Journal Article

PHPPUBDB-19404

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Peptide NMHRYPNQ of the cellular prion protein (PrP(C)) inhibits aggregation and is a potential key for understanding prion-prion interactions.

Rehders, D. ; Claasen, B. ; Redecke, L. ; Buschke, A. ; Reibe, C. ; Jehmlich, N. ; von Bergen, M. ; Betzel, C. ; Meyer, B. ; DESY

2009
Elsevier Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.jmb.2009.07.014

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.

Keyword(s): Drug Evaluation, Preclinical (MeSH) ; Humans (MeSH) ; Kinetics (MeSH) ; Magnetic Resonance Spectroscopy (MeSH) ; Mass Spectrometry (MeSH) ; Models, Molecular (MeSH) ; Peptide Library (MeSH) ; Peptides: pharmacology (MeSH) ; Prions: antagonists & inhibitors (MeSH) ; Prions: metabolism (MeSH) ; Protein Binding (MeSH) ; Protein Structure, Tertiary (MeSH) ; Peptide Library ; Peptides ; Prions

Note: © Elsevier Ltd.; Post referee fulltext in progress 2; Embargo 12 months from publication

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Contributing Institute(s):

1. EMBL (EMBL(-2012))

Research Program(s):

1. DORIS Beamline D1.2 (POF1-550) (POF1-550)

Experiment(s):

1. DORIS Beamline D1.2 (DORIS III)

Appears in the scientific report 2009

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Database coverage:
; JCR ; No Author Disambiguation ; No Authors Fulltext ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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