Secondary structure formation in model polypeptide chains

Model polypeptide chains were folded into 3-D compact conformationsusing distance geometry techniques. Interresidue distances werepredicted from the hydrophobicity of the monomers and wererefined by repeated projections into lower-dimensional spaces.Main-chain hydrogen bond networks were constructed and propagatedthrough the structure by adjusting local conformations to complywith ideal distance constraints around hydrogen bonds. The resultingfolds were compact globules with distinct hydrophobic coresand contained secondary structure elements like real proteinmolecules. Apart from similarity in appearance, several propertiesof the model chains were also very close to those of nativefolded polypeptides. The method in its present form can serveas a starting point for the development of a novel structureprediction algorithm     

Shape memory properties of polypeptide hydrogels having hydrophobic alkyl side chains

Polypeptide hydrogels were prepared by cross-linking of hydrophobically-modified poly[N⁵-(2-hydroxyethyl) l-glutamine] having alkyl side chains –C_nH_2n+1. Chain length of the alkyl group was n = 8, 16, and 18, and their mole fractions in the polypeptide were varied in the range of 0.05–0.16. Shape memory ability of the prepared polypeptide hydrogels was investigated. After deformation at 60 °C, the hydrogel was cooled in order to fix the temporary deformed shape. It was found that crystallization of the alkyl side chains did not occur, and the fixation ability of the hydrogel at 0 °C was low. In the subsequent heating process, the deformed temporary shape spontaneously recovered to the original shape gradually with increasing temperature, in other words, the shape recovery ratio varied with depending on the recovery temperature. From these observations, it was proposed that the shape fixation of the polypeptide hydrogel was achieved by strong segregation of the hydrophobic alkyl chains at low temperature, and the shape recovery of the deformed hydrogel was accompanied by the gradual decrease of the segregation strength with the temperature increase.     

Block copolymers with a polyvinyl and a polypeptide block: factors governing the folding of the polypeptide chains

AB block copolymers polystyrene-poly(γ-benzyl-l-glutamate) (SG) of various molecular weights and compositions were synthesized and studied by X-ray diffraction and infra-red spectroscopy. They exhibit lamellar mesophases in the solid state and in dioxane concentrated solution. Each sheet of the lamellar structure results from the superposition of two layers: one formed by the polyvinyl chains in a disordered conformation, the other formed by the polypeptide chains in an α-helix conformation arranged in a hexagonal array and generally folded. The comparison of the lamellar structure of copolymers polystyrene-poly(γ-benzyl-l-glutamate) (SG), polybutadiene-poly(γ-benzyl-l-glutamate) (BG) and polystyrene-poly(ε-carbobenzoxy-l-lysine) (SCK) showed that: (1) for the three types of copolymers (copolymers SG or BG or SCK) the number of folds of the polypeptide chains increases with the molecular weight of both the polyvinyl and the polypeptide blocks; (2) for copolymers of fixed molecular weight of the polyvinyl block and fixed degree of polymerization of the polypeptide block the number of folds of the polypeptide chains depends upon the nature of both the polyvinyl and the polypeptide blocks: a polypeptide chain is more folded when it is linked to a polystyrene chain than to a polybutadiene chain but a poly(ε-carbobenzoxy-l-lysine) chain is more rigid than a poly(γ-benzyl-l-glutamate) chain.     

Preparation of cellulose graft copolymers having polypeptide side chains and their blood compatibility

Blood compatibility of cellulose graft copolymers with poly(γ-benzyl-L -glutamate) and poly(N⁵-2-hydroxyethyl-L -glutamine) (Cell-g-PBLG and Cell-g-PHEG) was examined in vivo blood tests. For this purpose, Cell-g-PBLG graft copolymers with PBLG contents ranging from 7 to 60 mol % were prepared by polymerizing N-carboxy-γ-benzyl-L-glutamate(γ-BLG NCA) using aminoethyl cellulose (AE-Cell) with degree of substitution of 0.05 as macroinitiator. Graft copolymerization was carried out under a variety of conditions at 20°C in dimethyl-sulfoxide. Monomer conversion higher than 60% were obtained for all the polymerization runs. The solubility tests revealed that all of the AE-Cell and the polypeptides formed were grafted. The Cell-g-PHEG graft copolymers were prepared by treating Cell-g-PBLG graft copolymers with 2-amino-1-ethanol. Characterization of these graft copolymers were carried out by IR spectroscopy, DSC, and water content measurement. Tests for blood compatibility, in vivo, were made by a method of peripheral vein indwelling suture which was developed by one of the authors. The coating of graft copolymers on the polyester suture was made by casting either from formic acid solution of LiCl/dimethylacetamide solutions using water as the regenerating medium, and the polymer-coated sutures were implanted into a jugular and femoral vein of a dog. The results showed that the graft copolymers examined have excellent antithrombogenic properties.     

