Molecular Design for Dual Modulation Effect of Amyloid Protein Aggregation

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