Charge‐Induced Secondary Structure Transformation of Amyloid‐Derived Dipeptide Assemblies from β‐Sheet to α‐Helix

Secondary structures such as α‐helix and β‐sheet are the major structural motifs within the three‐dimensional geometry of proteins. Therefore, structure transitions from β‐sheet to α‐helix not only can serve as an effective strategy for the therapy of neurological diseases through the inhibition of β‐sheet aggregation but also extend the application of α‐helix fibrils in biomedicine. Herein, we present a charge‐induced secondary structure transition of amyloid‐derived dipeptide assemblies from β‐sheet to α‐helix. We unravel that the electrostatic (charge) repulsion between the C‐terminal charges of the dipeptide molecules are responsible for the conversion of the secondary structure. This finding provides a new perspective to understanding the secondary structure formation and transformation in the supramolecular organization and life activity.     

Effects of solvent,casting temperature,and guest/host stoichiometries on the properties of shape memory material based on partial α‐CD‐PEG inclusion complex

A series of supramolecular inclusion complex (IC) films were formed by threading α‐cyclodextrin (α‐CD) molecules over poly(ethylene glycol) (PEG), according to the designed ratio of α‐CD/PEG. Because of containing α‐CD‐PEG inclusion crystallites as physical crosslinks and uncovered PEG crystallites as “switch phase”, the resulting supramolecular α‐CD‐PEG partial ICs displayed a shape memory effect. The properties of the materials were investigated by ¹H‐NMR, X‐ray diffraction (XRD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and swelling measurement. It was found that the casting temperature, solvent, and the ratio of α‐CD‐PEG inclusion/PEG had great influence on the formation and properties of α‐CD‐PEG partial ICs. The modes of complexes on different conditions were proposed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 951–957, 2010     

Construction of different supramolecular polymer systems by combining the host–guest and hydrogen‐bonding interactions

Poly(ethylene glycol) (PEG) can form either the inclusion complex with α‐cyclodextrins (α‐CDs) through host–guest interactions or the interpolymer complex with poly(acrylic acid) (PAA) through hydrogen‐bonding interaction. Mixing α‐CD, PEG, and PAA ternary components in an aqueous solution, the competition between host–guest and hydrogen‐bonding interactions occurs. Increasing feed ratio of α‐CD:EG:AA from 0:1:1 to 0.2:1:1 (molar ratio), various interesting supramolecular polymer systems, such as hydrogen‐bonding complex, dynamic polyrotaxane, crystalline inclusion complex, and thermoresponsive hydrogel, are successively obtained. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 1114–1120, 2008     

Heat‐Induced Supramolecular Organogels Composed of α‐Cyclodextrin and “Jellyfish‐Like” β‐Cyclodextrin–Poly(ε‐caprolactone)

In general, the complexation and gelation behavior between biocompatible poly(ε‐caprolactone) (PCL) derivatives and α‐cyclodextrin (α‐CD) is extensively studied in water, but not in organic solvents. In this article, the complexation and gelation behavior between α‐CD and multi‐arm polymer β‐cyclodextrin‐PCL (β‐CD‐PCL) with a unique “jellyfish‐like” structure are thoroughly investigated in organic solvent N,N‐dimethylformamide and a new heat‐induced organogel is obtained. However, PCL linear polymers cannot form organogels under the same condition. The complexation is characterized by rheological measurements, DSC, XRD, and SEM. The SEM images reveal that the complexes between β‐CD‐PCL and α‐CD present a novel topological helix porous structure which is distinctly different from the lamellar structure formed by PCL linear polymers and α‐CD, suggesting the unique “jellyfish‐like” structure of β‐CD‐PCL is crucial for the formation of the organogels. This research may provide insight into constructing new supramolecular organogels and potential for designing new functional biomaterials. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013 , 51, 1598–1606     

Self‐assembly of star‐shaped polystyrene‐block‐polypeptide copolymers synthesized by the combination of atom transfer radical polymerization and ring‐opening living polymerization of α‐amino acid‐N‐carboxyanhydrides

