排序方式: 共有73条查询结果,搜索用时 0 毫秒
71.
Alexandre Chappard Dr. Craig Leighton Dr. Rebecca S. Saleeb Kiani Jeacock Dr. Sarah R. Ball Katie Morris Owen Kantelberg Dr. Ji-Eun Lee Dr. Elsa Zacco Prof. Dr. Annalisa Pastore Prof. Dr. Margaret Sunde Dr. David J. Clarke Dr. Patrick Downey Prof. Dr. Tilo Kunath Dr. Mathew H. Horrocks 《Angewandte Chemie (International ed. in English)》2023,62(15):e202216771
Protein misfolding and aggregation into oligomeric and fibrillar structures is a common feature of many neurogenerative disorders. Single-molecule techniques have enabled characterization of these lowly abundant, highly heterogeneous protein aggregates, previously inaccessible using ensemble averaging techniques. However, they usually rely on the use of recombinantly-expressed labeled protein, or on the addition of amyloid stains that are not protein-specific. To circumvent these challenges, we have made use of a high affinity antibody labeled with orthogonal fluorophores combined with fast-flow microfluidics and single-molecule confocal microscopy to specifically detect α-synuclein, the protein associated with Parkinson's disease. We used this approach to determine the number and size of α-synuclein aggregates down to picomolar concentrations in biologically relevant samples. 相似文献
72.
Abdalghani Daaoub James M. F. Morris Vanessa A. Béland Paul Demay-Drouhard Amaar Hussein Simon J. Higgins Hatef Sadeghi Richard J. Nichols Andrea Vezzoli Thomas Baumgartner Sara Sangtarash 《Angewandte Chemie (International ed. in English)》2023,62(24):e202302150
Most studies in molecular electronics focus on altering the molecular wire backbone to tune the electrical properties of the whole junction. However, it is often overlooked that the chemical structure of the groups anchoring the molecule to the metallic electrodes influences the electronic structure of the whole system and, therefore, its conductance. We synthesised electron-accepting dithienophosphole oxide derivatives and fabricated their single-molecule junctions. We found that the anchor group has a dramatic effect on charge-transport efficiency: in our case, electron-deficient 4-pyridyl contacts suppress conductance, while electron-rich 4-thioanisole termini promote efficient transport. Our calculations show that this is due to minute changes in charge distribution, probed at the electrode interface. Our findings provide a framework for efficient molecular junction design, especially valuable for compounds with strong electron withdrawing/donating backbones. 相似文献
73.
María del Carmen Fernández-Ramírez Kevin Kan-Shing Ng Margarita Menéndez Douglas V. Laurents Rubén Hervás Mariano Carrión-Vázquez 《Angewandte Chemie (International ed. in English)》2023,62(19):e202209252
Understanding early amyloidogenesis is key to rationally develop therapeutic strategies. Tau protein forms well-characterized pathological deposits but its aggregation mechanism is still poorly understood. Using single-molecule force spectroscopy based on a mechanical protection strategy, we studied the conformational landscape of the monomeric tau repeat domain (tau-RD244-368). We found two sets of conformational states, whose frequency is influenced by mutations and the chemical context. While pathological mutations Δ280K and P301L and a pro-amyloidogenic milieu favored expanded conformations and destabilized local structures, an anti-amyloidogenic environment promoted a compact ensemble, including a conformer whose topology might mask two amyloidogenic segments. Our results reveal that to initiate aggregation, monomeric tau-RD244-368 decreases its polymorphism adopting expanded conformations. This could account for the distinct structures found in vitro and across tauopathies. 相似文献