Final Report Summary - FOLDHALO (Folding with Halogen Bonding)
Halogenation is a non-canonical protein post-translational modification that plays a pivotal role in various metabolic pathways and in host immune defense mechanism. On the other hand, halogenated proteins are a hallmark of certain human pathologies associated to oxidative stress. Halogenated tyrosines are, indeed, useful biomarkers of halogenative stress-induced diseases such as cystic fibrosis, atherosclerotic intima, sepsis, asthma, and Parkinson’s disease. The aim of the FoldHalo project was to try to demonstrate the potential that halogenation has to rewire amino acid and peptide self-assembly via inducing new supramolecular interactions. As model systems we focused on known amyloidogenic peptide sequences and demonstrated that halogenation, in general, promotes amyloidal fibrillation. Importantly, halogenation is a minimal structural modification, which, on the other hand, may induce a large difference in the peptide supramolecular behavior as a consequence of the rich variety of noncovalent interactions given by halogen atoms. Furthermore, halogen atoms in biological molecules are uncommon and, therefore, their site-specific incorporation into amino acids, oligopeptides, and proteins may confer a very high degree of control and specificity. In fact, we demonstrated that depending on the number, position, and nature of the introduced halogen atoms, halogenation promotes fibrillation and induce polymorphic transformations not seen in the wild-type peptides. This is general and applies to various peptides, either short or long sequences. Through this approach we obtained a series of new functional peptide materials, going from organocatalysts to superhydrogelators, nanostructures, nanocomposite, and bioelastomers. Finally, we exploited the acquired knowledge for engineering environmental antibodies capable of recognizing the thyroid hormone, thyroxine, and several halogenated endocrine disruptors with picomolar and nanomolar binding affinities, respectively.