Methodology in SPPS to afford stapled peptides inspired by the EF helix of TTR

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that causes progressive cognitive and functional decline in patients. Affecting more than 35 million people, AD is currently the most common form of senile dementia. The disease is characterised by the formation of extracellular β-amyloid (Aβ1-40 and Aβ1-42) deposits and intracellular hyperphosphorylated tau, which are thought to be the major contributors to tissue damage. The incomplete understanding of the aetiopathogenesis of Alzheimer's disease has so far prevented the development of treatments capable of halting the progression of the disease. Recently, several studies have shown that transthyretin (TTR), a human homotetrameric protein, can bind Aβ and exert a neuroprotective function. In this context, the research project focused on the synthesis and characterisation of stapled peptide probes designed to mimic the helical conformation of TTR involved in protein-protein interactions between TTR and Aβ. These probes will serve as exploratory tools to better understand the positive cross-interaction between two amyloidogenic proteins, with the aim of developing future therapeutic approaches to treat the pathological amyloid aggregation in Alzheimer's disease.