Synthetic dimeric A?(28-40) mimics the complex epitope of human anti-A? autoantibodies against toxic A? oligomers.

ABSTRACT: Covalently linked carboxyl-terminal segments of the ?-amyloid peptide (A?) were tested for their qualification as minimal conformational epitopes of the naturally occurring human autoantibodies against ?-amyloid (nAbs-A?). nAbs-A? specifically recognize the toxic oligomers of A? and not the monomeric or the fibrillar forms of A?. The synthetic dimers of A?(28-40) described herein mimic the toxic A? oligomers but are not kinetic intermediates with uncertain compositions. CD spectra identified a surprisingly rich conformational behavior of selected miniamyloids. We observed a highly cooperative conformational transition of ?-sheet to ?-helix upon the addition of the helix enforcing co-solvent hexafluoroisopropanol. The CD curves of dimer 9 resembled, in a completely reversible manner, the CD spectra measured during the irreversible fibrillation of the parent A?(1-40). Synthetic peptide epitopes with high affinities for nAbs-A? are needed to identify the physiological roles of nAbs-A? and are promising epitopes for vaccination experiments.

SUBMITTER: Roeder AM 

PROVIDER: S-EPMC3779759 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature