Human single chain Fv antibodies and a complementarity determining region-derived peptide binding to amyloid-beta 1-42
Por:
Manoutcharian K., Acero G., Munguia M.E., Becerril B., Massieu L., Govezensky T., Ortiz E., Marks J.D., Cao C., Ugen K., Gevorkian G.
Publicada:
1 ene 2004
Resumen:
A library of phage-displayed human single-chain Fv (scFv) antibodies was selected against the human amyloid-beta peptide (A?42). Two new anti-A?42 phage-displayed scFvs antibodies were obtained, and the sequences of their VH and V? genes were analyzed. A synthetic peptide based on the sequence of Ig heavy chain (VH) complementarity- determining region (HCDR3) of the clone with the highest recognition signal was generated and determined to bind to A?42 in ELISA. Furthermore, we showed for the first time that an HCDR3-based peptide had neuroprotective potential against A?42 neurotoxicity in rat cultured hippocampal neurons. Our results suggest that not only scFvs recognizing A?42 but also synthetic peptides based on the VH CDR3 sequences of these antibodies may be novel potential candidates for small molecule-based Alzheimer's disease (AD) therapy. © 2004 Elsevier Inc. All rights reserved.
Filiaciones:
Manoutcharian K.:
Inst. de Invest. Biomédicas, Univ. Nac. Auton. de Mex., AP 70228, Cuidad Univ., 04510, Mexico DF, Mexico
Acero G.:
Inst. de Invest. Biomédicas, Univ. Nac. Auton. de Mex., AP 70228, Cuidad Univ., 04510, Mexico DF, Mexico
Munguia M.E.:
Inst. de Invest. Biomédicas, Univ. Nac. Auton. de Mex., AP 70228, Cuidad Univ., 04510, Mexico DF, Mexico
Becerril B.:
Instituto de Biotecnologia, UNAM, Mexico
Massieu L.:
Inst. de Fisiología Celular, UNAM, Mexico
Govezensky T.:
Inst. de Invest. Biomédicas, Univ. Nac. Auton. de Mex., AP 70228, Cuidad Univ., 04510, Mexico DF, Mexico
Ortiz E.:
Instituto de Biotecnologia, UNAM, Mexico
Marks J.D.:
Dept. Anesthesia Pharmaceutical C., Univ. California S. Francisco G., San Francisco, CA, United States
Cao C.:
Dept. Med. Microbiol. and Immunol., Univ. of S. Florida Coll. of Med., Tampa, FL, United States
Ugen K.:
Dept. Med. Microbiol. and Immunol., Univ. of S. Florida Coll. of Med., Tampa, FL, United States
Gevorkian G.:
Inst. de Invest. Biomédicas, Univ. Nac. Auton. de Mex., AP 70228, Cuidad Univ., 04510, Mexico DF, Mexico
Department of Immunology, Inst. de Invest. Biomédicas, Univ. Nac. Auton. Mex. , Apdo. P., Mexico DF, Mexico
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