Synthesis of d-amino acid peptides and their effect on beta-amyloid aggregation and toxicity in transgenic Caenorhabditis elegans

摘要: Genetic, biochemical, and pathological evidence supports that aggregation of amyloid-beta (Aβ) peptide into fibrillar structures rich in beta-sheets is implicated as the cause Alzheimer’s disease. Therefore, an attractive therapeutic strategy to prevent or alter aggregation. In this work we examine effects short d-peptides pgklvya, kklvffarrrra, kklvffa on Aβ vitro toxicity vivo. These peptides are based central hydrophobic region (residues 16–20), which believed be crucial self-association. The effect was examined by circular dichroism spectroscopy, Thioflavin T fluorescence, ANS binding assay. Transgenic Caenorhabditis elegans model used evaluate pharmacological Aβ-initiated toxicity. data suggested very effective at inhibiting fibrillogenesis Aβ. Among three tested, only pgklvya improved survival transgenic C. elegans. activity these correlates with their ability inhibit oligomerization. suggest should considered during future design peptide-based inhibitors amyloid deposition