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000002682 0247_ $$2DOI$$a10.1016/j.molimm.2008.07.023
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000002682 084__ $$2WoS$$aBiochemistry & Molecular Biology
000002682 084__ $$2WoS$$aImmunology
000002682 1001_ $$0P:(DE-HGF)0$$aMüller-Schiffmann, A.$$b0
000002682 245__ $$aComplementarity determining regions of an anti-prion protein scFv fragment orchestrate conformation specificity and antiprion activity
000002682 260__ $$aOxford$$bPergamon Press$$c2009
000002682 300__ $$a532 - 540
000002682 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article
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000002682 3367_ $$2DRIVER$$aarticle
000002682 440_0 $$020061$$aMolecular Immunology$$v46$$x0161-5890$$y4
000002682 500__ $$aThis work was funded by a grant from the Forschungskommission of the University of Dusseldorf Medical School (to R.L.), a grant from the VW foundation (to CX and S.S.), a grant from the TSE-Program Baden-Wuerttemberg (729.59-7/1; to L.S.), a grant from the DFG (GRK1033; to CK), and a grant from the FP6, EU Research Commission Anteprion (LSHB-C7-2006-019090; to CX and L.S.).
000002682 520__ $$aThe 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.
000002682 536__ $$0G:(DE-Juel1)FUEK409$$2G:(DE-HGF)$$aFunktion und Dysfunktion des Nervensystems$$cP33$$x0
000002682 588__ $$aDataset connected to Web of Science, Pubmed
000002682 65320 $$2Author$$aPrions
000002682 65320 $$2Author$$aMonoclonal antibody
000002682 65320 $$2Author$$aConformation specificity
000002682 65320 $$2Author$$aComplementarity determining regions
000002682 65320 $$2Author$$aRecombinant antibodies
000002682 65320 $$2Author$$aRetro-inverso D-peptides
000002682 650_2 $$2MeSH$$aAmino Acid Sequence
000002682 650_2 $$2MeSH$$aAnimals
000002682 650_2 $$2MeSH$$aAntibody Affinity: immunology
000002682 650_2 $$2MeSH$$aCell Line
000002682 650_2 $$2MeSH$$aComplementarity Determining Regions: immunology
000002682 650_2 $$2MeSH$$aComplementarity Determining Regions: metabolism
000002682 650_2 $$2MeSH$$aMice
000002682 650_2 $$2MeSH$$aMice, Knockout
000002682 650_2 $$2MeSH$$aMolecular Sequence Data
000002682 650_2 $$2MeSH$$aPeptides: chemistry
000002682 650_2 $$2MeSH$$aPeptides: immunology
000002682 650_2 $$2MeSH$$aPeptides: metabolism
000002682 650_2 $$2MeSH$$aPrPC Proteins: immunology
000002682 650_2 $$2MeSH$$aPrPC Proteins: metabolism
000002682 650_2 $$2MeSH$$aPrPSc Proteins: immunology
000002682 650_2 $$2MeSH$$aPrPSc Proteins: metabolism
000002682 650_2 $$2MeSH$$aProtein Conformation
000002682 650_7 $$00$$2NLM Chemicals$$aComplementarity Determining Regions
000002682 650_7 $$00$$2NLM Chemicals$$aPeptides
000002682 650_7 $$00$$2NLM Chemicals$$aPrPC Proteins
000002682 650_7 $$00$$2NLM Chemicals$$aPrPSc Proteins
000002682 650_7 $$2WoSType$$aJ
000002682 7001_ $$0P:(DE-HGF)0$$aPetsch, B.$$b1
000002682 7001_ $$0P:(DE-Juel1)VDB72260$$aLeliveld, S. R.$$b2$$uFZJ
000002682 7001_ $$0P:(DE-HGF)0$$aMuyrers, J.$$b3
000002682 7001_ $$0P:(DE-HGF)0$$aSalwierz, A.$$b4
000002682 7001_ $$0P:(DE-HGF)0$$aMangels, Ch.$$b5
000002682 7001_ $$0P:(DE-HGF)0$$aSchwarzinger, St.$$b6
000002682 7001_ $$0P:(DE-HGF)0$$aRiesner, D.$$b7
000002682 7001_ $$0P:(DE-HGF)0$$aStitz, L.$$b8
000002682 7001_ $$0P:(DE-HGF)0$$aKorth, C.$$b9
000002682 773__ $$0PERI:(DE-600)2013448-4$$a10.1016/j.molimm.2008.07.023$$gVol. 46, p. 532 - 540$$p532 - 540$$q46<532 - 540$$tMolecular immunology$$v46$$x0161-5890$$y2009
000002682 8567_ $$uhttp://dx.doi.org/10.1016/j.molimm.2008.07.023
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