The self‐assembling nature and phase‐transition behavior of a novel class of triarm, star‐shaped polymer–peptide block copolymers synthesized by the combination of atom transfer radical polymerization and living ring‐opening polymerization of α‐amino acid‐N‐carboxyanhydride are demonstrated. The two‐step synthesis strategy adopted here allows incorporating polypeptides into the usual synthetic polymers via an amido–amidate nickelacycle intermediate, which is used as the macroinitiator for the growth of poly(γ‐benzyl‐L ‐glutamate). The characterization data are reported from analyses using gel permeation chromatography and infrared, ¹H NMR, and ¹³C NMR spectroscopy. This synthetic scheme grants a facile way to prepare a wide range of polymer–peptide architectures with perfect microstructure control, preventing the formation of homopolypeptide contaminants. Studies regarding the supramolecular organization and phase‐transition behavior of this class of polymer‐block‐polypeptide copolymers have been accomplished with X‐ray diffraction, infrared spectroscopy, and thermal analyses. The conformational change of the peptide segment in the block copolymer has been investigated with variable‐temperature infrared spectroscopy. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2774–2783, 2006     

Thermal stability of the secondary structure of poly(alpha,L-glutamate) in self-assembled complexes as studied by molecular dynamics in chloroform solution

The thermal stability of the self-assembled complexes formed by alkyltrimethylammonium surfactants and poly(alpha,l-glutamate) is investigated in dilute chloroform solution by molecular dynamics simulations. By applying temperatures ranging from 300 to 500 K, we observed an extraordinary stability of the alpha-helix adopted by the polypeptide during a total of 48 ns. The multiple electrostatic interactions formed between the surfactant chains and the polyanion play a crucial role in this stability since they are responsible for the inaccessibility of the solvent molecules to the helix even at high temperatures.     

Solvent‐dependent formation of inclusion complexes between methylated cyclodextrins and biodegradable polymers

The inclusion complexes (ICs) of unmodified natural and methylated α‐cyclodextrins (CDs) with biodegradable polymers, polyethylene glycol and poly(ε‐caprolactone), were prepared by two methods, that is, the one using water and the other using chloroform as the solvent for the respective CDs. The ICs obtained were characterized by IR, WAXD, DSC, and ¹³C CP/MAS NMR. It was found that the possibility and the phenomena of IC formation could be varied with the degree of methyl substitution of CD as well as the type of solvents used. Methylated α‐CDs showed the prominent characteristics of IC formation with polymers in the case where chloroform was used than in the case where water was used as the solvent for CDs, while vice versa in the case of native α‐CD. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 879–891, 2008     

Self‐assembly of supramolecular polymers into tunable helical structures

There is growing interest in the design of synthetic molecules that are able to self‐assemble into a polymeric chain with compact helical conformations, which is analogous to the folded state of natural proteins. Herein, we highlight supramolecular approach to the formation of helical architectures and their conformational changes driven by external stimuli. Helical organization in synthetic self‐assembling systems can be achieved by the various types of noncovalent interactions, which include hydrogen bonding, solvophobic effects, and metal‐ligand interactions. Since the external environment can have a large influence on the strength and configuration of noncovalent interactions between the individual components, stimulus‐induced alterations in the intramolecular noncovalent interactions can result in dynamic conformational change of the supramolecular helical structure thus, driving significant changes in the properties of the materials. Therefore, these supramolecular helices hold great promise as stimuli‐responsive materials. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1925–1935, 2008     

Redox,ionic strength,and pH sensitive supramolecular polymer assemblies

Formation of micelle‐type assembly from supramolecular complexation of a surfactant and an oppositely charged homopolymer is demonstrated. The lower CAC observed for these assemblies suggest that the electrostatic interaction provides an amphiphilic homopolymer‐like structure. The stimulus‐induced disassembly of these supramolecular structures has been accomplished with variations in redox characteristics, ionic strength, and pH of the medium. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1052–1060, 2009     

New solvent for polyrotaxane. II. Dissolution behavior of polyrotaxane in ionic liquids and preparation of ionic liquid‐containing slide‐ring gels

