Amyloid fibrils are implicated in over 20 neurodegenerative diseases. The mechanisms of fibril structuring and formation are not only of medical and biological importance but are also relevant for material science and nanotechnologies due to the unique structural and physical properties of amyloids. We previously found that hen egg white lysozyme, homologous to the disease-related human lysozyme, can form left-handed giant ribbons, closing into nanotubes. By using matrix-assisted laser desorption ionization mass spectrometry analysis, we here identify a key component of such structures: the ILQINS hexapeptide. By combining atomic force microscopy and circular dichorism, we find that this fragment, synthesized by solid-phase peptide synthesis, also forms fibrillar structures in water at pH 2. However, all fibrillar structures formed possess an unexpected right-handed twist, a rare chirality within the corpus of amyloid experimental observations. We confirm by small- and wide-angle X-ray scattering and molecular dynamics simulations that these fibrils are composed of conventional left-handed β-sheets, but that packing stresses between adjacent sheets create this twist of unusual handedness. We also show that the right-handed fibrils represent a metastable state toward β-sheet-based microcrystals formation.
To afford chiral polyisocyanides with thermoresponsiveness may open new gates to enhance their functionality and to broaden their applications. Herein, we report the synthesis of a series of novel polyisocyanides carrying oligoethylene glycols (OEGs) modified dipeptides as the pendent groups. These polyisocyanides not only show different chiroptical properties but also possess characteristic thermoresponsive behavior. The corresponding monomers carrying different OEG units in the periphery are water-soluble, thus allowing their polymerization feasible in aqueous medium with NiCl 2 as the catalyst. For comparison, polyisocyanides were also prepared in organic solvents, such as dichloromethane and tetrahydrofuran. The effects of solvent and polymerization temperature as well as chemical structures of the pendants on the chiroptical properties of the resulting polymers were examined. The characteristic thermoresponsive behavior of these chiral polymers was investigated by 1 H NMR spectroscopy and turbidity measurements using UV/vis spectroscopy. The thermally induced aggregation processes were also followed by dynamic light scattering. It was found that the phase transition temperatures of these polymers were significantly influenced not only by the overall hydrophilicity but also by their secondary structures.
Combination of stimuli responsiveness with p-conjugated polymers possesses probabilities not only to provide these polymers with unique interesting properties but also to promote new functions including various optoelectronic properties, catalysis, ionic sensing, and chiral recognition. In the former part of this review, recent developments of stimuli-responsive polyacetylenes are surveyed, which act as receptors towards external stimuli such as solvent, temperature, pH, chiral compounds, metal cations, various anions, electricity, light, etc., to transduce to other signals or energies, which leads to a wide range of intriguing properties to mimic biological processes or applications to smart or intelligent materials. In the latter part, we introduce dendronized poly(phenylacetylene)s (PPAs) exhibiting interesting thermoresponsive and chiroptical properties. Thermoresponsiveness of these dendronized conjugated polymers shows synchronous influence on their helical and hydrated conformations.
Chiral polymers with simple chemical structures and high helical conformation stabilities are important for their applications as chiral supports and asymmetrical catalysts. We report herein the synthesis of a series of aliphatic polyisocyanides carrying proline pendants of different chiralities, and an investigation of the effects of the chemical structures of these pendants on the chiroptical properties of the polymers. The configuration of the chiral center at the 4-position of the proline pendants was changed from S to R to check its effect on the handedness of the helical conformation. To examine the effects of steric hindrance on the stabilities of the helical conformation for these aliphatic representatives, proline pendants with various substituents at both the carboxyl and amine terminals were designed. To further examine the steric effects of the proline pendants, aromatic counterparts were also prepared. In the latter case, the effects of hydrogen bonds between pendant units on the enhancement and stabilities of the helical conformation were investigated by switching from the ester to an amide linkage. The Cotton effects and signal intensities of both aliphatic and aromatic polyisocyanides from circular dichroism spectroscopy were compared based on the bulkiness of the pendant groups, solvent polarities, and solution temperatures. It was found that highly stable helical conformations of polyisocyanides could be imposed by small bulky monoproline pendants.
Nucleic acid drugs can treat diseases caused by defective or abnormal genes. Herein, the mechanism of non‐viral vectors for nucleic acid drug delivery is described. This review introduce non‐viral vectors for nucleic acid drug delivery, including the nucleic acid‐carrier conjugate, proteins and peptides‐based nanoparticles, polysaccharides, and other biological macromolecules‐based nanoparticles consisting of lipid nanoparticles, synthetic polymers‐based nanoparticles, inorganic nanoparticles, and organic–inorganic hybrid nanoparticles. Finally, the challenges and prospects of non‐viral vectors for nucleic acid drug delivery are discussed.
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