共查询到20条相似文献,搜索用时 15 毫秒
1.
《Macromolecular bioscience》2017,17(3)
Affinity‐based cell separation is label‐free and highly specific, but it is difficult to efficiently and gently release affinity‐captured cells due to the multivalent nature of cell‐material interactions. To address this challenge, we have developed a platform composed of a capture substrate and a cell‐releasing molecular trigger. The capture substrate is functionalized with a cell‐capture antibody and a coiled‐coil A . The cell‐releasing molecular trigger B ‐PEG (polyethylene glycol), a conjugate of a coiled‐coil B and polyethylene glycol, can drive efficient and gentle release of the captured cells, because A / B heterodimerization brings B ‐PEG to the substrate and PEG chains adopt extended conformations and break nearby multivalent antibody‐biomarker interactions. No enzymes or excessive shear stress are involved, and the released cells have neither external molecules attached nor endogenous cell‐surface molecules cleaved, which is critical for the viability, phenotype, and function of sensitive cells.
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Concluding the Amyloid Formation Pathway of a Coiled‐Coil‐Based Peptide from the Size of the Critical Nucleus 下载免费PDF全文
Dr. Ulla I. M. Gerling Dr. Markus S. Miettinen Prof. Dr. Beate Koksch 《Chemphyschem》2015,16(1):108-114
The size of the critical nucleus acting as intermediate in the amyloid formation of a model peptide is calculated. The theoretical approach is based on experimentally determined amyloid formation rates and gives new insights into the amyloid formation pathway. 相似文献
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Valeria Castelletto Dr. Ian W. Hamley Prof. Rohan A. Hule Dr. Darrin Pochan Prof. 《Angewandte Chemie (International ed. in English)》2009,48(13):2317-2320
An addition to the family : The introduction of β‐amino acid residues into a modified amyloid β peptide fragment resulted in well‐defined helical nanoribbons (see cryo‐TEM image) comprising β strands mainly oriented perpendicular to the ribbon axis. The nanoribbons order into a flow‐aligning nematic phase at higher concentration. The β‐strand nanoribbon structure is an addition to the known set of secondary structures adopted by β‐peptides.
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Yang Zhou Xin‐Ping Long Qing‐Xuan Zeng Chao‐Yang Zhang 《Macromolecular rapid communications》2013,34(10):883-886
A Dissipative particle dynamics (DPD) simulations are performed to study the cooperative self‐assembly of coil–rod–coil triblock copolymers and nanoparticles in solution. The results show that, when the nanoparticle concentration exceeds a given value, the ternary systems can form a novel nanocage composed of two‐end coil‐caps and middle rod‐linkers. The novel nanocage is very similar to the real bird cage and the captured nanoparticles like the bird. It is the first nanocage from the self‐assembly of coil–rod–coil triblock copolymers. This may be used for the release of drugs and fertilizers, or as nanoreactors.
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Characterizing Methyl‐Bearing Side Chain Contacts and Dynamics Mediating Amyloid β Protofibril Interactions Using 13Cmethyl‐DEST and Lifetime Line Broadening 下载免费PDF全文
Dr. Nicolas L. Fawzi Dr. David S. Libich Dr. Jinfa Ying Dr. Vitali Tugarinov Dr. G. Marius Clore 《Angewandte Chemie (International ed. in English)》2014,53(39):10345-10349
Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced 15N dark‐state exchange saturation transfer (DEST) and 15N lifetime line‐broadening to study solution backbone dynamics and position‐specific binding probabilities for amyloid β (Aβ) monomers in exchange with large (2–80 MDa) protofibrillar Aβ aggregates. Here we use 13Cmethyl DEST and lifetime line‐broadening to probe the interactions and dynamics of methyl‐bearing side chains in the Aβ‐protofibril‐bound state. We show that all methyl groups of Aβ40 populate direct‐contact bound states with a very fast effective transverse relaxation rate, indicative of side‐chain‐mediated direct binding to the protofibril surface. The data are consistent with position‐specific enhancements of 13Cmethyl‐${R{{{\rm tethered}\hfill \atop 2\hfill}}}$ values in tethered states, providing further insights into the structural ensemble of the protofibril‐bound state. 相似文献
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A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly 下载免费PDF全文
Dr. Erika Andreetto Dipl.‐Chem. Eleni Malideli Dr. Li‐Mei Yan Dipl.‐Ing. Michael Kracklauer MSc. Karine Farbiarz Dipl.‐Chem. Marianna Tatarek‐Nossol Prof. Dr. Gerhard Rammes M. Sc. Elke Prade Tatjana Neumüller Dr. Andrea Caporale M. Sc. Anna Spanopoulou B. Sc. Maria Bakou Prof. Dr. Bernd Reif Prof. Dr. Aphrodite Kapurniotu 《Angewandte Chemie (International ed. in English)》2015,54(44):13095-13100
