Partial peptide of ?-synuclein modified with small-molecule inhibitors specifically inhibits amyloid fibrillation of ?-synuclein.

ABSTRACT: We have previously reported that pyrroloquinoline quinone (PQQ) prevents the amyloid formation of ?-synuclein, amyloid ?(1-42) (A?(1-42)), and mouse prion protein. Moreover, PQQ-modified ?-synuclein and a proteolytic fragment of the PQQ-modified ?-synuclein are able to inhibit the amyloid formation of ?-synuclein. Here, we identified the peptide sequences that play an important role as PQQ-modified specific peptide inhibitors of ?-synuclein. We demonstrate that the PQQ-modified ?-Syn(36-46) peptide, which is a partial sequence of ?-synuclein, prevented ?-synuclein amyloid fibril formation but did not inhibit A?(1-42) fibril formation. In addition, the ?-synuclein partial peptide modified with other small-molecule inhibitors, Baicalein and epigallocatechin gallate (EGCG), prevented ?-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.

SUBMITTER: Yoshida W 

PROVIDER: S-EPMC3588004 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature