Combinatorial development of chemical receptors for c-terminal oligopeptides using an Alzheimer model peptide
Project management at the University of Würzburg:
The self-aggregation of small peptides is responsible both in animals and humans for a variety of neuro degenerative diseases such as Scrapie, BSE, Creutzfeldt-Jakob or Alzheimer disease (AD). For example, the senile plaques found within the brain of AD patients consist of an insoluble aggregate of a 39 ? 42 residue peptide, called amyloid b-peptide (Ab). Though the exact correlation between plaque formation and the onset of the disease is not quite clear yet, prevention of Ab self-aggregation might be a strategy to delay the onset of neuronal degeneration. Recent work has focused on small model peptides representing the self-recognition sequences of Ab to identify the structural and thermodynamic parameters that control its self-association and hence also possible interactions with aggregation inhibitors.
In this context, we use the solid phase synthesis of combinatorial libraries of possible receptor structures, which are screened in an on bead fluorescence assay for their binding to the tetrapeptide Val-Val-Ile-Ala, representing the C-terminal end (39-42) of Ab.
Projekt period: from 10.2000 to 09.2002
DFG ,Granting date: 10.07.2000