Peptide NMHRYPNQ of the cellular prion protein (PrP(C)) inhibits aggregation and is a potential key for understanding prion-prion interactions.
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.
Rehders
Dirk
D
Department of Chemistry, University of Hamburg, Germany.
Claasen
Birgit
B
Redecke
Lars
L
Buschke
Alexander
A
Reibe
Caroline
C
Jehmlich
Nico
N
von Bergen
Martin
M
Betzel
Christian
C
Meyer
Bernd
B
D004353:Drug Evaluation, Preclinical; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000494:pharmacology*; D011328:Prions / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D019151:Peptide Library; D010455:Peptides; D011328:Prions