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@ARTICLE{Orr:858403,
author = {Orr, Asuka A. and Shaykhalishahi, Hamed and Mirecka, Ewa A.
and Jonnalagadda, Sai Vamshi R. and Hoyer, Wolfgang and
Tamamis, Phanourios},
title = {{E}lucidating the multi-targeted anti-amyloid activity and
enhanced islet amyloid polypeptide binding of β-wrapins},
journal = {Computers $\&$ chemical engineering},
volume = {116},
issn = {0098-1354},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {FZJ-2018-07289},
pages = {322 - 332},
year = {2018},
abstract = {β-wrapins are engineered binding proteins stabilizing the
β-hairpin conformations of amyloidogenic proteins islet
amyloid polypeptide (IAPP), amyloid-β, and α-synuclein,
thus inhibiting their amyloid propensity. Here, we use
computational and experimental methods to investigate the
molecular recognition of IAPP by β-wrapins. We show that
the multi-targeted, IAPP, amyloid-β, and α-synuclein,
binding properties of β-wrapins originate mainly from
optimized interactions between β-wrapin residues and sets
of residues in the three amyloidogenic proteins with similar
physicochemical properties. Our results suggest that IAPP is
a comparatively promiscuous β-wrapin target, probably due
to the low number of charged residues in the IAPP β-hairpin
motif. The sub-micromolar affinity of β-wrapin HI18,
specifically selected against IAPP, is achieved in part by
salt-bridge formation between HI18 residue Glu10 and the
IAPP N-terminal residue Lys1, both located in the flexible
N-termini of the interacting proteins. Our findings provide
insights towards developing novel protein-based single- or
multi-targeted therapeutics.},
cin = {ICS-6},
ddc = {660},
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:30405276},
UT = {WOS:000448410000023},
doi = {10.1016/j.compchemeng.2018.02.013},
url = {https://juser.fz-juelich.de/record/858403},
}