This title appears in the Scientific Report :
2016
Please use the identifier:
http://dx.doi.org/10.1021/acsnano.6b02627 in citations.
Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation
Therapeutically 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...
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Personal Name(s): | Streich, Carmen |
---|---|
Akkari, Laura / Decker, Christina / Bormann, Jenny / Rehbock, Christoph / Müller-Schiffmann, Andreas / Niemeyer, Felix Carlsson / Nagel-Steger, Luitgard / Willbold, Dieter / Sacca, Barbara / Korth, Carsten / Schrader, Thomas (Corresponding author) / Barcikowski, Stephan | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | ACS nano, 10 (2016) 8, S. 7582-7597 |
Imprint: |
Washington, DC
Soc.
2016
|
PubMed ID: |
27404114 |
DOI: |
10.1021/acsnano.6b02627 |
Document Type: |
Journal Article |
Research Program: |
Physical Basis of Diseases |
Publikationsportal JuSER |
Therapeutically 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. |