B06 Kapurniotu: : Exploiting cross-amyloid interfaces to design peptides as modulators of amyloid self-assembly

Amyloid self-assembly is linked to devastating cell-/neurodegenerative diseases including Alzheimer’s disease (AD), type 2 diabetes (T2D), and Parkinson’s disease (PD). However, the design of effective amyloid inhibitors is a great challenge mostly due to the dynamic nature of most amyloidogenic proteins. "Cross-amyloid" interactions have emerged as key modulators of amyloid self-assembly. Our project aims to understand and exploit cross-amyloid interactions to design leads for anti-amyloid drugs. So far, we devised conformationally constrained peptides mimicking (cross-)amyloid interaction surfaces as potent amyloid inhibitors of Aβ (AD), IAPP (T2D), and insulin. Next steps comprise inhibitor optimisation, characterisation of structural and molecular determinants of their function, and application of our inhibitor design concepts to control cross-interactions of α-synuclein (PD) with IAPP and related amyloidogenic processes.