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@ARTICLE{Brown:909359,
author = {Brown, Hawley and Chung, Mia and Üffing, Alina and
Batistatou, Nefeli and Tsang, Tiffany and Doskocil, Samantha
and Mao, Weiqun and Willbold, Dieter and Bast, Robert C. and
Lu, Zhen and Weiergräber, Oliver H. and Kritzer, Joshua A.},
title = {{S}tructure-{B}ased {D}esign of {S}tapled {P}eptides {T}hat
{B}ind {GABARAP} and {I}nhibit {A}utophagy},
journal = {Journal of the American Chemical Society},
volume = {144},
number = {32},
issn = {0002-7863},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2022-03149},
pages = {14687 - 14697},
year = {2022},
abstract = {The LC3/GABARAP family of proteins are involved in nearly
every stage of autophagy. Inhibition of LC3/GABARAP proteins
is a promising approach to blocking autophagy, which
sensitizes advanced cancers to DNA-damaging chemotherapy.
Here, we report the structure-based design of stapled
peptides that inhibit GABARAP with nanomolar affinities.
Small changes in staple structure produced stapled peptides
with very different binding modes and functional differences
in LC3/GABARAP paralog selectivity, ranging from highly
GABARAP-specific to broad inhibition of both subfamilies.
The stapled peptides exhibited considerable cytosolic
penetration and resistance to biological degradation. They
also reduced autophagic flux in cultured ovarian cancer
cells and sensitized ovarian cancer cells to cisplatin.
These small, potent stapled peptides represent promising
autophagy-modulating compounds that can be developed as
novel cancer therapeutics and novel mediators of targeted
protein degradation.},
cin = {IBI-7},
ddc = {540},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524) / SFB 1208 B02 - Spezifische Rollen von Atg8s im
Vesikeltransport (B02) (289554527)},
pid = {G:(DE-HGF)POF4-5241 / G:(GEPRIS)289554527},
typ = {PUB:(DE-HGF)16},
pubmed = {35917476},
UT = {WOS:000836234100001},
doi = {10.1021/jacs.2c04699},
url = {https://juser.fz-juelich.de/record/909359},
}