Structure of AB block copolymers with a polypeptide block: Effect of the chain conformation

The structure of AB copolymers with a polypeptide block has been studied by X-ray diffraction, electron microscopy, infrared spectroscopy, and circular dichroism. Copolymers with a polyvinyl block (polybutadiene or polystyrene) and a hydrophobic polypeptide block (polybenzyl-L-glutamate or polycarbobenzoxy-L-lysine) exhibit a lamellar structure in the dry state and in solution in dioxane or in different chlorinated solvents. This lamellar structure consists of plane, parallel, equidistant sheets. Each sheet results from the superposition of two layers: one formed by the polyvinyl chains in amore or less random coil conformation, the other formed by the polypeptide chains in an α-helix conformation, arranged in a hexagonal array and generally folded. Copolymers with a polyvinyl block and a hydrophilic polypeptide block (poly-Llysine or poly-L-glutamic acid) exhibit a larnellar structure in water solution and in the dry state. The difference between this lamellar structure and the preceding one consists in the conformation of the polypeptide chains: an intramolecular mixture of coiled chains, α-helices, and β chains. Copolymers with a polysaccharide block and a hydrophobic polypeptide block exhibit in DMSO solution and in the dry state a lamellar structure similar to that of copolymers with a polyvinyl block and a hydrophobic polypeptide block.     

Enhanced dead-end elimination in the search for the global minimum energy conformation of a collection of protein side chains

Although the conformational states of protein side chains canbe described using a library of rotamers, the determinationof the global minimum energy conformation (GMEC) of a largecollection of side chains, given fixed backbone coordinates,represents a challenging combinatorial problem with importantapplications in the field of homology modelling. Recently, wehave developed a theoretical framework, called the dead-endelimination method, which allows us to identify efficientlyrotamers that cannot be members of the GMEC. Such dead-endingrotamers can be iteratively removed from the system under studythereby tracking down the size of the combinatorial problem.Here we present new developments to the dead-end eliminationmethod that allow us to handle larger proteins and more extensiverotamer libraries. These developments encompass (i) a procedureto determine weight factors in the generalized dead-end eliminationtheorem thereby enhancing the elimination of dead-ending rotamersand (ii) a novel strategy, mainly based on logical argumentsderived from the logic pairs theorem, to use dead-ending rotamerpairs in the efficient elimination of single rotamers. Thesedevelopments are illustrated for proteins of various sizes andthe flow of the current method is discussed in detail. The effectivenessof dead-end elimination is increased by two orders of magnitudeas compared with previous work. In addition, it now becomesfeasible to use extremely detailed libraries. We also providean appendix in which the validity of the generalized dead-endcriterion is shown. Finally, perspectives for further applicationswhich may now become within reach are discussed.     

Photoresponsive peptide and polypeptide systems: part II. Photochromism of poly(l-ornithine) containing various azo-contents in side chains

Poly(L-ornithine)s having various azo-contents in the side chains were synthesized by the water-soluble carbodiimide procedure. The photochemical properties of the polypeptides poly[N^δ-p-(phenylazo)benzoyl-L-ornithine] (PPABLO) containing 3–77 mol% azobenzene were investigated by absorption and circular dichroism spectroscopy in hexafluoro-2-propanol (HFIP) or water, and in HFIP-water or methanol-water solvent mixtures. The photochromism of the dichroic bands of the PPABLOs containing 20–77 mol% azobenzene in the visible and ultraviolet wavelength regions was found to be mostly reversible as a function of irradiation time at different wavelengths due to the photostationary state (above 80% trans-cis photoisomerization) of the azo aromatic moieties. The PPABLO containing 3.2 mol% azobenzene in water exhibited conformational changes from random coil to helix by the addition of methanol or sodium dodecyl sulphate (SDS). The photo-induced conformational change was observed in HFIP-water-SDS solvent mixtures, while no conformational change was seen in water and HFIP-water solvent mixtures.     

