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https://www.readbyqxmd.com/read/28449250/self-assembly-of-peptide-boroxoles-on-cis-dihydroxylated-oligoamide-templates-in-water
#1
André Wuttke, Armin Geyer
We develop templates that can be used to stabilize consistent oligomers of a bioactive peptide. In the present study, we synthesize oligomers of an antibody epitope from the amyloidogenic prion protein. Dynamic covalent chemistry is the basis for the spontaneous condensation of 2, 3, 4 or 6 peptides with qualified polyol templates presenting the required number of bioorthogonal ligation sites. To study this process in aqueous solution, the N-terminal amino acid of a 13-mer peptide is first acylated with 4-carboxy-benzoboroxole (1-hydroxy-1,3-dihydrobenzo[c][1,2] oxaborole-5-carboxylic acid) and then mixed with the template to obtain self-assembled miniamyloids of specified degree of oligomerization...
April 27, 2017: Journal of Peptide Science: An Official Publication of the European Peptide Society
https://www.readbyqxmd.com/read/28448032/a-tailored-hplc-purification-protocol-that-yields-high-purity-amyloid-beta-42-and-amyloid-beta-40-peptides-capable-of-oligomer-formation
#2
Christopher J A Warner, Subrata Dutta, Alejandro R Foley, Jevgenij A Raskatov
Amyloidogenic peptides such as the Alzheimer's disease-implicated Amyloid beta (Aβ), can present a significant challenge when trying to obtain high purity material. Here we present a tailored HPLC purification protocol to produce high-purity amyloid beta 42 (Aβ42) and amyloid beta 40 (Aβ40) peptides. We have found that the combination of commercially available hydrophobic poly(styrene/divinylbenzene) stationary phase, polymer laboratory reverse phase - styrenedivinylbenzene (PLRP-S) under high pH conditions, enables the attainment of high purity (>95%) Aβ42 in a single chromatographic run...
March 27, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28447666/in-situ-polymerisation-of-isoeugenol-as-a-green-consolidation-method-for-waterlogged-archaeological-wood
#3
Emily McHale, Calin C Steindal, Hartmut Kutzke, Tore Benneche, Stephen E Harding
Waterlogged archaeological wood is often in need of consolidation prior to drying to prevent shrinkage and cracking of the object. There is a need for new greener materials (than for example polyethylene glycol) and methods for consolidation to be developed. The use of wood-based components could provide good interaction between the consolidant and the remaining wood structure and would also support a shift away from fossil fuel-based materials to those with more sustainable sources. Based on this, lignin-like structures have been investigated for their ability to consolidate waterlogged archaeological wood...
April 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28447091/one-pot-synthesis-and-properties-of-well-defined-butadiynylene-bodipy-oligomers
#4
Wenxing Zhang, Wanle Sheng, Changjiang Yu, Yun Wei, Hua Wang, Erhong Hao, Lijuan Jiao
A homogeneous series of well-defined butadiynylene-BODIPY oligomers containing up to four BODIPY moieties have been synthesized from a "one-pot" oxidative homocoupling reaction of 2,6-di((trimethylsilyl)ethynyl)BODIPY. Further derivation of the resultant BODIPY dimer generates a water-soluble, red-emitting butadiyne-linked BODIPY dimer with pyridinium ions, which can ratiometrically detect viscosity, based on the two fluorescent conformers with the two BODIPY cores twisted and planar to each other depending on the viscosity of the environment...
April 27, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28446518/glutaminyl-cyclase-inhibitor-pq912-improves-cognition-in-mouse-models-of-alzheimer-s-disease-studies-on-relation-to-effective-target-occupancy
#5
Torsten Hoffmann, Antje Meyer, Ulrich Heiser, Stephan Kurat, Livia Bohme, Martin Kleinschmidt, Karl-Ulrich Buhring, Birgit Hutter-Paier, Martina Farcher, Hans-Ulrich Demuth, Inge Lues, Stephan Schilling
Numerous studies suggest that the majority of Aβ peptides deposited in Alzheimer's Disease (AD) is truncated and post-translationally modified at the N-terminus. Among these modified species, pyroglutamyl-Aβ (pE-Aβ including N3pE-Aβ42) has been identified as particularly neurotoxic. The N-terminal modification renders the peptide hydrophobic, accelerates formation of oligomers and reduces degradation by peptidases leading ultimately to the accumulation of the peptide and progression of AD. It has been shown, that the formation of pyroglutamyl residues is catalysed by glutaminyl cyclase (QC)...
