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@ARTICLE{Ziehm:848211,
author = {Ziehm, Tamar and Buell, Alexander K. and Willbold, Dieter},
title = {{T}he role of hydrophobicity and charge of amyloid-beta
oligomer eliminating {D}-peptides in the interaction with
amyloid-beta monomers},
journal = {ACS chemical neuroscience},
volume = {9},
number = {11},
issn = {1948-7193},
address = {Washington, DC},
publisher = {ACS Publ.},
reportid = {FZJ-2018-03473},
pages = {2679-2688},
year = {2018},
abstract = {Inhibition of the self-assembly process of amyloid-beta and
even more the removal of already existing toxic amyloid-beta
assemblies represent promising therapeutic strategies
against Alzheimer´s disease. To approach this aim, we
selected a D-enantiomeric peptide by phage-display based on
the interaction with amyloid-beta monomers. This lead
compound was successfully optimized by peptide microarrays
with respect to its affinity and specificity to the target
resulting in D-peptides with both increased hydrophobicity
and net charge. Here, we present a detailed biophysical
characterization of the interactions between these optimized
D peptides and amyloid-beta monomers in comparison to the
original lead compound in order to obtain a more thorough
understanding of the physico-chemical determinants of the
interactions. Kinetics and apparent stoichiometry of complex
formation were studied using surface plasmon resonance.
Potential modes of binding to amyloid-beta were identified
and the influences of ionic strength on complex stability,
as well as on the inhibitory effect on amyloid-beta
aggregation were investigated. The results reveal a very
different mode of interaction of the optimized D-peptides
based on a combination of electrostatic and hydrophobic
interactions as compared to the mostly electrostatically
driven interaction of the lead compound. These conclusions
were supported by the thermodynamic profiles of the
interaction between optimized D-peptides and Aβ monomers,
which indicate an increase in binding entropy with respect
to the lead compound.},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {553 - Physical Basis of Diseases (POF3-553)},
pid = {G:(DE-HGF)POF3-553},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29893543},
UT = {WOS:000451496200018},
doi = {10.1021/acschemneuro.8b00132},
url = {https://juser.fz-juelich.de/record/848211},
}