Synthesis and mechanistic study of ultrashort peptides that inhibits Alzheimer’s Aβ-aggregation-induced neurotoxicity
Thioflavin
Viability assay
Tripeptide
Amyloid (mycology)
Neurotoxicity
MTT assay
DOI:
10.1016/j.bioorg.2024.107159
Publication Date:
2024-01-29T16:27:01Z
AUTHORS (6)
ABSTRACT
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, Aβ38-40 and Aβ40-42. Preliminary screening using MTT cell viability assay and corroborative results from ThT fluorescence assay revealed a tripeptide showing significantly effective inhibition towards Aβ1-42 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 Aβ1-42 peptide towards cross-β-sheet structure and electron microscopy validated the absence of Aβ aggregates as indicated by the altered morphology of Aβ1-42 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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (26)
CITATIONS (8)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....