The dissolution behavior of polyrotaxanes, consisting of α‐cyclodextrin and poly(ethylene glycol), with different molecular weights (2000 and 35,000) was investigated. Halogen‐containing ionic liquids, such as chlorides or bromides, were found to be good solvents for polyrotaxanes, regardless of their cations. Dissolution required a high temperature (above 90 °C), while intensive heating over 105 °C seemed to cause decomposition of the polyrotaxane. The discovery of new solvents for polyrotaxane was applied in the preparation of ionic liquid‐containing slide‐ring gels (SR gels), that is supramolecular networks of polyrotaxane swollen with ionic liquids, using a devised “non‐drying” technique accompanied by solvent exchange. Significant swelling of the SR gels with the ionic liquids was confirmed by dynamic mechanical measurements. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 1985–1994, 2006     

Para‐linked and meta‐linked cationic water‐soluble fluorene‐containing poly(aryleneethynylene)s: Conformational changes and their effects on iron–sulfur protein detection

Four para‐linked or meta‐linked cationic water‐soluble fluorene‐containing poly(aryleneethynylene)s (PAEs) were synthesized to investigate the solvent‐induced π‐stacked self‐assembly. These PAE backbones are composed of fluorenylene and phenylene units, which are alternatively linked by ethynylene bonds. UV–vis absorption and photoluminescence spectra were used to study their conformational changes as solvent was gradually changed from MeOH to H₂O. In pure water, with gradually increased meta‐phenylene content (0, 50, and 100%), they underwent a gradual transition process of conformation from disordered aggregate structure to helix structure, which was not compactly folded. Moreover, the polymer with an ammonium‐functionalized side chain on the meta‐phenylene unit appeared to adopt a more incompact or extended helix conformation than the corresponding one without this side chain. Furthermore, the conformational changes of these cationic PAEs in H₂O were used to study their effects on biological detection. Rubredoxin (Rd), a type of anionic iron–sulfur‐based electron transfer protein, was chosen to act as biological analyte in the fluorescence quenching experiments of these polymers. Preliminary results suggest that they all exhibit amplified fluorescence quenching, and that the polymer with more features of helix conformation tends to be quenched by Rd more efficiently. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5424–5437, 2006     

Supramolecular micellization and pH‐inducible gelation of a hydrophilic block copolymer by block‐specific threading of α‐cyclodextrin

A poly(ethylene glycol)‐b‐poly(L ‐lysine) diblock copolymer (PEG‐b‐PLL) was synthesized. Micellization of this hydrophilic copolymer due to the block‐specific threading of α‐cyclodextrin (α‐CD) molecules onto the polyethylene glycol (PEG) block yielded supramolecular‐structured nanoparticles, which undergoes pH‐inducible gelation in aqueous media. The pH‐inducible gelation of supramolecular micelle in water appeared to be completely reversible upon pH changes. The synergetic effect of selective complexation between PEG block and α‐CD and the pH‐inducible hydrophobic interaction between PLL blocks at pH 10 was believed to be the driving force for the formation of the supramolecular hydrogel. ¹H NMR and wide angle X‐ray diffraction (WAXD) were employed to confirm the inclusion complexation between α‐CD and PEG block. Meanwhile, the morphology of the micellized nanoparticles was investigated by transmission electron microscopy (TEM). The thermal stability of inclusion complexes (ICs) was investigated and the rheologic experiment was conducted to reveal the micelle‐gel transition. Such pH‐induced reversible micelle‐gel transition of the supramolecular aggregates may find applications in several fields, for example as advanced biomedical material possessing stimulus‐responsiveness. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 782–790, 2008     

Supramolecular inclusion complexes of star‐shaped poly(ε‐caprolactone) with α‐cyclodextrin

