Inhibition of β-amyloid peptide self-assembly and cytotoxicity by poly(LVFF-co-β-amino ester).
The β-amyloid (Aβ) peptide plays an important role in the onset and progress of Alzheimer's disease (AD). Therefore, studies on inhibiting fibril formation and thus neurotoxicity of Aβ could be beneficial for the prevention and treatment of AD. We report a convenient synthetic approach for one-pot preparation of poly-(β-amino ester) copolymerized with the GGLVFF peptide, which is based on the frequently used inhibitor LVFF. The copolymer was found to efficiently inhibit the aggregation and fibrillation of Aβ42 by using fluorescence assay and atomic force microscopy. Reduced β-sheet formation of Aβ42 peptide after addition of copolymer was observed by circular dichroism. Furthermore, the cell viability assay confirmed that the toxicity of Aβ42 for SH-SY5Y cells was markedly reduced in the presence of copolymer. This could be beneficial for AD prevention and treatment and also for the molecular design of inhibitory agents for other amyloidoses.
National Center for Nanoscience and Technology, Beijing, 100190, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Hanyi
H
Xie
National Center for Nanoscience and Technology, Beijing, 100190, China.
Zengying
Z
Qiao
National Center for Nanoscience and Technology, Beijing, 100190, China.
Hao
H
Wang
National Center for Nanoscience and Technology, Beijing, 100190, China.|Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China.
Hongyang
H
Duan
National Center for Nanoscience and Technology, Beijing, 100190, China.
Yanlian
Y
Yang
National Center for Nanoscience and Technology, Beijing, 100190, China.
Chen
C
Wang
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000494:pharmacology*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017433:Protein Structure, Secondary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; C075222:amyloid beta-protein (1-42); C507253:poly(beta-amino ester)
aggregation; cytotoxicity; inhibitor; β-amyloid