Control of amyloid formation via beta-hairpin molecular recognition features

Projektinformationen

BETACONTROL

ID Finanzhilfevereinbarung: 726368

DOI 10.3030/726368

Abgeschlossenes Projekt

EK-Unterschriftsdatum 16 Mai 2017

Startdatum 1 Juni 2017

Enddatum 28 Februar 2023

Finanziert unter

• EXCELLENT SCIENCE - European Research Council (ERC)

Gesamtkosten € 1 920 697,00

EU-Beitrag € 1 920 697,00

Koordiniert durch

HEINRICH-HEINE-UNIVERSITAET DUESSELDORF
Germany

Ziel

The aggregation of proteins into amyloid fibrils is involved in various diseases which place a high burden on patients, families, caregivers, and healthcare systems, including Alzheimer’s disease, Parkinson’s disease and type 2 diabetes. While the therapeutic potential of the inhibition of amyloid formation and spreading has been recognized, there is a lack of effective strategies targeting the early steps of the aggregation reaction.

In BETACONTROL, I want to establish a structure-guided approach to the control of amyloid formation and spreading. I will develop small molecule and polypeptide-based ligands that interfere with the initial phases of amyloid formation and thereby suppress any toxic oligomeric or fibrillar assemblies. The ligands will target beta-hairpin molecular recognition features, which I found to be readily accessible in disease-related amyloidogenic proteins. Targeting beta-hairpins enables retardation of protein aggregation by substoichiometric amounts of the ligand, affording inhibition of amyloid formation at low compound concentrations. As the strategy addresses the common propensity of amyloidogenic proteins to adopt beta-structure, it will be applicable to a wide range of proteins associated with various diseases.

BETACONTROL will yield molecular-level insight into the mechanistic basis of amyloid formation and spreading. Furthermore, it will elucidate the significance of beta-hairpins as molecular recognition features in intrinsically disordered proteins (IDPs) and highlight the applicability of these features as targets for interference with protein-protein interactions of IDPs. Ultimately, BETACONTROL will provide a novel therapeutic approach to a range of devastating diseases.

Wissenschaftliches Gebiet

• natural sciences › biological sciences › biochemistry › biomolecules › proteins › proteomics
• medical and health sciences › basic medicine › neurology › dementia › alzheimer
• medical and health sciences › clinical medicine › endocrinology › diabetes
• medical and health sciences › basic medicine › neurology › parkinson

Programm/Programme

• H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme

Thema/Themen

• ERC-2016-COG - ERC Consolidator Grant

Aufforderung zur Vorschlagseinreichung

ERC-2016-COG

Finanzierungsplan

ERC-COG - Consolidator Grant

Gastgebende Einrichtung

HEINRICH-HEINE-UNIVERSITAET DUESSELDORF

• Netto-EU-Beitrag: € 1 920 697,00
• Adresse: UNIVERSITAETSSTRASSE 1 ; 40225 Dusseldorf ; Deutschland
• Region: Nordrhein-Westfalen › Düsseldorf › Düsseldorf, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 920 697,00

Begünstigte (1)

HEINRICH-HEINE-UNIVERSITAET DUESSELDORF

Deutschland

• Netto-EU-Beitrag: € 1 920 697,00
• Adresse: UNIVERSITAETSSTRASSE 1 ; 40225 Dusseldorf
• Region: Nordrhein-Westfalen › Düsseldorf › Düsseldorf, Kreisfreie Stadt
• Aktivitätstyp: Higher or Secondary Education Establishments
• Gesamtkosten: € 1 920 697,00