% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Antonschmidt:912259,
author = {Antonschmidt, Leif and Matthes, Dirk and Dervişoğlu,
Rıza and Frieg, Benedikt and Dienemann, Christian and
Leonov, Andrei and Nimerovsky, Evgeny and Sant, Vrinda and
Ryazanov, Sergey and Giese, Armin and Schröder, Gunnar F.
and Becker, Stefan and de Groot, Bert L. and Griesinger,
Christian and Andreas, Loren B.},
title = {{T}he clinical drug candidate anle138b binds in a cavity of
lipidic α-synuclein fibrils},
journal = {Nature Communications},
volume = {13},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {FZJ-2022-05456},
pages = {5385},
year = {2022},
abstract = {Aggregation of amyloidogenic proteins is a characteristic
of multiple neurodegenerative diseases. Atomic resolution of
small molecule binding to such pathological protein
aggregates is of interest for the development of
therapeutics and diagnostics. Here we investigate the
interaction between α-synuclein fibrils and anle138b, a
clinical drug candidate for disease modifying therapy in
neurodegeneration and a promising scaffold for positron
emission tomography tracer design. We used nuclear magnetic
resonance spectroscopy and the cryogenic electron microscopy
structure of α-synuclein fibrils grown in the presence of
lipids to locate anle138b within a cavity formed between two
β-strands. We explored and quantified multiple binding
modes of the compound in detail using molecular dynamics
simulations. Our results reveal stable polar interactions
between anle138b and backbone moieties inside the tubular
cavity of the fibrils. Such cavities are common in other
fibril structures as well.},
cin = {IBI-7},
ddc = {500},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5244 - Information Processing in Neuronal Networks
(POF4-524)},
pid = {G:(DE-HGF)POF4-5244},
typ = {PUB:(DE-HGF)16},
pubmed = {36104315},
UT = {WOS:000853935100020},
doi = {10.1038/s41467-022-32797-w},
url = {https://juser.fz-juelich.de/record/912259},
}