peptidyl Asn-/Asp-Gly sequences and find that the acidity of the backbone peptide nitrogen NH is highly dependent upon the conformation of the molecule.
Abstract: The rate of spontaneous degradations of asparagine and aspartyl residues occurring through succinimide intermediates is dependent upon the nature of the residue on the carboxyl side in peptides. For nonglycine residues, we show here that this effect can largely be attributed to the electrostatic/inductive effect of the side chain group on the equilibrium concentration of the anionic form of the peptide bond nitrogen atom that initiates the succinimide forming reaction. However, the rate of degradation of Asn-Gly and Asp-Gly containing peptides is about an order of magnitude greater than predicted solely using this explanation. To understand the nature of the glycine effect, ab initio calculations were performed on model compounds. These calculations indicate that there is little to no change in the stability of the transition state or the tetrahedral intermediate of succinimide formation with Asn-/Asp-Gly and Asn-/Asp-Ala derivatives. However, we have found that the acidity of the backbone peptide nitrogen NH is highly dependent upon the conformation of the molecule. Since glycine residues lack the beta-carbon common to all other protein amino acids, these residues can sample additional regions of conformational space where it is possible to further stabilize the backbone amide anion and thus increase the rate of degradation. These results provide the first rationale for the particular rate enhancement of degradation in peptidyl Asn-/Asp-Gly sequences. The results also can be applied to asparagine and aspartyl residues in proteins where the 3-dimensional structure provides additional constraints on conformation that can either increase or decrease the equilibrium concentration of the backbone amide anion and thus their rate of degradation via succinimide intermediates. Understanding this chemistry will assist attempts to minimize the deleterious effect of aging at the molecular level. The relationship between these results and proton exchange experiments is discussed in the Appendix.
TL;DR: The potential of the 19F nucleus to describe suitably labelled polypeptides in membranes, requiring only little material and short NMR acquisition times is demonstrated.
Abstract: The antimicrobial properties of the cyclic beta-sheet peptide gramicidin S are attributed to its destabilizing effect on lipid membranes. Here we present the membrane-bound structure and alignment of a derivative of this peptide, based on angular and distance constraints. Solid-state 19F-NMR was used to study a 19F-labelled gramicidin S analogue in dimyristoylphosphatidylcholine bilayers at a lipid:peptide ratio of 80:1 and above. Two equivalent leucine side chains were replaced by the non-natural amino acid 4F-phenylglycine, which serves as a highly sensitive reporter on the structure and dynamics of the peptide backbone. Using a modified CPMG multipulse sequence, the distance between the two 19F-labels was measured from their homonuclear dipolar coupling as 6 A. in good agreement with the known backbone structure of natural gramicidin S in solution. By analyzing the anisotropic chemical shift of the 19F-labels in macroscopically oriented membrane samples, we determined the alignment of the peptide in the bilayer and described its temperature-dependent mobility. In the gel phase, the 19F-labelled gramicidin S is aligned symmetrically with respect to the membrane normal, i.e., with its cyclic beta-sheet backbone lying flat in the plane of the bilayer, which is fully consistent with its amphiphilic character. Upon raising the temperature to the liquid crystalline state, a considerable narrowing of the 19F-NMR chemical shift dispersion is observed, which is attributed the onset of global rotation of the peptide and further wobbling motions. This study demonstrates the potential of the 19F nucleus to describe suitably labelled polypeptides in membranes, requiring only little material and short NMR acquisition times.
TL;DR: Molecular-dynamics simulations of the pentapeptide pairs confirmed that their association is dynamic and showed that cation-pi contacts between the two peptides are stereochemically possible.
