Structure-based design of conformation- and sequence-specific antibodies against amyloid β.

ABSTRACT: Conformation-specific antibodies that recognize aggregated proteins associated with several conformational disorders (e.g., Parkinson and prion diseases) are invaluable for diagnostic and therapeutic applications. However, no systematic strategy exists for generating conformation-specific antibodies that target linear sequence epitopes within misfolded proteins. Here we report a strategy for designing conformation- and sequence-specific antibodies against misfolded proteins that is inspired by the molecular interactions governing protein aggregation. We find that grafting small amyloidogenic peptides (6-10 residues) from the Aβ42 peptide associated with Alzheimer's disease into the complementarity determining regions of a domain (V(H)) antibody generates antibody variants that recognize Aβ

SUBMITTER: Perchiacca JM 

PROVIDER: S-EPMC3252897 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature