We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of α-synuclein， amyloid β(1-42) (Aβ(1-42))， 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-Syn(36-46) peptide， which is a partial sequence of α-synuclein， prevented α-synuclein amyloid fibril formation but did not inhibit Aβ(1-42) fibril formation. In addition， the α-synuclein partial peptide modif... More
We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of α-synuclein， amyloid β(1-42) (Aβ(1-42))， 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-Syn(36-46) peptide， which is a partial sequence of α-synuclein， prevented α-synuclein amyloid fibril formation but did not inhibit Aβ(1-42) 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.
