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000826950 1001_ $$0P:(DE-HGF)0$$aStreich, Carmen$$b0
000826950 245__ $$aCharacterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
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000826950 520__ $$aTherapeutically active small molecules represent promising nonimmunogenic alternatives to antibodies for specifically targeting disease-relevant receptors. However, a potential drawback compared to antibody–antigen interactions may be the lower affinity of small molecules toward receptors. Here, we overcome this low-affinity problem by coating the surface of nanoparticles (NPs) with multiple ligands. Specifically, we explored the use of gold and platinum nanoparticles to increase the binding affinity of Aβ-specific small molecules to inhibit Aβ peptide aggregation into fibrils in vitro. The interactions of bare NPs, free ligands, and NP-bound ligands with Aβ are comprehensively studied via physicochemical methods (spectroscopy, microscopy, immunologic tests) and cell assays. Reduction of thioflavin T fluorescence, as an indicator for β-sheet content, and inhibition of cellular Aβ excretion are even more effective with NP-bound ligands than with the free ligands. The results from this study may have implications in the development of therapeutics for treating Alzheimer’s disease.
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000826950 7001_ $$0P:(DE-HGF)0$$aAkkari, Laura$$b1
000826950 7001_ $$0P:(DE-Juel1)162438$$aDecker, Christina$$b2
000826950 7001_ $$0P:(DE-HGF)0$$aBormann, Jenny$$b3
000826950 7001_ $$0P:(DE-HGF)0$$aRehbock, Christoph$$b4
000826950 7001_ $$0P:(DE-HGF)0$$aMüller-Schiffmann, Andreas$$b5
000826950 7001_ $$0P:(DE-HGF)0$$aNiemeyer, Felix Carlsson$$b6
000826950 7001_ $$0P:(DE-Juel1)162443$$aNagel-Steger, Luitgard$$b7$$ufzj
000826950 7001_ $$0P:(DE-Juel1)132029$$aWillbold, Dieter$$b8$$ufzj
000826950 7001_ $$0P:(DE-HGF)0$$aSacca, Barbara$$b9
000826950 7001_ $$0P:(DE-HGF)0$$aKorth, Carsten$$b10
000826950 7001_ $$0P:(DE-HGF)0$$aSchrader, Thomas$$b11$$eCorresponding author
000826950 7001_ $$0P:(DE-HGF)0$$aBarcikowski, Stephan$$b12
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