April 26, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28445751/curcumin-dictates-divergent-fates-for-the-central-salt-bridges-in-amyloid-%C3%AE-40-and-amyloid-%C3%AE-42
#6
Bappaditya Chandra, Venus Singh Mithu, Debanjan Bhowmik, Anand Kant Das, Bankanidhi Sahoo, Sudipta Maiti, Perunthiruthy K Madhu
There are three specific regions in the Amyloid beta (Aβ) peptide sequence where variations cause enhanced toxicity in Alzheimer's disease: the N-terminus, the central salt bridge, and the C-terminus. Here, we investigate if there is a close conformational connection between these three regions, which may suggest a concerted mechanism of toxicity. We measure the effects of Zn(2+) and curcumin on Aβ40, and compare these with their previously reported effects on Aβ42. Aβ42 and Aβ40 differ only near the C-terminus, where curcumin interacts, while Zn(2+) interacts near the N-terminus...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28443913/the-effect-of-surface-roughness-and-viscoelasticity-on-rubber-adhesion
#7
A Tiwari, L Dorogin, A I Bennett, K D Schulze, W G Sawyer, M Tahir, G Heinrich, B N J Persson
Adhesion between silica glass or acrylic balls and silicone elastomers and various industrial rubbers is investigated. The work of adhesion during pull-off is found to strongly vary depending on the system, which we attribute to the two opposite effects: (1) viscoelastic energy dissipation close to an opening crack tip and (2) surface roughness. Introducing surface roughness on the glass ball is found to increase the work of adhesion for soft elastomers, while for the stiffer elastomers it results in a strong reduction in the work of adhesion...
April 26, 2017: Soft Matter
https://www.readbyqxmd.com/read/28443905/predicting-oligomer-polymer-compatibility-and-the-impact-on-nanoscale-segregation-in-thin-films
#8
Elise F D Sabattié, Jos Tasche, Mark R Wilson, Maximilian W A Skoda, Arwel Hughes, Torsten Lindner, Richard L Thompson
Compatibility between oligomers and polymers was systematically assessed using differential scanning calorimetry (DSC) and was correlated with similarity in saturation and solubility parameter. These measurements enabled validation of detailed volume of mixing calculations using Statistical Association Fluid Theory (SAFT-γ Mie) and molecular dynamics (MD) simulations, which can be used to predict behaviour beyond the experimentally accessible conditions. These simulations confirmed that squalane is somewhat more compatible with poly(isoprene), "PI" than poly(butadiene), "PB", and further enabled prediction of the temperature dependence of compatibility...
April 26, 2017: Soft Matter
https://www.readbyqxmd.com/read/28442388/microbial-secretion-of-lactate-enriched-oligomers-for-efficient-conversion-into-lactide-a-biological-shortcut-to-polylactide
#9
Camila Utsunomia, Ken'ichiro Matsumoto, Sakiko Date, Chiaki Hori, Seiichi Taguchi
Recently, we have succeeded in establishing the microbial platform for the secretion of lactate (LA)-based oligomers (D-LAOs), which consist of D-LA and d-3-hydroxybutyrate (d-3HB). The secretory production of D-LAOs was substantially enhanced by the supplementation of diethylene glycol (DEG), which resulted in the generation of DEG-capped oligomers at the carboxyl terminal (referred as D-LAOs-DEG). The microbial D-LAOs should be key compounds for the synthesis of lactide, an important intermediate for polylactides (PLAs) production, eliminating the costly chemo-oligomerization step in the PLA production process...
April 22, 2017: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28441058/protein-misfolding-diseases
#10
F Ulrich Hartl
The majority of protein molecules must fold into defined three-dimensional structures to acquire functional activity. However, protein chains can adopt a multitude of conformational states, and their biologically active conformation is often only marginally stable. Metastable proteins tend to populate misfolded species that are prone to forming toxic aggregates, including soluble oligomers and fibrillar amyloid deposits, which are linked with neurodegeneration in Alzheimer and Parkinson disease, and many other pathologies...
April 24, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28440371/role-of-uncrosslinked-chains-in-droplets-dynamics-on-silicone-elastomers
#11
Aurélie Hourlier-Fargette, Arnaud Antkowiak, Antoine Chateauminois, Sébastien Neukirch
We report an unexpected behavior in wetting dynamics on soft silicone substrates: the dynamics of aqueous droplets deposited on vertical plates of such elastomers exhibits two successive speed regimes. This macroscopic observation is found to be closely related to microscopic phenomena occurring at the scale of the polymer network: we show that uncrosslinked chains found in most widely used commercial silicone elastomers are responsible for this surprising behavior. A direct visualization of the uncrosslinked oligomers collected by water droplets is performed, evidencing that a capillarity-induced phase separation occurs: uncrosslinked oligomers are extracted from the silicone elastomer network by the water-glycerol mixture droplet...