Study of three-dimensional polystyrene networks containing linear chains: 1. Influence of free chains on the volume fraction of crosslinked chains

A ternary system, crosslinked polystyrene-linear polystyrene in swelling equilibrium in benzene or cyclohexane, has been prepared by anionic polymerization in dilute solution (7.5%). By swelling ratios and modulus measurements we proposed to show the specific influence of linear polystyrene chains of high molecular weight, maintained inside the network, and to compare this behaviour with the behaviour of an ‘ideal’ polystyrene network. It may be concluded that: (i) the calculated number of elastic chains is independent of the swelling solvent, but the presence of free chains in the polymerization and crosslinking process produces a non-negligible number of free and pendant chains; (ii) for the same number of elastic chains, the two types of networks have the same swelling ratio, but the introduction of free chains into the networks leads to a decrease in the volume fraction of crosslinked chains, and thus to an increase in the swelling rate of the network. However, these values are consistent with the Gaussian theory; (iii) the values of functionality are lower than those found for ‘ideal’ networks; this result confirms the presence of pendant chains; (iv) the Flory-Huggins parameters are the same for the two types of networks.     

Vapor-assisted imprinting to pattern poly(3-hexylthiophene) (P3HT) film with oriented arrangement of nanofibrils and flat-on conformation of P3HT chains

Poly(3-hexylthiophene) (P3HT) film with a hierarchical ordered structure was fabricated by an approach combining vapor-assisted imprinting in a carbon disulfide (CS₂) atmosphere and thermal annealing treatment. In the hierarchical ordered structure, P3HT domains are vertically arranged and the domains are constituted by uniaxially aligned P3HT nanofibrils, furthermore, the chains in it adopted flat-on conformation. The vertically arranged domains are formed by the action of capillarity, the oriented nanofibrils are induced by the crystallization nucleation of P3HT and the directional evaporation of the solvent, and the flat-on conformation of P3HT chains are induced by the enhanced intermolecular interaction of the alkyl side chains in CS₂ atmosphere. The arrangement behavior of P3HT crystals and chains facilitate the bridging chains link neighboring grains with minimal distortion, while the enhanced intermolecular interaction enable the formation of larger P3HT crystals, and then reduce the quantity of grain boundary. As a result, this ordered structure provides more delocalized electrons along the direction that perpendicular to the substrate, which would result in an improvement of the carrier mobility along this direction.     

Twist-boat conformation in graphene oxides

We have investigated the structural, electronic, and vibrational properties of graphene oxide based on first-principles density-functional calculations. A twist-boat conformation is identified as the energetically most favorable nonmetallic configuration for fully oxidized graphene. The calculated Raman G-band blue shift is in very good agreement with experimental observations. Our results provide important insight into structural and electronic characteristics that are useful for further development of graphene-based nanodevices.     

Polymeric micelles formed by polypeptide graft copolymer and its mixtures with polypeptide block copolymer

Polymeric micelles based on poly(γ-benzyl-l-glutamate)-poly(ethylene glycol) graft copolymer (PBLG-g-PEG) with various degrees of grafting and the mixtures composed of PBLG-g-PEG and poly(γ-benzyl-l-glutamate)-poly(ethylene glycol) block copolymer (PBLG-b-PEG) were prepared by the dialysis method in deionized water. Fluorescence spectroscopy and transmission electron microscope (TEM) have been used to study the self-assembly behavior. The experimental results revealed that the degree of grafting exerts marked effect on the critical micelle concentration (CMC) and the morphology of the micelle formed by PBLG-g-PEG. With increasing the degree of grafting, the CMC value becomes larger and the morphology of formed micelle changes from irregular shape to spindle. It was also found that mixtures of PBLG-g-PEG/PBLG-b-PEG can associate into hybrid polymeric micelle with various shapes.     

