Human single chain Fv antibodies and a complementarity determining region-derived peptide binding to amyloid-beta 1–42

Abstract

A library of phage-displayed human single-chain Fv (scFv) antibodies was selected against the human amyloid-beta peptide (Aβ42). Two new anti-Aβ42 phage-displayed scFvs antibodies were obtained, and the sequences of their V H and Vκ genes were analyzed. A synthetic peptide based on the sequence of Ig heavy chain (V H) complementarity-determining region (HCDR3) of the clone with the highest recognition signal was generated and determined to bind to Aβ42 in ELISA. Furthermore, we showed for the first time that an HCDR3-based peptide had neuroprotective potential against Aβ42 neurotoxicity in rat cultured hippocampal neurons. Our results suggest that not only scFvs recognizing Aβ42 but also synthetic peptides based on the V H CDR3 sequences of these antibodies may be novel potential candidates for small molecule-based Alzheimer's disease (AD) therapy.