Abstract: We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of α-synuclein, amyloid β1–42 (Aβ1–42), and mouse prion protein. Moreover, PQQ-modified α-synuclein and a proteolytic fragment of the PQQ-modified α-synuclein are able to inhibit the amyloid formation of α-synuclein. Here, we identified the peptide sequences that play an important role as PQQ-modified specific peptide inhibitors of α-synuclein. We demonstrate that the PQQ-modified α-Syn36–46 peptide, which is a partial sequence of α-synuclein, prevented α-synuclein amyloid fibril formation but did not inhibit Aβ1–42 fibril formation. In addition, the α-synuclein partial peptide modified with other small-molecule inhibitors, Baicalein and epigallocatechin gallate (EGCG), prevented α-synuclein fibril formation. Currently reported quinone amyloid inhibitors do not have selectivity toward protein molecules. Therefore, our achievements provide a novel strategy for the development of targeted specific amyloid formation inhibitors: the combination of quinone compounds with specific peptide sequence from target proteins involved in amyloid formation.
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Yoshida, W.; Kobayashi, N.; Sasaki, Y.; Ikebukuro, K.; Sode, K. Partial Peptide of α-Synuclein Modified with Small-Molecule Inhibitors Specifically Inhibits Amyloid Fibrillation of α-Synuclein. Int. J. Mol. Sci. 2013, 14, 2590-2600.
Yoshida W, Kobayashi N, Sasaki Y, Ikebukuro K, Sode K. Partial Peptide of α-Synuclein Modified with Small-Molecule Inhibitors Specifically Inhibits Amyloid Fibrillation of α-Synuclein. International Journal of Molecular Sciences. 2013; 14(2):2590-2600.
Yoshida, Wataru; Kobayashi, Natsuki; Sasaki, Yasuhiko; Ikebukuro, Kazunori; Sode, Koji. 2013. "Partial Peptide of α-Synuclein Modified with Small-Molecule Inhibitors Specifically Inhibits Amyloid Fibrillation of α-Synuclein." Int. J. Mol. Sci. 14, no. 2: 2590-2600.