Home > Publications database > Complementarity determining regions of an anti-prion protein scFv fragment orchestrate conformation specificity and antiprion activity > print

001     2682
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024 7 _ |2 pmid
|a pmid:18973947
024 7 _ |2 DOI
|a 10.1016/j.molimm.2008.07.023
024 7 _ |2 WOS
|a WOS:000263429500004
024 7 _ |a altmetric:21801073
|2 altmetric
037 _ _ |a PreJuSER-2682
041 _ _ |a eng
082 _ _ |a 570
084 _ _ |2 WoS
|a Biochemistry & Molecular Biology
084 _ _ |2 WoS
|a Immunology
100 1 _ |0 P:(DE-HGF)0
|a Müller-Schiffmann, A.
|b 0
245 _ _ |a Complementarity determining regions of an anti-prion protein scFv fragment orchestrate conformation specificity and antiprion activity
260 _ _ |a Oxford
|b Pergamon Press
|c 2009
300 _ _ |a 532 - 540
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |0 20061
|a Molecular Immunology
|v 46
|x 0161-5890
|y 4
500 _ _ |a This work was funded by a grant from the Forschungskommission of the University of Dusseldorf Medical School (to R.L.), a grant from the VW foundation (to CX and S.S.), a grant from the TSE-Program Baden-Wuerttemberg (729.59-7/1; to L.S.), a grant from the DFG (GRK1033; to CK), and a grant from the FP6, EU Research Commission Anteprion (LSHB-C7-2006-019090; to CX and L.S.).
520 _ _ |a The prion protein, PrP, exists in several stable conformations, with the presence of one conformation, PrP(Sc), associated with transmissible neurodegenerative diseases. Targeting PrP by high-affinity ligands has been proven to be an effective way of preventing peripheral prion infections. Here, we have generated bacterially expressed single chain fragments of the variable domains (scFv) of a monoclonal antibody in Escherichia coli, originally raised against purified PrP(Sc) that recognizes both PrP(C) and PrP(Sc). This scFv fragment had a dissociation constant (K(D)) with recombinant PrP of 2 nM and cleared prions in ScN2a cells at 4 nM, as demonstrated by a mouse prion bioassay. A peptide corresponding to the complementarity determining region 3 of the heavy chain (CDR3H) selectively bound PrP(Sc) but had lost antiprion activity. However, synthesis and application of an improved peptide mimicking side chain topology of CDR3H while exhibiting increased protease resistance, a retro-inverso d-peptide of CDR3H, still bound PrP(Sc) and reinstated antiprion activity. We conclude that (1) scFvW226 is so far the smallest polypeptide with bioassay confirmed antiprion activity, and (2) differential conformation specificity and bioactivity can be regulated by orchestrating the participation of different CDRs.
536 _ _ |0 G:(DE-Juel1)FUEK409
|2 G:(DE-HGF)
|a Funktion und Dysfunktion des Nervensystems
|c P33
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Amino Acid Sequence
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Antibody Affinity: immunology
650 _ 2 |2 MeSH
|a Cell Line
650 _ 2 |2 MeSH
|a Complementarity Determining Regions: immunology
650 _ 2 |2 MeSH
|a Complementarity Determining Regions: metabolism
650 _ 2 |2 MeSH
|a Mice
650 _ 2 |2 MeSH
|a Mice, Knockout
650 _ 2 |2 MeSH
|a Molecular Sequence Data
650 _ 2 |2 MeSH
|a Peptides: chemistry
650 _ 2 |2 MeSH
|a Peptides: immunology
650 _ 2 |2 MeSH
|a Peptides: metabolism
650 _ 2 |2 MeSH
|a PrPC Proteins: immunology
650 _ 2 |2 MeSH
|a PrPC Proteins: metabolism
650 _ 2 |2 MeSH
|a PrPSc Proteins: immunology
650 _ 2 |2 MeSH
|a PrPSc Proteins: metabolism
650 _ 2 |2 MeSH
|a Protein Conformation
650 _ 7 |0 0
|2 NLM Chemicals
|a Complementarity Determining Regions
650 _ 7 |0 0
|2 NLM Chemicals
|a Peptides
650 _ 7 |0 0
|2 NLM Chemicals
|a PrPC Proteins
650 _ 7 |0 0
|2 NLM Chemicals
|a PrPSc Proteins
650 _ 7 |2 WoSType
|a J
653 2 0 |2 Author
|a Prions
653 2 0 |2 Author
|a Monoclonal antibody
653 2 0 |2 Author
|a Conformation specificity
653 2 0 |2 Author
|a Complementarity determining regions
653 2 0 |2 Author
|a Recombinant antibodies
653 2 0 |2 Author
|a Retro-inverso D-peptides
700 1 _ |0 P:(DE-HGF)0
|a Petsch, B.
|b 1
700 1 _ |0 P:(DE-Juel1)VDB72260
|a Leliveld, S. R.
|b 2
|u FZJ
700 1 _ |0 P:(DE-HGF)0
|a Muyrers, J.
|b 3
700 1 _ |0 P:(DE-HGF)0
|a Salwierz, A.
|b 4
700 1 _ |0 P:(DE-HGF)0
|a Mangels, Ch.
|b 5
700 1 _ |0 P:(DE-HGF)0
|a Schwarzinger, St.
|b 6
700 1 _ |0 P:(DE-HGF)0
|a Riesner, D.
|b 7
700 1 _ |0 P:(DE-HGF)0
|a Stitz, L.
|b 8
700 1 _ |0 P:(DE-HGF)0
|a Korth, C.
|b 9
773 _ _ |0 PERI:(DE-600)2013448-4
|a 10.1016/j.molimm.2008.07.023
|g Vol. 46, p. 532 - 540
|p 532 - 540
|q 46<532 - 540
|t Molecular immunology
|v 46
|x 0161-5890
|y 2009
856 7 _ |u http://dx.doi.org/10.1016/j.molimm.2008.07.023
909 C O |o oai:juser.fz-juelich.de:2682
|p VDB
913 1 _ |0 G:(DE-Juel1)FUEK409
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914 1 _ |y 2010
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |0 I:(DE-Juel1)VDB805
|d 31.12.2008
|g INB
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981 _ _ |a I:(DE-Juel1)ISB-2-20090406
981 _ _ |a I:(DE-Juel1)ICS-6-20110106

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