Universtitat Duisburg Essen

Essen, Germany

Universtitat Duisburg Essen

Essen, Germany

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Streich C.,University of Duisburg - Essen | Akkari L.,University of Duisburg - Essen | Decker C.,Heinrich Heine University Düsseldorf | Bormann J.,Universtitat Duisburg Essen | And 11 more authors.
ACS Nano | Year: 2016

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. © 2016 American Chemical Society.


Nickel S.,Universtitat Duisburg Essen | Nickel P.,Universtitat Duisburg Essen | Hellmert M.,Universtitat Duisburg Essen | Ernst S.,Universtitat Duisburg Essen | And 5 more authors.
Bioorganic and Medicinal Chemistry | Year: 2015

Scaffolds of natural products represent promising starting points for the development of focused compound libraries. Here, we describe the development of a synthetic route to a compound library based on the hexahydropyrrolo indole (HPI) scaffold, the denoting structural motif of the HPI natural product family. To this end, a two-step approach consisting of a batch synthesis of an advanced functionalizable HPI intermediate followed by the establishment of reaction conditions that allow derivatization of this scaffold at three different positions is described. Subsequently, the optimized methods were applied to the synthesis of a 276-member library. © 2015 Elsevier Ltd. All rights reserved.


PubMed | Universtitat Duisburg Essen, Heinrich Heine University Düsseldorf, University of Dusseldorf Medical School and University of Duisburg - Essen
Type: Journal Article | Journal: ACS nano | Year: 2016

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 A-specific small molecules to inhibit A peptide aggregation into fibrils in vitro. The interactions of bare NPs, free ligands, and NP-bound ligands with A are comprehensively studied via physicochemical methods (spectroscopy, microscopy, immunologic tests) and cell assays. Reduction of thioflavin T fluorescence, as an indicator for -sheet content, and inhibition of cellular A 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 Alzheimers disease.


PubMed | Universtitat Duisburg Essen and Sygnature Discovery
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

Scaffolds of natural products represent promising starting points for the development of focused compound libraries. Here, we describe the development of a synthetic route to a compound library based on the hexahydropyrrolo indole (HPI) scaffold, the denoting structural motif of the HPI natural product family. To this end, a two-step approach consisting of a batch synthesis of an advanced functionalizable HPI intermediate followed by the establishment of reaction conditions that allow derivatization of this scaffold at three different positions is described. Subsequently, the optimized methods were applied to the synthesis of a 276-member library.

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