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@ARTICLE{Rehders:94432,
author = {Rehders, D. and Claasen, B. and Redecke, L. and Buschke, A.
and Reibe, C. and Jehmlich, N. and von Bergen, M. and
Betzel, C. and Meyer, B. and DESY},
title = {{P}eptide {NMHRYPNQ} of the cellular prion protein
({P}r{P}({C})) inhibits aggregation and is a potential key
for understanding prion-prion interactions.},
journal = {Journal of molecular biology},
volume = {392},
issn = {0022-2836},
address = {Amsterdam [u.a.]},
publisher = {Elsevier},
reportid = {PHPPUBDB-19404},
pages = {198-207},
year = {2009},
note = {© Elsevier Ltd.; Post referee fulltext in progress 2;
Embargo 12 months from publication},
abstract = {Pathogenesis of transmissible spongiform encephalopathies
is correlated with a conversion of the normal cellular form
of the prion protein (PrP(C)) into the abnormal isoform
(scrapie form of PrP). Contact of the normal PrP with its
abnormal isoform, the scrapie form of PrP, induces the
transformation. Knowledge of molecules that inhibit such
contacts leads to an understanding of the mechanism of the
aggregation, and these molecules may serve as leads for
drugs against transmissible spongiform encephalopathies.
Therefore, we screened a synthetic octapeptide library of
the globular domain of the human PrP(C) for binding affinity
to PrP(C). Two fragments with binding affinity,
149YYRENMHR156 and 153NMHRYPNQ160, were identified with K(d)
values of 21 and 25 microM, respectively. A 10-fold excess
of peptide 153NMHRYPNQ160 inhibits aggregation of the PrP by
$99\%.$ NMR and mass spectrometry showed that the binding
region of the peptide 153NMHRYPNQ160 is located at helix 3
of the PrP.},
keywords = {Drug Evaluation, Preclinical / Humans / Kinetics / Magnetic
Resonance Spectroscopy / Mass Spectrometry / Models,
Molecular / Peptide Library / Peptides: pharmacology /
Prions: antagonists $\&$ inhibitors / Prions: metabolism /
Protein Binding / Protein Structure, Tertiary / Peptide
Library (NLM Chemicals) / Peptides (NLM Chemicals) / Prions
(NLM Chemicals)},
cin = {EMBL(-2012)},
ddc = {570},
cid = {$I:(DE-H253)EMBL_-2012_-20130307$},
pnm = {DORIS Beamline D1.2 (POF1-550)},
pid = {G:(DE-H253)POF1-D1.2-20130405},
experiment = {EXP:(DE-H253)D-D1.2-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:19607841},
UT = {WOS:000270123600016},
doi = {10.1016/j.jmb.2009.07.014},
url = {https://bib-pubdb1.desy.de/record/94432},
}