Misfolding/aggregation of β-amyloid peptide lead to the formation of toxic oligomers or accumulation of amyloid plaques, which is a seminal step in the progression of Alzheimer's disease (AD). Despite continuous efforts in the development of therapeutic agents, the cure for AD remains a major challenge. Owing to specific binding affinity of structure-based peptides, we report the synthesis of new peptide-based inhibitors derived from the C-terminal sequences, Aβ and Aβ. Preliminary screening using MTT cell viability assay and corroborative results from ThT fluorescence assay revealed a tripeptide showing significantly effective inhibition towards Aβ aggregation and induced toxicity. Peptide 3 exhibited exce... More
Misfolding/aggregation of β-amyloid peptide lead to the formation of toxic oligomers or accumulation of amyloid plaques, which is a seminal step in the progression of Alzheimer's disease (AD). Despite continuous efforts in the development of therapeutic agents, the cure for AD remains a major challenge. Owing to specific binding affinity of structure-based peptides, we report the synthesis of new peptide-based inhibitors derived from the C-terminal sequences, Aβ and Aβ. Preliminary screening using MTT cell viability assay and corroborative results from ThT fluorescence assay revealed a tripeptide showing significantly effective inhibition towards Aβ aggregation and induced toxicity. Peptide 3 exhibited excellent cell viability of 94.3 % at 2 μM and of 100 % at 4 μM and 10 μM. CD study showed that peptide 3 restrict the conformation transition of Aβ peptide towards cross-β-sheet structure and electron microscopy validated the absence of Aβ aggregates as indicated by the altered morphology of Aβ in the presence of peptide 3. The HRMS-ESI, DLS and ANS studies were performed to gain mechanistic insights into the effect of inhibitor against Aβ aggregation. This Aβ-derived ultrashort motif provides impetus for the development of peptide-based anti-AD agents.
