000835512 001__ 835512
000835512 005__ 20230207130453.0
000835512 0247_ $$2CORDIS$$aG:(EU-Grant)726368$$d726368
000835512 0247_ $$2CORDIS$$aG:(EU-Call)ERC-2016-COG$$dERC-2016-COG
000835512 0247_ $$2originalID$$acorda__h2020::726368
000835512 035__ $$aG:(EU-Grant)726368
000835512 150__ $$aControl of amyloid formation via beta-hairpin molecular recognition features$$y2017-06-01 - 2023-02-28
000835512 371__ $$aHeinrich Heine University Düsseldorf$$bHHU$$dGermany$$ehttp://www.uni-duesseldorf.de/home/en/home.html$$vCORDIS
000835512 372__ $$aERC-2016-COG$$s2017-06-01$$t2023-02-28
000835512 450__ $$aBETACONTROL$$wd$$y2017-06-01 - 2023-02-28
000835512 5101_ $$0I:(DE-588b)5098525-5$$2CORDIS$$aEuropean Union
000835512 680__ $$aThe 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.
000835512 909CO $$ooai:juser.fz-juelich.de:835512$$pauthority$$pauthority:GRANT
000835512 970__ $$aoai:dnet:corda__h2020::50ac88dcdad3f2d00f9bceadebee3960
000835512 980__ $$aG
000835512 980__ $$aCORDIS
000835512 980__ $$aAUTHORITY