The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well. 相似文献
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Ming‐Shan Tsai U. Narasimha Rao Jeng‐Rong Wang Chung‐Hao Liang Ming‐Chang P. Yeh 《中国化学会会志》2001,48(5):869-876
Semihydrogenation of α,β‐unsaturated ynoates and ‐ynones bearing a γ‐alkoxy group can be performed using triphenylphosphine and water. α,β‐Unsaturated ynoates were reduced to a mixture of cis and trans α,β‐unsaturated enoates, whereas, ynones were reduced to trans α,β‐unsaturated enones as the only products. 相似文献
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Qing Li Zackary N. Scholl Prof. Piotr E. Marszalek 《Angewandte Chemie (International ed. in English)》2014,53(49):13429-13433
The folding behaviors and mechanisms of large multidomain proteins have remained largely uncharacterized, primarily because of the lack of appropriate research methods. To address these limitations, novel mechanical folding probes have been developed that are based on antiparallel coiled‐coil polypeptides. Such probes can be conveniently inserted at the DNA level, at different positions within the protein of interest where they minimally disturb the host protein structure. During single‐molecule force spectroscopy measurements, the forced unfolding of the probe captures the progress of the unfolding front through the host protein structure. This novel approach allows unfolding pathways of large proteins to be directly identified. As an example, this probe was used in a large multidomain protein with ten identical ankyrin repeats, and the unfolding pathway, its direction, and the order of sequential unfolding were unequivocally and precisely determined. This development facilitates the examination of the folding pathways of large proteins, which are predominant in the proteasomes of all organisms, but have thus far eluded study because of the technical limitations encountered when using traditional techniques. 相似文献
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Masato Ikeda Dr. Shuichi Haraguchi Munenori Numata Dr. Seiji Shinkai Prof. 《化学:亚洲杂志》2007,2(10):1290-1298
We synthesized a semiartificial β‐1,3‐glucan, curdlan with dialkylaniline groups (CUR‐DA), that bears chromophoric aromatic groups at its peripheral positions. Spectroscopic studies as well as microscopic observations indicate that CUR‐DA adopts a triple‐stranded helical structure in water‐ or methanol‐rich solutions of dimethyl sulfoxide (DMSO). This triple‐stranded helical structure exhibits high thermal stability and resistance to base, attributes that are similar to those of the triple‐stranded helical structure of native β‐1,3‐glucans such as schizophyllan. Moreover, we found that the stability of the triple‐stranded helical structure can be easily modulated by solvent composition and metal‐ion (Zn2+) binding. As β‐1,3‐glucan polysaccharides are known to serve as “polymeric” hosts, including certain DNA molecules, carbon nanotubes, and conjugated polymers, and complexation occurs only with the single‐stranded structure, this information is very useful for the creation of these attractive polymeric composites, the controlled release of DNA, and so on. 相似文献
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Exploiting Aromatic Interactions for β‐Peptide Foldamer Helix Stabilization: A Significant Design Element 下载免费PDF全文
Dr. István M. Mándity Dr. Antonella Monsignori Dr. Lívia Fülöp Prof. Dr. Enikö Forró Prof. Dr. Ferenc Fülöp 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(16):4591-4597
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
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β‐Bromo‐α,β‐unsaturated ketones are condensed with arylhydrazines to form hydrazones, which are in situ intramolecularly cyclized into 3‐substituted 1‐aryl‐1 H‐pyrazoles under a catalytic system of Pd(OAc)2/1,3‐bis(diphenylhosphino)propane (dppp)/NaOtBu. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
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NH2SO3H–SiO2/water as a novel catalytic system was used for the synthesis of (α,β‐unsaturated) β‐amino ketones via aza‐Michael reaction at reflux conditions. The methodology was of general applicability and the catalyst exhibited activity up to five cycles. The catalyst was characterized for the first time using FT‐IR, X‐ray diffraction and scanning electron microscopic–energy dispersion analytical X‐ray. The stability of the catalyst was evaluated by differential scanning calorimetry and TGA/differential thermal analysis. High efficiency of the catalyst along with its recycling ability and the rather low loading demonstrated in reactions are the merits of the presented protocol. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
16.
