Journal Article FZJ-2017-01157

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Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation

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2016
Soc. Washington, DC

ACS nano 10(8), 7582-7597 () [10.1021/acsnano.6b02627]

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Abstract: 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.

Classification:

Contributing Institute(s):
  1. Strukturbiochemie (ICS-6)
Research Program(s):
  1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2016
Database coverage:
Medline ; Current Contents - Physical, Chemical and Earth Sciences ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; No Authors Fulltext ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection
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Document types > Articles > Journal Article
Institute Collections > IBI > IBI-7
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ICS > ICS-6
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 Record created 2017-01-27, last modified 2021-01-29


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