Abstract: Cation-pi interactions between amino acid side chains are increasingly being recognized as important structural and functional features of proteins and other biomolecules. Although these interactions have been found in static protein structures, they have not yet been detected in dynamic biomolecular systems. We determined, by (1)H NMR spectroscopic titrations, the energies of cation-pi interactions of the amino acid derivative AcLysOMe (1) with AcPheOEt (2) and with AcTyrOEt (3) in aqueous and three organic solvents. The interaction energy is substantial; it ranges from -2.1 to -3.4 kcal/mol and depends only slightly on the dielectric constant of the solvent. To assess the effects of auxiliary interactions and structural preorganization on formation of cation-pi interactions, we studied these interactions in the association of pentapeptides. Upon binding of the positively-charged peptide AcLysLysLysLysLysNH(2) (5) to the negatively-charged partner AcAspAspXAspAspNH(2) (6), in which X is Leu (6a), Tyr (6b), and Phe (6c), multiple interactions occur. Association of the two pentapeptides is dynamic. Free peptides and their complex are in fast exchange on the NMR time-scale, and 2D (1)H ROESY spectra of the complex of the two pentapeptides do not show intermolecular ROESY peaks. Perturbations of the chemical shifts indicated that the aromatic groups in peptides 6b and 6c were affected by the association with 5. The association constants K(A) for 5 with 6a and with 6b are nearly equal, (4.0 +/- 0.7) x 10(3) and (5.0 +/- 1.0) x 10(3) M(-)(1), respectively, while K(A) for 5 with 6c is larger, (8.3 +/- 1.3) x 10(3) M(-)(1). Molecular-dynamics (MD) simulations of the pentapeptide pairs confirmed that their association is dynamic and showed that cation-pi contacts between the two peptides are stereochemically possible. A transient complex between 5 and 6 with a prominent cation-pi interaction, obtained from MD simulations, was used as a template to design cyclic peptides C(X) featuring persistent cation-pi interactions. The cyclic peptide C(X) had a sequence in which X is Tyr, Phe, and Leu. The first two peptides do, but the third does not, contain the aromatic residue capable of interacting with a cationic Lys residue. This covalent construct offered conformational stability over the noncovalent complexes and allowed thorough studies by 2D NMR spectroscopy. Multiple conformations of the cyclic peptides C(Tyr) and C(Phe) are in slow exchange on the NMR time-scale. In one of these conformations, cation-pi interaction between Lys3 and Tyr9/Phe9 is clearly evident. Multiple NOEs between the side chains of residues 3 and 9 are observed; chemical-shift changes are consistent with the placement of the side chain of Lys3 over the aromatic ring. In contrast, the cyclic peptide C(Leu) showed no evidence for close approach of the side chains of Lys3 and Leu9. The cation-pi interaction persists in both DMSO and aqueous solvents. When the disulfide bond in the cyclic peptide C(Phe) was removed, the cation-pi interaction in the acyclic peptide AC(Phe) remained. To test the reliability of the pK(a) criterion for the existence of cation-pi interactions, we determined residue-specific pK(a) values of all four Lys side chains in all three cyclic peptides C(X). While NOE cross-peaks and perturbations of the chemical shifts clearly show the existence of the cation-pi interaction, pK(a) values of Lys3 in C(Tyr) and in C(Phe) differ only marginally from those values of other lysines in these dynamic peptides. Our experimental results with dynamic peptide systems highlight the role of cation-pi interactions in both intermolecular recognition at the protein-protein interface and intramolecular processes such as protein folding.
TL;DR: It is shown here that the parallel or perpendicular orientation of the mesogens with respect to the main chain can be reversed by the application of an external field produced by a shear flow, demonstrating the existence of an isotropic nematic phase transition in SCLCPs.
Abstract: Flow-induced phase transitions are a fundamental (but poorly understood) property of non-equilibrium systems, and are also of practical importance for tuning the processing conditions for plastics, petroleum products, and other related materials21. Recognition that polymers may exhibit liquid crystal properties has led to the discovery of the first tailored side-chain liquid crystal polymers (SCLCPs), which are formed by inserting a spacer between the main polymer chain and the lateral mesogen liquid–crystalline graftings22. Subsequent research has sought to understand the nature of the coupling between the main polymer chain and the mesogens, with a view to obtaining better control of the properties of these tailored structures22. We show here that the parallel or perpendicular orientation of the mesogens with respect to the main chain can be reversed by the application of an external field produced by a shear flow, demonstrating the existence of an isotropic nematic phase transition in SCLCPs. Such a transition, which was theoretically predicted1,2 for low-molecular-weight liquid crystals but never observed, is shown to be a general property of SCLCPs too. We expect that these SCLCPs will prove to be good candidate systems for the experimental study of these non-equilibrium phenomena.