Qing He Dr. Yu‐Fei Ao Prof. Zhi‐Tang Huang Prof. De‐Xian Wang 《Angewandte Chemie (International ed. in English)》2015,54(40):11785-11790
Anion–π interactions have been widely studied as new noncovalent driving forces in supramolecular chemistry. However, self‐assembly induced by anion–π interactions is still largely unexplored. Herein we report the formation of supramolecular amphiphiles through anion–π interactions, and the subsequent formation of self‐assembled vesicles in water. With the π receptor 1 as the host and anionic amphiphiles, such as sodium dodecylsulfate (SDS), sodium laurate (SLA), and sodium methyl dodecylphosphonate (SDP), as guests, the sequential formation of host–guest supramolecular amphiphiles and self‐assembled vesicles was demonstrated by SEM, TEM, DLS, and XRD techniques. The intrinsic anion–π interactions between 1 and the anionic amphiphiles were confirmed by crystal diffraction, HRMS analysis, and DFT calculations. Furthermore, the controlled disassembly of the vesicles was promoted by competing anions, such as NO3?, Cl?, and Br?, or by changing the pH value of the medium. 相似文献
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A Self‐Assembled Spherical Complex Displaying a Gangliosidic Glycan Cluster Capable of Interacting with Amyloidogenic Proteins 下载免费PDF全文
Dr. Sota Sato Yutaka Yoshimasa Dr. Daishi Fujita Dr. Maho Yagi‐Utsumi Dr. Takumi Yamaguchi Prof. Dr. Koichi Kato Prof. Dr. Makoto Fujita 《Angewandte Chemie (International ed. in English)》2015,54(29):8435-8439
Physiological and pathological functions of glycans are promoted through their clustering effects as exemplified by a series of gangliosides, sialylated glycosphingolipids, which serve as acceptors for bacterial toxins and viruses. Furthermore, ganglioside GM1 clusters on neuronal cell membranes specifically interact with amyloidogenic proteins, triggering their conformational transitions and leading to neurodegeneration. Here we develop a self‐assembled spherical complex that displays a cluster of the GM1 pentasaccharide, and successfully demonstrate its ability to interact with amyloid β and α‐synuclein. Due to the lack of hydrophobic lipid moieties, which would stably trap these cohesive proteins or give rise to toxic aggregates, this artificial cluster enabled NMR spectroscopic characterization of the early encounter stage of protein interactions with its outer carbohydrate moieties, which were not observable with previous glycan clusters. 相似文献
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Xue Liu Yang Liu Zhenkun Zhang Fan Huang Qian Tao Rujiang Ma Yingli An Prof. Linqi Shi 《Chemistry (Weinheim an der Bergstrasse, Germany)》2013,19(23):7437-7442
We have fabricated a mixed‐shell polymeric micelle (MSPM) that closely mimics the natural molecular chaperone GroEL? GroES complex in terms of structure and functionality. This MSPM, which possesses a shared PLA core and a homogeneously mixed PEG and PNIAPM shell, is constructed through the co‐assembly of block copolymers poly(lactide‐b‐poly(ethylene oxide) (PLA‐b‐PEG) and poly(lactide)‐b‐poly(N‐isopropylacryamide) (PLA‐b‐PNIPAM). Above the lower critical solution temperature (LCST) of PNIPAM, the MSPM evolves into a core–shell–corona micelle (CSCM), as a functional state with hydrophobic PNIPAM domains on its surface. Light scattering (LS), TEM, and fluorescence and circular dichroism (CD) spectroscopy were performed to investigate the working mechanism of the chaperone‐like behavior of this system. Unfolded protein intermediates are captured by the hydrophobic PNIPAM domains of the CSCM, which prevent harmful protein aggregation. During cooling, PNIPAM reverts into its hydrophilic state, thereby inducing the release of the bound unfolded proteins. The refolding process of the released proteins is spontaneously accomplished by the presence of PEG in the mixed shell. Carbonic anhydrase B (CAB) was chosen as a model to investigate the refolding efficiency of the released proteins. In the presence of MSPM, almost 93 % CAB activity was recovered during cooling after complete denaturation at 70 °C. Further results reveal that this MSPM also works with a wide spectrum of proteins with more‐complicated structures, including some multimeric proteins. Given the convenience and generality in preventing the thermal aggregation of proteins, this MSPM‐based chaperone might be useful for preventing the toxic aggregation of misfolded proteins in some diseases. 相似文献
