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Development of human antibody fragments directed towards synaptic acetylcholinesterase using a semi-synthetic phage display library

  • C. Flores-Flores
  • A. Nissim
  • S. Shochat
  • H. Soreq
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 62)

Abstract

Current Alzheimer’s disease therapies suppress acetylcholine hydrolysis by inhibiting acetylcholinesterase (AChE) at cholinergic synapses. However, anticholinesterases promote alternative splicing changing the composition of brain AChE variants. To study this phenomenon we developed monoclonal antibodies to acetylcholinesterase synaptic peptide (ASP), a synthetic peptide with the C-terminal sequence unique to the human synaptic variant AChE-S. Screening of a phage display human antibody library allowed the isolation of single-chain Fv (scFv) antibodies that were highly specific for ASP, and displayed closely related third complementarity determining regions of the variable heavy chain domain (VH-CDR3). BIAcore analysis demonstrated dissociation constants at the micromolar range: 1.6 × 10−6 and 2.0 × 10×6 M for ASP and the complete AChE-S protein, respectively. The anti-ASP antibodies provide a novel tool for studying the synaptic AChE-S variant, the expression of which is altered in ageing and dementia.

Keywords

Phage Display Antibody Fragment Phage Display Library scFv Antibody Phage Antibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2002

Authors and Affiliations

  • C. Flores-Flores
    • 1
  • A. Nissim
    • 2
    • 3
  • S. Shochat
    • 1
  • H. Soreq
    • 1
  1. 1.Department of Biological ChemistryThe Hebrew University of JerusalemJerusalemIsrael
  2. 2.Bone and Joint Research UnitSt. Bartholomew’s and Royal London School of Medicine and Dentistry, Queen MaryLondonUK
  3. 3.Felsenstein Medical Research Center, Sackler Faculty of MedicineTel Aviv University, Rabin Medical Center, Belinson CampusPetach TikvaIsrael

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