TL;DR: In this paper, a series of 3-substituted β-carboline derivatives was synthesized from l -tryptophan and the effects of the flexible alkylamine side chain on the intercalating ability and their antitumor activity were studied.
TL;DR: In this paper, the tandem mass spectrometry fragmentation reactions of 21 protonated N-acyl amino acid methyl esters are examined as models for more complicated peptides.
TL;DR: In this paper, the role played by the spacer group located in the side chain between the backbone and the fluorinated segment was investigated for poly[2-[[[[2-(perfluoroalkyl)ethyl]sulfonyl]methyl]amino]ethyl]acrylates (pASn).
Abstract: The organization of liquid crystalline fluorinated acrylate polymers has been generally described so far in the literature in terms of phase segregation between hydrogenated and fluorinated moieties within the polymer and preferential orientation induced by the backbone. However, little is known on the effects of the chemical composition on the properties of such fluorine-containing polymers. Our study was then focused on the role played by the spacer group located in the side chain between the backbone and the fluorinated segment and, in particular, on the properties of poly[2-[[[[2-(perfluoroalkyl)ethyl]sulfonyl]methyl]amino]ethyl]acrylates (pASn). Surface and bulk organization of fluorinated side chains of those polymers were investigated by surface tension, X-ray scattering, and differential scanning calorimetry measurements. Results were compared with those obtained with poly[(perfluoroalkyl)ethyl] acrylates (pAFn) of the same perfluoroalkyl chain lengths. A strong correlation between bulk organizati...
TL;DR: The 'Sergeants-and-Soldiers' principle has been examined in a series of m-phenylene ethynylene oligomers containing both chiral and achiral side chains, indicating that in acetonitrile a full bias of the helicity cannot be accomplished by chiral side Chains alone.
Abstract: The 'Sergeants-and-Soldiers' principle has been examined in a series of m-phenylene ethynylene oligomers containing both chiral and achiral side chains. Circular dichroism (CD) spectroscopy was used to examine the twist sense bias of the helical conformation in the polar solvent acetonitrile. A non-linear dependence of the CD signal on the amount of chiral side chains was observed revealing cooperative interactions among the side chains through the backbone. On the other hand, the experiments indicate that in acetonitrile a full bias of the helicity cannot be accomplished by chiral side chains alone. Nevertheless, the folded oligomers are highly ordered since the placement of a single chiral side chain at the beginning of an oligomer results in the induction of a strong twist sense bias into the ordered helical conformation.
TL;DR: A series of soluble hexabenzocoronene derivatives with pendant optically active hydrocarbon side chains with and without a phenylene spacer were assembled into differently ordered arrays at the interface between a solution and the basal plane of highly oriented pyrolytic graphite.
Abstract: A series of soluble hexabenzocoronene (HBC) derivatives with pendant optically active (S)-3,7-dimethyloctanyl and (R,S)-3,7-dimethyloctanyl (mixture of stereoisomers) hydrocarbon side chains with and without a phenylene spacer were assembled into differently ordered arrays at the interface between a solution and the basal plane of highly oriented pyrolytic graphite (HOPG). Molecularly resolved scanning tunneling microscopy (STM) images revealed that all derivatives self-assemble into oriented crystals in quasi-two dimensions. However, while for the alkyl-substituted HBCs (1,4) all of the single aromatic cores within a monolayer exhibit the same contrast in the STM, the single aromatic cores with a phenylene group between the alkyl side chains and the aromatic core (2a,2b,3) exhibit different contrasts within a monolayer. For the disks carrying racemic branched or n-alkyl side chains (2b,3) a random distribution of the two different contrasts within the 2D-crystal is observed, while the optically active ph...