TY  - JOUR
AU  - Zhang, Tao
AU  - Loschwitz, Jennifer
AU  - Strodel, Birgit
AU  - Nagel-Steger, Luitgard
AU  - Willbold, Dieter
TI  - Interference with Amyloid-β Nucleation by Transient Ligand Interaction
JO  - Molecules
VL  - 24
IS  - 11
SN  - 1420-3049
CY  - Basel
PB  - MDPI
M1  - FZJ-2019-03184
SP  - 2129 -
PY  - 2019
AB  - Amyloid-β peptide (Aβ) is an intrinsically disordered protein (IDP) associated with Alzheimer’s disease. The structural flexibility and aggregation propensity of Aβ pose major challenges for elucidating the interaction between Aβ monomers and ligands. All-D-peptides consisting solely of D-enantiomeric amino acid residues are interesting drug candidates that combine high binding specificity with high metabolic stability. Here we characterized the interaction between the 12-residue all-D-peptide D3 and Aβ42 monomers, and how the interaction influences Aβ42 aggregation. We demonstrate for the first time that D3 binds to Aβ42 monomers with submicromolar affinities. These two highly unstructured molecules are able to form complexes with 1:1 and other stoichiometries. Further, D3 at substoichiometric concentrations effectively slows down the β-sheet formation and Aβ42 fibrillation by modulating the nucleation process. The study provides new insights into the molecular mechanism of how D3 affects Aβ assemblies and contributes to our knowledge on the interaction between two IDPs.
LB  - PUB:(DE-HGF)16
C6  - pmid:31195746
UR  - <Go to ISI:>//WOS:000472631000102
DO  - DOI:10.3390/molecules24112129
UR  - https://juser.fz-juelich.de/record/863067
ER  -