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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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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
(This article belongs to the Section Molecular Recognition)
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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 (CC BY 3.0).

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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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