Both star‐shaped poly(ε‐caprolactone) (PCL) having 4 arms (4sPCL) and 6 arms (6sPCL) and linear PCL having 1 arm (LPCL) and 2 arms (2LPCL) were synthesized and then investigated for inclusion complexation with α‐cyclodextrin (α‐CD). The supramolecular inclusion complexes (ICs) were in detail characterized by ¹H NMR, differential scanning calorimetry, thermogravimetric analysis, wide angle X‐ray diffraction, solid‐state carbon nuclear magnetic resonance spectroscopy using cross‐polarization and magic‐angle spinning, and Fourier transform infrared, respectively. The stoichiometry (CL:CD, mol:mol) of all ICs increased with the increasing branch arm of PCL polymers, and it was in the order of α‐CD‐6sPCL1 ICs > α‐CD‐4sPCL ICs > α‐CD‐2LPCL ICs > α‐CD‐LPCL ICs. All analyses indicated that the branch arms of star‐shaped PCL polymers were included into the hydrophobic α‐CD cavities and their original crystalline properties were completely suppressed. Moreover, the ICs of star‐shaped PCL with α‐CD had a channel‐type crystalline structure similar to that formed between the linear PCL and α‐CD. Furthermore, the thermal stability of the free PCL polymers probably controlled that of the guest polymers included in the ICs. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4721–4730, 2005     

Spontaneous formation of narrowly‐distributed self‐assembly from polyamidoamine dendron‐poly(L‐lysine) block copolymers through helix‐coil transition of poly(L‐lysine) block

The self‐assembly of head‐tail type block copolymers composed of polyamidoamine dendron head block and poly(L ‐lysine) (PLL) tail block was studied using a light scattering technique and transmission electron microscopy. A PLL tail block in a head‐tail type block copolymer exhibits a coil‐to‐helix transition as a result of the change in solvent quality from water to methanol. When the PLL tail block takes a helical conformation in high methanol content, the resulting head‐tail type block copolymer has a defined three‐dimensional structure like that of a protein molecule. Self‐assemblies of such block copolymers having a totally fixed molecular shape spontaneously form polymersome‐like self‐assemblies with an extremely narrow size distribution through converging to a thermodynamically stable assembling state. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1217–1223, 2009     

Synthesis and properties of star‐shaped polymers by the ring‐opening polymerization of cyclic carbonate initiated with a trifunctional,poly(ethylene glycol)‐based surfactant

Amphiphilic, star‐shaped copolymers were synthesized by the ring‐opening polymerization of trimethylene carbonate initiated with a trifunctional, poly(ethylene glycol)‐based surfactant (polyoxyethylene sorbitan monolaurate) in the absence of any catalysts. The metal‐ and solvent‐free polymerization proceeded at 150 °C and afforded polyoxyethylene sorbitan monolaurate‐block‐poly(trimethylene carbonate) with number‐average molecular weights of 4500–11,900 in excellent yields. The copolymers successfully dispersed in a water/ethyl acetate (10/1 v/v) mixture, and the uniform suspension could contain a hydrophobic pigment and pyrene. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6633–6639, 2006     

Tunable morphologies of rhenium complex‐containing polystyrene‐block‐poly(2‐vinylpyridine) aggregates

Polystyrene‐block‐poly(2‐vinylpyridine) (PS‐b‐P2VP) diblock copolymer was functionalized with luminescent chlorotricarbonyl rhenium (I) phenanthroline complex in the presence of silver perchlorate. The copolymer‐metal complex showed high sensitivity to the solvent system. Different morphologies and dimensions of the rhenium complex within nanosized micelles were controlled by changing the solvent systems. Core‐embedded rhenium complex within micelles appear by adding methanol, a poor solvent for the copolymer‐metal complex, to the solution of common solvent tetrahydrofuran (THF); the number of the core‐embedded rhenium complex and the scale of the micelles are strongly related to the addition of methanol. Moreover, a novel morphology of corona‐embedded rhenium complex micelles was prepared by dropping the original THF solution of copolymer‐metal complex into water at a low pH value. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 2047–2053, 2008     

Simulation of the self‐assembly of poly(α‐glutamate) and dodecyltrimethylammonium: Diffusive role of the surfactant cations

