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91.
Sandra Rocha Rumen Krastev Andreas F Thünemann M Carmo Pereira Helmuth M?hwald Gerald Brezesinski 《Chemphyschem》2005,6(12):2527-2534
The adsorption of amyloid beta-peptide at hydrophilic and hydrophobic modified silicon-liquid interfaces was characterized by neutron reflectometry. Distinct polymeric films were used to obtain noncharged (Formvar), negatively (sodium poly(styrene sulfonate)) and positively charged (poly(allylamine hydrochloride)) hydrophilic as well as hydrophobic surfaces (polystyrene and a polysiloxane-dodecanoic acid complex). Amyloid beta-peptide was found to adsorb at positively charged hydrophilic and hydrophobic surfaces, whereas no adsorbed layer was detected on hydrophilic noncharged and negatively charged films. The peptide adsorbed at the positively charged film as patches, which were dispersed on the surface, whereas a uniform layer was observed at hydrophobic surfaces. The thickness of the adsorbed peptide layer was estimated to be approximately 20 A. The peptide formed a tightly packed layer, which did not contain water. These studies provide information about the affinity of the amyloid beta-peptide to different substrates in aqueous solution and suggest that the amyloid fibril formation may be driven by interactions with surfaces. 相似文献
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Dr. Camilla Gustafsson Dr. Hamid Shirani Petter Leira Dr. Dirk R. Rehn Dr. Mathieu Linares Prof. K. Peter R. Nilsson Prof. Patrick Norman Prof. Mikael Lindgren 《Chemphyschem》2021,22(3):323-335
Anionic pentameric thiophene acetates can be used for fluorescence detection and diagnosis of protein amyloid aggregates. Replacing the central thiophene unit by benzothiadiazole (BTD) or quinoxaline (QX) leads to large emission shifts and basic spectral features have been reported [Chem. Eur. J. 2015 , 21, 15133-13137]. Here we present new detailed experimental results of solvent effects, time-resolved fluorescence and examples employing multi-photon microscopy and lifetime imaging. Quantum chemical response calculations elucidate how the introduction of the BTD/QX groups changes the electronic states and emissions. The dramatic red-shift follows an increased conjugation and quinoid character of the π-electrons of the thiophene backbone. An efficient charge transfer in the excited states S1 and S2 compared to the all-thiophene analogue makes these more sensitive to the polarity and quenching by the solvent. Taken together, the results guide in the interpretation of images of stained Alzheimer disease brain sections employing advanced fluorescence microscopy and lifetime imaging, and can aid in optimizing future fluorescent ligand development. 相似文献
95.
Ivan A. Zanyatkin Yulia Yu. Stroylova Aleksandra K. Melnikova Ali Akbar Moosavi-Movahedi Ali Akbar Saboury Thomas Haertle Vladimir I. Muronetz 《Mendeleev Communications》2021,31(1):73-75
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Inhibition of Cu‐Amyloid‐β by using Bifunctional Peptides with β‐Sheet Breaker and Chelator Moieties
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Dr. Andrea Antosova Dr. Zuzana Bednarikova Dr. Martina Koneracka Dr. Iryna Antal Dr. Jozef Marek Dr. Martina Kubovcikova Dr. Vlasta Zavisova Dr. Alena Jurikova Dr. Zuzana Gazova 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(31):7501-7514
Nanoparticles have great potential to be used in various biomedical applications, including therapy or diagnosis of amyloid-related diseases. The physical and chemical properties of iron oxide superparamagnetic nanoparticles (MNPs) functionalized with different amino acids (AAs), namely, with lysine (Lys), glycine (Gly), or tryptophan (Trp), have been characterized. The cytotoxicity of nanoparticles and their effect on amyloid fibrillization of lysozymes in vitro was also verified. The AA-MNPs under study are nontoxic to human SHSY5Y neuroblastoma cells. Moreover, the AA-MNPs were able to significantly inhibit lysozyme amyloid fibrillization and destroy amyloid fibrils. Kinetic studies revealed that the presence of AA-MNPs affected lysozyme fibrillization, namely, the lag phase and steady-state phase of the growth curves. The most effective activities were observed for Trp-MNPs, which revealed the importance of aromatic rings in the structure of AAs used as coating agents. The obtained results indicate the possible application of these AA-MNPs in the treatment of amyloid diseases associated with lysozyme or other amyloidogenic proteins. 相似文献
99.
Naoki KANEKO Rie YAMAMOTO Taka-Aki SATO Koichi TANAKA 《Proceedings of the Japan Academy. Series B, Physical and biological sciences》2014,90(3):104-117
Proteolytic processing of the amyloid precursor protein (APP) by β-secretase and γ-secretase leads to the generation and deposition of amyloid β (Aβ) in Alzheimer’s disease (AD). N-terminally or C-terminally truncated Aβ variants have been found in human cerebrospinal fluid and cultured cell media using immunoprecipitation and mass spectrometry. Unfortunately, the profile of plasma Aβ variants has not been revealed due to the difficulty of isolating Aβ from plasma. We present here for the first time studies of Aβ and related peptides in human plasma. Twenty-two Aβ-related peptides including novel peptides truncated before the β-secretase site were detected in human plasma and 20 of the peptides were identified by tandem mass spectrometry. Using an internal standard, we developed a quantitative assay for the Aβ-related peptides and demonstrated plasma dilution linearity and the precision required for their quantitation. The present method should enhance the understanding of APP processing and clearance in AD progression. 相似文献
100.
Jun Seok Kim Hee-Sung Ahn Soo Min Cho Ji Eun Lee YoungSoo Kim Cheolju Lee 《Analytica chimica acta》2014
Amyloid-β (Aβ) in human plasma was detected and quantified by an antibody-free method, selected reaction monitoring mass spectrometry (SRM-MS) in the current study. Due to its low abundance, SRM-based quantification in 10 μL plasma was a challenge. Prior to SRM analysis, human plasma proteins as a whole were digested by trypsin and high pH reversed-phase liquid chromatography (RPLC) was used to fractionate the tryptic digests and to collect peptides, Aβ1–5, Aβ6–16, Aβ17–28 and Aβ29–40(42) of either Aβ1–40 or Aβ1–42. Among those peptides, Aβ17–28 was selected as a surrogate to measure the total Aβ level. Human plasma samples obtained from triplicate sample preparations were analyzed, obtaining 4.20 ng mL−1 with a CV of 25.3%. Triplicate measurements for each sample preparation showed CV of <5%. Limit of quantification was obtained as 132 pM, which corresponded to 570 pg mL−1 of Aβ1–40. Until now, most quantitative measurements of Aβ in plasma or cerebrospinal fluid have required antibody-based immunoassays. Since quantification of Aβ by immunoassays is highly dependent on the extent of epitope exposure due to aggregation or plasma protein binding, it is difficult to accurately measure the actual concentration of Aβ in plasma. Our diagnostic method based on SRM using a surrogate peptide of Aβ is promising in that actual amounts of total Aβ can be measured regardless of the conformational status of the biomarker. 相似文献