Project Details
Exploiting cross-amyloid interfaces to design peptides as modulators of amyloid self-assembly (B06)
Subject Area
Biochemistry
Term
from 2012 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 201302640
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.
DFG Programme
Collaborative Research Centres
Applicant Institution
Technische Universität München (TUM)
Project Head
Professorin Dr. Aphrodite Kapurniotu