(1) Fourth (PPI-G4-Mal) and fifth (PPI-G5-Mal) generation PPI glycodendrimers have the capacity to interfere with the Alzheimer’s amyloid peptide Aβ(1–40) fibril formation process.
(2) The interaction is generation-dependent: PPI-G5-Mal is highly effective at blocking amyloid fibril formation generating granular nonfibrillar amorphous aggregates, whereas PPI-G4-Mal generates clumped fibrils at low dendrimer–peptide ratios and amorphous aggregates at high ratios.
(3) PPI-G4-Mal and PPI-G5-Mal are nontoxic to PC12 and SH-SY5Y cells.
(4) Glycodendrimer–peptide amorphous aggregates are shown to be toxic to PC12 cells.
Their fibril clumping capacity makes glycodendrimers potential effective anti-amyloidogenic agents.
