Aphrodite Kapurniotu
Professor
Technical University of Munich
Talk Information
Peptide Therapeutics from Discovery to the Clinic
17 June 2025, 11:05am - 11:20am, in the Pacific Jewel Ballroom
L30 – Designed Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Sseeded Amyloid Self-Assembly of Alpha-Synuclein
Professor Aphrodite Kapurniotu is a distinguished chemist specializing in peptide biochemistry. She currently holds the Professorship for Peptide Biochemistry at the Technical University of Munich, TUM, where she leads the Division of Peptide Biochemistry within the TUM School of Life Sciences.
Academic Background
Professor Kapurniotu studied chemistry in Athens and earned her Ph.D. in Tübingen in 1990. She conducted postdoctoral research at Rutgers University and the Picower Institute for Medical Research in the United States from 1992 to 1995. After completing her Habilitation in Biochemistry at the University of Tübingen in 2001, she led a biomedical research group at RWTH Aachen. In 2007, she was appointed Professor for Peptide Biochemistry at TUM.
Research Focus
Professor Kapurniotu's research centers on developing peptide-based molecules as therapeutic leads and tools to understand the molecular mechanisms of amyloid diseases, particularly Alzheimer's disease and type 2 diabetes. Additionally, her work involves characterizing interactions of inflammatory chemokines in atherosclerosis and developing peptide-based inhibitors.
Notable Contributions
Her innovative research has significantly advanced the understanding of peptide-based therapeutics and their applications in combating amyloid-related diseases. Her contributions have been instrumental in developing novel strategies to interfere with protein misfolding and aggregation processes.
Professional Engagements
Beyond her research, Professor Kapurniotu serves as the Gender Equality Officer of the TUM School of Life Sciences and has been a member of the School Council since 2009. In this role, she actively contributes to promoting gender equality and supporting the academic community within the university.
Through her pioneering research and commitment to academic leadership, Professor Aphrodite Kapurniotu continues to make significant contributions to the field of peptide science and the broader scientific community.
Macrocyclic Peptides as Multi-Targeting Inhibitors of Amyloid Self-Assembly in Neurodegenerative and Metabolic Diseases
Department of Chemistry, Technical University of Munich, Germany
Protein aggregation into cytotoxic oligomers and amyloid fibrils is linked to numerous devastating cell- or neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), and type 2 diabetes (T2D). The key amyloid polypeptide in AD is the 40(42)-residue amyloid-β peptide (Aβ), in PD the 140-residue α-synuclein (αSyn), and in T2D the 37-residue islet amyloid polypeptide (IAPP) (or amylin).
T2D is regarded as a major risk factor for PD. Cross-interactions between αSyn and IAPP might be a molecular link between T2D and PD. In fact, IAPP fibrils can act as “cross-seeds,” thus accelerating amyloid self-assembly of αSyn, and IAPP and αSyn have been reported to co-localize in PD brains. Therefore, designing inhibitors of both self- and IAPP-cross-seeded αSyn amyloid self-assembly could be a useful approach to intervene with PD pathogenesis.
However, αSyn and IAPP are intrinsically disordered and their cross-interaction sites have been unknown, which hinders inhibitor design. Here we present our studies on macrocyclic peptides designed to mimic putative IAPP self-/cross-interaction sites. These peptides were found to be nanomolar inhibitors of both self- and IAPP-cross-seeded amyloid self-assembly of αSyn1. In addition, these peptides block Aβ-mediated cross-seeding of αSyn and inhibit amyloid self-assembly of IAPP and/or Aβ1,2.
Based on their broad-spectrum anti-amyloid function and additional drug-like features, these multi-targeting macrocyclic peptides are promising leads for multifunctional anti-amyloid drugs in PD, T2D, AD, and their comorbidities.
1. Hornung et al. Angew. Chem. Int. Ed. 2025 (in press).
2. Spanopoulou et al. Angew. Chem. Int. Ed. 2018, 57, 14503–14508.