April 25, 2017: Soft Matter
https://www.readbyqxmd.com/read/28439563/mechanism-of-vps4-hexamer-function-revealed-by-cryo-em
#12
Min Su, Emily Z Guo, Xinqiang Ding, Yan Li, Jeffrey T Tarrasch, Charles L Brooks, Zhaohui Xu, Georgios Skiniotis
Vps4 is a member of AAA(+) ATPase (adenosine triphosphatase associated with diverse cellular activities) that operates as an oligomer to disassemble ESCRT-III (endosomal sorting complex required for transport III) filaments, thereby catalyzing the final step in multiple ESCRT-dependent membrane remodeling events. We used electron cryo-microscopy to visualize oligomers of a hydrolysis-deficient Vps4 (vacuolar protein sorting-associated protein 4) mutant in the presence of adenosine 5'-triphosphate (ATP). We show that Vps4 subunits assemble into an asymmetric hexameric ring following an approximate helical path that sequentially stacks substrate-binding loops along the central pore...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28439266/a-novel-regulator-of-activation-induced-cytidine-deaminase-apobecs-in-immunity-and-cancer-schr%C3%A3-dinger-s-catalytic-pocket
#13
REVIEW
Justin J King, Mani Larijani
Activation-induced cytidine deaminase (AID) and its relative APOBEC3 cytidine deaminases boost immune response by mutating immune or viral genes. Because of their genome-mutating activities, AID/APOBECs are also drivers of tumorigenesis. Due to highly charged surfaces, extensive non-specific protein-protein/nucleic acid interactions, formation of polydisperse oligomers, and general insolubility, structure elucidation of these proteins by X-ray crystallography and NMR has been challenging. Hence, almost all available AID/APOBEC structures are of mutated and/or truncated versions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28438658/antioxidants-reduce-neurodegeneration-and-accumulation-of-pathologic-tau-proteins-in-the-auditory-system-after-blast-exposure
#14
Xiaoping Du, Matthew B West, Qunfeng Cai, Weihua Cheng, Donald L Ewert, Wei Li, Robert A Floyd, Richard D Kopke
Cochlear neurodegeneration commonly accompanies hair cell loss resulting from aging, ototoxicity, or exposures to intense noise or blast overpressures. However, the precise pathophysiological mechanisms that drive this degenerative response have not been fully elucidated. Our laboratory previously demonstrated that non-transgenic rats exposed to blast overpressures exhibited marked somatic accumulation of neurotoxic variants of the microtubule-associated protein, Tau, in the hippocampus. In the present study, we extended these analyses to examine neurodegeneration and pathologic Tau accumulation in the auditory system in response to blast exposure and evaluated the potential therapeutic efficacy of antioxidants on short-circuiting this pathological process...
April 21, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28437437/use-of-short-interfering-rna-delivered-by-cationic-liposomes-to-enable-efficient-down-regulation-of-ptpn22-gene-in-human-t-lymphocytes
#15
Valentina Perri, Marsha Pellegrino, Francesca Ceccacci, Anita Scipioni, Stefania Petrini, Elena Gianchecchi, Anna Lo Russo, Serena De Santis, Giovanna Mancini, Alessandra Fierabracci
Type 1 diabetes and thyroid disease are T cell-dependent autoimmune endocrinopathies. The standard substitutive administration of the deficient hormones does not halt the autoimmune process; therefore, development of immunotherapies aiming to preserve the residual hormonal cells, is of crucial importance. PTPN22 C1858T mutation encoding for the R620W lymphoid tyrosine phosphatase variant, plays a potential pathophysiological role in autoimmunity. The PTPN22 encoded protein Lyp is a negative regulator of T cell antigen receptor signaling; R620W variant, leading to a gain of function with paradoxical reduced T cell activation, may represent a valid therapeutic target...