pH-responsive release from polypeptide microcapsules

Microcapsules were prepared from [Glu(OMe)]_m(Sar)_n (m = 21, n = 19) and [Lys(Z)]_m(Sar)_n (m = 27, n = 15), and were chemically modified to obtain a pH-responsive releasing membranes. One membrane was prepared by partially deprotecting the ester groups of [Glu(OMe)]_m(Sar)_n. The other membrane was prepared by connecting of poly(Glu) to side chain amino groups that were generated by a partial deprotection of [Lys(Z)]_m (Sar)_n. Consequently, two types of polypeptidic microcapsules were prepared; Glu residues in the main chain, and Glu residues in the graft chains on the positively charged main chain. Both microcapsules showed pH-responsive release of FITC-dextran encapsulated in the microcapsules. The release rate became slower in the medium at pH 3.0 than pH 7.5. Optical microscope observation revealed that partially deblocked [Glu(OMe)]_m(Sar)_n microcapsules swelled more at pH 7.5 than at pH 3.0; hence, enhanced permeation through the polypeptide membrane at pH 7.5. However, the shape of poly(Glu)-grafted [Lys(Z)]_m(Sar)_n microcapsules changed a little by changing pH of the medium. It is suggested that ion-pairing between carboxylate groups of poly(Glu) and ammonium groups of Lys acts as crosslinking to give the shape stability. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 63: 453–458, 1997     

Substituted poly(silylenemethylene)s with short range interactions that induce a preference for the same local conformation in unperturbed atactic, isotactic, and syndiotactic chains

A rotational isomeric state model has been developed for the poly(silylenemethylenes) with repeating sequence [Si(CH₃)R-CH₂]_x, R=-O(CH₂)_NOC₆H₄C₆H₅. The model incorporates all first- and second-order interactions, as well as higher order interactions that are mandatory in some of the conformations. Chains with all possible stereochemical sequences prefer a local conformation that is a run of trans states at the C-Si bonds in the backbone. This preference arises from an attractive second-order interaction of the first methylene group in the side-chain bonded to chain atom i with the silicon atoms indexed i±2. Unperturbed chains have larger dimensions than the simpler chain in which R is merely a methyl group. The temperature coefficients of the unperturbed dimensions are large and negative. The preference of unperturbed atactic, isotactic, and syndiotactic chains for the same local conformation may contribute to the facile formation of smectic phases by the presumably atactic chain, as reported by Park et al. [Macromolecules 35 (2002) 2776].     

Constructing side chains on near-native main chains for ab initio protein structure prediction

Is there value in constructing side chains while searching proteinconformational space during an ab initio simulation? If so,what is the most computationally efficient method for constructingthese side chains? To answer these questions, four publishedapproaches were used to construct side chain conformations ona range of near-native main chains generated by ab initio proteinstructure prediction methods. The accuracy of these approacheswas compared with a naive approach that selects the most frequentlyobserved rotamer for a given amino acid to construct side chains.An all-atom conditional probability discriminatory functionis useful at selecting conformations with overall low all-atomroot mean square deviation (r.m.s.d.) and the discriminationimproves on sets that are closer to the native conformation.In addition, the naive approach performs as well as more sophisticatedmethods in terms of the percentage of     

Study of three-dimensional polystyrene networks containing linear chains: 2. Relaxation spectrum of linear chains

A study of the relaxation phenomenon in polystyrene networks containing linear polystyrene chains of high molecular weight has been carried out using measurements in methylcyclohexane and in the dry state by dynamic sinusoidal deformation and static stress relaxation. It is shown that the relaxation of the free chains contained in the network is (i) proportional to (1 ? v²₂) where v₂ is the volume fraction of the crosslinked network in the dry state, and (ii) depends very little on their concentration in the network. The distribution of relaxation time shows a peak related to the glass transition of the networks and a second peak corresponding to the spectrum of the linear chains of high molecular weight.     

Modification of polypeptide materials by Thiol-X chemistry

Thiol-X chemistry has proven to be a valuable toolbox for modification of peptides, proteins, monomers, and polymers. Recently, this has become especially true for the modification of polypeptides (monomers or polymers), which has resulted in a plethora of novel polymers and materials. With this in mind, this highlight focuses on the recent literature concerning the modification of polypeptides by the use of thiol-X chemistry, in particular to synthetic polypeptides either at the monomer or polymer stage modified by thiol-ene, -Michael addition, and -yne chemistries.     

含氟低聚乙氧基醚链的合成

通过选择性单醚化反应合成并表征了含氟低聚乙氧基富π电子醚链以强吸电子基团—F作为封堵基团,利用其与缺电子联吡啶大环化合物自组装形成准轮烷,从而为合成在分子水平上具有调控功能的分子振荡元件提供实验和理论依据。