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Name Ms. Khalilia Tillett
Organization or Institution University of South Florida
Presentation Type Poster
Topic Biochemistry / Chem Bio.
Title

N-Amino peptide inhibitors of Aβ1-42 aggregation

Author(s)

Khalilia C. Tillett and Juan R. Del Valle

Author Institution(s)

Department of Chemistry, University of South Florida, Tampa, FL
33620, USA

Abstract

The aggregation of amyloids into toxic oligomers is believed to be the key pathogenic event in the onset of Alzheimer’s Disease. Peptidomimetic modulators capable of destabilizing the propagation of an extended network of β-sheet fibrils are a well-established intervention strategy. Modifications to the amyloid beta (Aβ) peptides derived from the core domain, such as backbone N-methylation and macrocylization have afforded inhibitors capable of both antagonizing aggregation and reducing amyloid toxicity. Our lab has shown that peptide N-amination stabilizes the β-sheet conformation, however, this strategy has not been explored in the context of amyloid fibrillogenesis. Here we report the synthesis of N-aminated hexapeptides capable of inhibiting the fibrillization of full length Aβ42. A key feature of our design is N-amination at alternating positions of the core domain sequence. This allows for a hydrogen bonding edge capable of interacting with Aβ and a blocking edge capable of disrupting aggregation. Synthesis of the N-aminated analogs and initial biochemical evaluation will be presented.