Enhanced self-assembly of the 7-12 sequence of amyloid-? peptide by tyrosine bromination

Alzheimer's disease (AD) is a serious neuropathology related to the misfolded assembly state of amyloid-beta (A?40 and A?42) peptides. It has been demonstrated that protein post-translation modifications (PPTMs) of the more hydrophilic N-term moiety of the A? peptide affect its aggregation kinetics and interaction with the environment. Considering that chlorination and bromination are non-canonical PPTMs found in various metabolic pathways and often correlated to inflammatory responses, halogenation of the Y10 of the A? N-term could be a putative in vivo modification with implications in the A? peptide aggregation propensity. In this framework, we chose as a model system, a short peptide sequence, DSGYEV (i.e. residues 7-12 of the A? N-term) and studied its self-assembly behaviour in comparison to its chlorinated and brominated derivatives. Our results show that Y10 halogenation works as a molecular trigger of the peptide self-assembly in solution, promoting the formation of more structured aggregates.