EventCemile Elif Özçelik
Peptide drug discovery for pathogenic amyloids
Amyloid fibrils are very stable, ordered cross-Î² structured, resistant to protease degradation, proteinaceous composits. All amyloids have different peptide/protein sequences although they express similar structural properties. Most of amyloids are associated with various severe diseases such as neurodegenerative diseases. Up to now, there were several therapeutic approaches that are only effective in symptoms of disease conditions by masking or slowing down the symptom developments. Nonetheless, different approaches are developed for inhibiting amyloid aggregation. Inhibition of monomeric amyloid units, which are developed into amyloid aggregates, can be promising novel approach for halting disease-condition developments. In this thesis, candidate ligand peptides that cease aggregation of huntingtin, Î±-synuclein and amyloid-Î² were selected by using different types of display systems, which are bacterial surface display, yeast surface display and phage display technologies. The monomeric amyloid units of these proteins were expressed on surfaces of bacterial cells and yeast cells in order to expressing monomeric units with a proper folding and avoiding aggregation after expression without interacting with each other. Candidate ligand peptides were selected against neurodegenerative amyloids by M13 phage display library. 12 amino acid-long peptides displayed on the minor coat protein pIII of M13 bacteriophage were selected against neurodegenerative amyloids for inhibiting protein aggregation purpose in the very first step of aggregation pathway.