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Christian Chapuis Michel Barthe Carole Cantatore Christine Saint‐Lger Patrick Wyss 《Helvetica chimica acta》2006,89(11):2638-2653
To complete our panorama in structure–activity relationships (SARs) of sandalwood‐like alcohols derived from analogues of α‐campholenal (= (1R)‐2,2,3‐trimethylcyclopent‐3‐ene‐1‐acetaldehyde), we isomerized the epoxy‐isopropyl‐apopinene (?)‐ 2d to the corresponding unreported α‐campholenal analogue (+)‐ 4d (Scheme 1). Derived from the known 3‐demethyl‐α‐campholenal (+)‐ 4a , we prepared the saturated analogue (+)‐ 5a by hydrogenation, while the heterocyclic aldehyde (+)‐ 5b was obtained via a Bayer‐Villiger reaction from the known methyl ketone (+)‐ 6 . Oxidative hydroboration of the known α‐campholenal acetal (?)‐ 8b allowed, after subsequent oxidation of alcohol (+)‐ 9b to ketone (+)‐ 10 , and appropriate alkyl Grignard reaction, access to the 3,4‐disubstituted analogues (+)‐ 4f,g following dehydration and deprotection. (Scheme 2). Epoxidation of either (+)‐ 4b or its methyl ketone (+)‐ 4h , afforded stereoselectively the trans‐epoxy derivatives 11a,b , while the minor cis‐stereoisomer (+)‐ 12a was isolated by chromatography (trans/cis of the epoxy moiety relative to the C2 or C3 side chain). Alternatively, the corresponding trans‐epoxy alcohol or acetate 13a,b was obtained either by reduction/esterification from trans‐epoxy aldehyde (+)‐ 11a or by stereoselective epoxidation of the α‐campholenol (+)‐ 15a or of its acetate (?)‐ 15b , respectively. Their cis‐analogues were prepared starting from (+)‐ 12a . Either (+)‐ 4h or (?)‐ 11b , was submitted to a Bayer‐Villiger oxidation to afford acetate (?)‐ 16a . Since isomerizations of (?)‐ 16 lead preferentially to β‐campholene isomers, we followed a known procedure for the isomerization of (?)‐epoxyverbenone (?)‐ 2e to the norcampholenal analogue (+)‐ 19a . Reduction and subsequent protection afforded the silyl ether (?)‐ 19c , which was stereoselectively hydroborated under oxidative condition to afford the secondary alcohol (+)‐ 20c . Further oxidation and epimerization furnished the trans‐ketone (?)‐ 17a , a known intermediate of either (+)‐β‐necrodol (= (+)‐(1S,3S)‐2,2,3‐trimethyl‐4‐methylenecyclopentanemethanol; 17c ) or (+)‐(Z)‐lancifolol (= (1S,3R,4Z)‐2,2,3‐trimethyl‐4‐(4‐methylpent‐3‐enylidene)cyclopentanemethanol). Finally, hydrogenation of (+)‐ 4b gave the saturated cis‐aldehyde (+)‐ 21 , readily reduced to its corresponding alcohol (+)‐ 22a . Similarly, hydrogenation of β‐campholenol (= 2,3,3‐trimethylcyclopent‐1‐ene‐1‐ethanol) gave access via the cis‐alcohol rac‐ 23a , to the cis‐aldehyde rac‐ 24 . 相似文献
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Summary: This article reports the application of surface plasmon resonance (SPR) to monitor the interaction between polymer‐DNA complexes and glycoaminoglycans (GAG). The GAG selected was hyaluronic acid (HA). First a HA derivative containing a disulfide linkage was synthesized, enabling chemisorption onto a gold surface. Next, the interaction between different complexes (prepared using PEI or PDMAEMA) and HA was studied using SPR. This study clearly indicates that GAG‐polyplex interactions depend on the type of polymer selected and on the charge ratio of the polyplexes prepared.