The self‐assembly process of stoichiometric complexes formed by poly(α‐glutamate) and dodecyltrimethylammonium molecular cations has been studied at the atomistic by molecular dynamics simulations. The results presented in this work depict a time‐dependent succession of events. Among them, the formation of the assembled complex is an extraordinarily fast event. On the other side, the surfactant units do not influence the kinetics of the polypeptide folding process, showing that the characteristic independent organization experimentally detected for the charged groups and aliphatic tails has its reflection during the assembly process. Through these results, it is possible to infer new strategies to engineer the final nano‐organization that these stoichiometric complexes can adopt. The instantaneous assembly of the oppositely charged components allows a further kinetic control over the polypeptide folding process, which is expected to take place in time scales that are between 10 and 100 times larger than those explored in this work. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 917–924, 2008     

Synthesis and properties of biomimetic poly(L‐glutamate)‐b‐poly(2‐acryloyloxyethyllactoside)‐b‐poly(L‐glutamate) triblock copolymers

A novel class of biomimetic glycopolymer–polypeptide triblock copolymers [poly(L ‐glutamate)–poly(2‐acryloyloxyethyllactoside)–poly(L ‐glutamate)] was synthesized by the sequential atom transfer radical polymerization of a protected lactose‐based glycomonomer and the ring‐opening polymerization of β‐benzyl‐L ‐glutamate N‐carboxyanhydride. Gel permeation chromatography and nuclear magnetic resonance analyses demonstrated that triblock copolymers with defined architectures, controlled molecular weights, and low polydispersities were successfully obtained. Fourier transform infrared spectroscopy of the triblock copolymers revealed that the α‐helix/β‐sheet ratio increased with the poly(benzyl‐L ‐glutamate) block length. Furthermore, the water‐soluble triblock copolymers self‐assembled into lactose‐installed polymeric aggregates; this was investigated with the hydrophobic dye solubilization method and ultraviolet–visible analysis. Notably, this kind of aggregate may be useful as an artificial polyvalent ligand in the investigation of carbohydrate–protein recognition and for the design of site‐specific drug‐delivery systems. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5754–5765, 2004     

Inclusion complexes of α‐cyclodextrin and (AB)n block copolymers

Cyclodextrins thread onto polymer chains to form inclusion complexes, especially when the polymer is hydrophobic relative to the solvent. Selective threading might occur when the polymer architecture contains both hydrophobic and hydrophilic segments. α‐Cyclodextrin formed crystalline inclusion complexes with (AB)_n microblock copolymers, where the A block was a linear alkyl segment containing a single double bond and the B block was an exact length segment of poly(ethylene oxide). The complexes were isolated and characterized by solution and solid‐state NMR, X‐ray diffraction, differential scanning calorimetry, and thermogravimetric analysis. Each method confirmed complex formation and showed that the physical properties of the complexes were distinct from those of its individual components. The X‐ray data were consistent with known inclusion complexes having a channel or column crystal structure. The stoichiometry of the complex formation, 2.3 α‐cyclodextrin rings per polymer repeat unit, was determined by NMR analysis of the complexes and from an analysis of the inclusion complex yields. The data suggest that the inclusion complex stoichiometry is defined by the increasing insolubility of the polymer–cyclodextrin complex. Solid‐state NMR data were consistent with a preference for threading onto hydrophobic segments of the (AB)_n polymer. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 2731–2739, 2001     

Stability and Unfolding Mechanism of the N‐terminal β‐Hairpin from [2Fe‐2S] Ferredoxin I by Molecular Dynamics Simulations

The stability and unfolding mechanism of the N‐terminal β‐hairpin of the [2Fe‐2S] ferredoxin I from the blue‐green alga Aphanothece sacrum in pure methanol, 40% (v/v) methanol‐water, and pure water systems were investigated by 10 ns molecular dynamics simulations under periodic boundary conditions. The β‐hairpin was mostly in its native‐like state in pure methanol, whereas it unfolds dramatically following the ‘zip‐up’ mechanism when it was placed in pure water. Both interstrand and inside‐turn hydrogen bonds account for the stability of the β‐hairpin in its native‐like conformation, whereas hydrophobic interactions among nonpolar side chains are responsible for maintaining its stable loop‐like intermediate structures in 40% (v/v) methanol‐water. Reducing solvent polarity seems to increase the stability of the β‐hairpin in its native‐like structure. Methanol is likely to mimic the partially hydrophobic environment around the N‐terminal β‐hairpin by the subsequent α‐helix.