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@ARTICLE{MllerSchiffmann:2682,
      author       = {Müller-Schiffmann, A. and Petsch, B. and Leliveld, S. R.
                      and Muyrers, J. and Salwierz, A. and Mangels, Ch. and
                      Schwarzinger, St. and Riesner, D. and Stitz, L. and Korth,
                      C.},
      title        = {{C}omplementarity determining regions of an anti-prion
                      protein sc{F}v fragment orchestrate conformation specificity
                      and antiprion activity},
      journal      = {Molecular immunology},
      volume       = {46},
      issn         = {0161-5890},
      address      = {Oxford},
      publisher    = {Pergamon Press},
      reportid     = {PreJuSER-2682},
      pages        = {532 - 540},
      year         = {2009},
      note         = {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.).},
      abstract     = {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.},
      keywords     = {Amino Acid Sequence / Animals / Antibody Affinity:
                      immunology / Cell Line / Complementarity Determining
                      Regions: immunology / Complementarity Determining Regions:
                      metabolism / Mice / Mice, Knockout / Molecular Sequence Data
                      / Peptides: chemistry / Peptides: immunology / Peptides:
                      metabolism / PrPC Proteins: immunology / PrPC Proteins:
                      metabolism / PrPSc Proteins: immunology / PrPSc Proteins:
                      metabolism / Protein Conformation / Complementarity
                      Determining Regions (NLM Chemicals) / Peptides (NLM
                      Chemicals) / PrPC Proteins (NLM Chemicals) / PrPSc Proteins
                      (NLM Chemicals) / J (WoSType)},
      cin          = {INB-2},
      ddc          = {570},
      cid          = {I:(DE-Juel1)VDB805},
      pnm          = {Funktion und Dysfunktion des Nervensystems},
      pid          = {G:(DE-Juel1)FUEK409},
      shelfmark    = {Biochemistry $\&$ Molecular Biology / Immunology},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:18973947},
      UT           = {WOS:000263429500004},
      doi          = {10.1016/j.molimm.2008.07.023},
      url          = {https://juser.fz-juelich.de/record/2682},
}