Human single chain Fv antibodies and a complementarity determining region-derived peptide binding to amyloid-beta 1-42.
A library of phage-displayed human single-chain Fv (scFv) antibodies was selected against the human amyloid-beta peptide (Abeta42). Two new anti-Abeta42 phage-displayed scFvs antibodies were obtained, and the sequences of their V(H) and Vkappa 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 Abeta42 in ELISA. Furthermore, we showed for the first time that an HCDR3-based peptide had neuroprotective potential against Abeta42 neurotoxicity in rat cultured hippocampal neurons. Our results suggest that not only scFvs recognizing Abeta42 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.
Manoutcharian
K
K
Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), AP 70228, Cuidad Universitaria, Mexico DF, 04510, Mexico.
Acero
G
G
Munguia
M E
ME
Becerril
B
B
Massieu
L
L
Govezensky
T
T
Ortiz
E
E
Marks
J D
JD
Cao
C
C
Ugen
K
K
Gevorkian
G
G
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000032:analysis / Q000378:metabolism; D002478:Cells, Cultured; D022801:Complementarity Determining Regions / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000032:analysis / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D016229:Amyloid beta-Peptides; D000906:Antibodies; D022801:Complementarity Determining Regions; D007135:Immunoglobulin Variable Region; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)