Molecular Design for Dual Modulation Effect of Amyloid Protein Aggregation

Lijuan Zhu, Yang Song, Pin Nan Cheng, Jeffrey S. Moore

Research output: Contribution to journalArticle

Abstract

Modulation of protein self-assembly has been a powerful strategy for controlling and understanding amyloid protein aggregation. Most modulators of amyloid aggregation only involve simple inhibition or acceleration. Here we report a new multivalent molecular motif, the polyethylenimine-perphenazine (PEI-P) conjugate which has a dual "acceleration-inhibition" modulation effect on amyloid β (Aβ) aggregation. Dose dependent results from Thioflavin T fluorescence assays, circular dichroism, and atomic force microscopy show that PEI-P conjugates accelerate formation of Aβ prefibrillar intermediates and then inhibit Aβ fibrillation. Furthermore, compared to perphenazine alone, PEI-P conjugates exhibit an enhanced inhibitory effect due to multivalency. Cell viability assays indicate that the PEI-P conjugates reduce the cytotoxicity of Aβ aggregates in a dose-dependent manner. This new modulation strategy may shed light on controlling amyloid aggregation, which offers a general concept for designing new modulators. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)8062-8068
Number of pages7
JournalJournal of the American Chemical Society
Volume137
Issue number25
DOIs
StatePublished - Jul 1 2015

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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