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

  • Conference paper
Ageing and Dementia Current and Future Concepts

Part of the book series: Journal of Neural Transmission. Supplementa ((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.

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Author information

Authors and Affiliations

  1. Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

    C. Flores-Flores, S. Shochat & Dr. H. Soreq

  2. Bone and Joint Research Unit, St. Bartholomew’s and Royal London School of Medicine and Dentistry, Queen Mary, London, UK

    A. Nissim

  3. Felsenstein Medical Research Center, Sackler Faculty of Medicine, Tel Aviv University, Rabin Medical Center, Belinson Campus, Petach Tikva, Israel

    A. Nissim

Authors
  1. C. Flores-Flores
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  2. A. Nissim
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  3. S. Shochat
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  4. Dr. H. Soreq
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Editor information

Editors and Affiliations

  1. Institut für Klinische Neurobiologie, Kenyongasse 18/7, A-1070, Wien, Austria

    Kurt A. Jellinger

  2. Universitätsklinik für Neurologie, Auenbruggerplatz 22, A-8036, Graz, Austria

    Reinhold Schmidt

  3. JWS Research Forschungslabor GmbH, Rankengasse 28, A-8020, Graz, Austria

    Manfred Windisch

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© 2002 Springer-Verlag Wien

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Flores-Flores, C., Nissim, A., Shochat, S., Soreq, H. (2002). Development of human antibody fragments directed towards synaptic acetylcholinesterase using a semi-synthetic phage display library. In: Jellinger, K.A., Schmidt, R., Windisch, M. (eds) Ageing and Dementia Current and Future Concepts. Journal of Neural Transmission. Supplementa, vol 62. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6139-5_16

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  • DOI: https://doi.org/10.1007/978-3-7091-6139-5_16

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83796-2

  • Online ISBN: 978-3-7091-6139-5

  • eBook Packages: Springer Book Archive

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