Tripeptide Mimicing α-Mangostin to Inhibit the Aggregation of Amyloid-β by Breaking the Salt-bridge

OBJECTIVE to inhibit the Aβ aggregation and clarify the mechanism by the mimic peptide of α-mangostin which is discovered by binding on β-amyloid (Aβ) specifically. METHODS Phage-display was used to screen the peptides which binded on Aβ specificly against α-mangostin. The homologous sequence achieved by phage-display was analyzed to synthesise the tripeptides of DPN. The binding capability of DPN on Aβ was detected by surface plasmon resonance. The inhibition of DPN to Aβ aggregation by Thioflavin T. Molecular docking and site-specific mutagenesis on Aβ were used to clarify the mechanism. RESULTS The homologous sequence of DPN, where N was an acid or alkaline amino acid, was achieved by the experiment of phage-display. The pepetides with the sequence of DPN, were able to bind Aβ specifically. Especially, DPH would inhibit Aβ aggregation remarkably, which would be induced by the broken of salt-bridge between the residues of Asp23 (D₂₃) and Lys28 (K₂₈). CONCLUSION Pepetides with the sequence of DPN are able to bind Aβ specifically by mimicing α-mangostin. Especially, DPH would inhibit Aβ aggregation remarkably by breaking the salt-bridge between the residues of Asp23 (D₂₃) and Lys28 (K₂₈).