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Int. J. Mol. Sci. 2013, 14(2), 2590-2600; doi:10.3390/ijms14022590
Article

Partial Peptide of α-Synuclein Modified with Small-Molecule Inhibitors Specifically Inhibits Amyloid Fibrillation of α-Synuclein

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,
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 and *
Department of Biotechnology, Graduate School of Engineering, Tokyo University of Agriculture & Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan
* Author to whom correspondence should be addressed.
Received: 5 October 2012 / Revised: 29 December 2012 / Accepted: 18 January 2013 / Published: 28 January 2013
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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.
Keywords: α-synuclein; amyloid β; pyrroloquinoline quinone; Baicalein; EGCG α-synuclein; amyloid β; pyrroloquinoline quinone; Baicalein; EGCG
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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