2017: PloS One
https://www.readbyqxmd.com/read/28435985/elucidating-the-a%C3%AE-42-anti-aggregation-mechanism-of-action-of-tramiprosate-in-alzheimer-s-disease-integrating-molecular-analytical-methods-pharmacokinetic-and-clinical-data
#16
Petr Kocis, Martin Tolar, Jeremy Yu, William Sinko, Soumya Ray, Kaj Blennow, Howard Fillit, John A Hey
BACKGROUND: Amyloid beta (Aβ) oligomers play a critical role in the pathogenesis of Alzheimer's disease (AD) and represent a promising target for drug development. Tramiprosate is a small-molecule Aβ anti-aggregation agent that was evaluated in phase III clinical trials for AD but did not meet the primary efficacy endpoints; however, a pre-specified subgroup analysis revealed robust, sustained, and clinically meaningful cognitive and functional effects in patients with AD homozygous for the ε4 allele of apolipoprotein E4 (APOE4/4 homozygotes), who carry an increased risk for the disease...
April 24, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28434970/transfer-of-c-terminal-residues-of-human-apolipoprotein-a-i-to-insect-apolipophorin-iii-creates-a-two-domain-chimeric-protein-with-enhanced-lipid-binding-activity
#17
James V C Horn, Rachel A Ellena, Jesse J Tran, Wendy H J Beck, Vasanthy Narayanaswami, Paul M M Weers
Apolipophorin III (apoLp-III) is an insect apolipoprotein (18kDa) that comprises a single five-helix bundle domain. In contrast, human apolipoprotein A-I (apoA-I) is a 28kDa two-domain protein: an α-helical N-terminal domain (residues 1-189) and a less structured C-terminal domain (residues 190-243). To better understand the apolipoprotein domain organization, a novel chimeric protein was engineered by attaching residues 179 to 243 of apoA-I to the C-terminal end of apoLp-III. The apoLp-III/apoA-I chimera was successfully expressed and purified in E...
April 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28429726/verteporfin-induced-formation-of-protein-cross-linked-oligomers-and-high-molecular-weight-complexes-is-mediated-by-light-and-leads-to-cell-toxicity
#18
Eleni K Konstantinou, Shoji Notomi, Cassandra Kosmidou, Katarzyna Brodowska, Ahmad Al-Moujahed, Fotini Nicolaou, Pavlina Tsoka, Evangelos Gragoudas, Joan W Miller, Lucy H Young, Demetrios G Vavvas
Verteporfin (VP) was first used in Photodynamic therapy, where a non-thermal laser light (689 nm) in the presence of oxygen activates the drug to produce highly reactive oxygen radicals, resulting in local cell and tissue damage. However, it has also been shown that Verteporfin can have non-photoactivated effects such as interference with the YAP-TEAD complex of the HIPPO pathway, resulting in growth inhibition of several neoplasias. More recently, it was proposed that, another non-light mediated effect of VP is the formation of cross-linked oligomers and high molecular weight protein complexes (HMWC) that are hypothesized to interfere with autophagy and cell growth...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28429634/migration-of-oligomers-from-pet-determination-of-diffusion-coefficients-and-comparison-of-experimental-versus-modelled-migration
#19
Maria Hoppe, Roberta Fornari, Pim de Voogt, Roland Franz
Polyethylene terephthalate is increasingly used as food contact material for example in containers for beverage such as bottles for soft drinks, mineral water, juices and beer. Mass transport of substances present in packaging materials into the packed food and beverages is monitored to verify the food law compliance of the materials. PET is known to contain or give rise to migrants that are oligomers derived from the polymeric material. Until now their actual migration potential has been investigated only poorly...
April 21, 2017: Food Additives & Contaminants. Part A, Chemistry, Analysis, Control, Exposure & Risk Assessment
https://www.readbyqxmd.com/read/28429536/%C3%AE-mangostin-decreases-%C3%AE-amyloid-peptides-production-via-modulation-of-amyloidogenic-pathway
#20
Lan-Xue Zhao, Yan Wang, Ting Liu, Yan-Xia Wang, Hong-Zhuan Chen, Jian-Rong Xu, Yu Qiu
AIMS: β-amyloid (Aβ) aggregation and deposition play a central role in the pathogenic process of Alzheimer's disease (AD). α-Mangostin (α-M), a polyphenolic xanthone, have been shown to dissociate Aβ oligomers. In this study, we further investigated the effect of α-M on Aβ production and its molecular mechanism. METHODS: The Aβ and soluble amyloid precursor protein α (sAPPα) in culture medium of cortical neurons were measured by ELISA. The activities of α-, β-, and γ-secretases were assayed, and the interaction between α-M and β- or γ-secretases was simulated by molecular docking...
April 21, 2017: CNS Neuroscience & Therapeutics
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