title: Polymer-Peptide Conjugates Disassemble Amyloid β Fibrils in a Molecular-Weight Dependent Manner.
abstract: Amyloid aggregation and deposition are associated with many intractable human diseases. Although the inhibition of amyloid protein aggregation has been well-studied, the disaggregation and dissolution of existing amyloid fibrils is less known. Taking a fibrillar assembly of amyloid β (Aβ) peptide as the model system, here we report multivalent polymer-peptide conjugates (mPPCs) that disassemble preformed Aβ fibrils into dispersible sub-100 nm structures. Atomic force microscopy and dynamic light scattering studies show that the disassembly rate of preformed Aβ fibrils is controlled by the molecular weight of mPPCs. Rate equations on fibril disappearance are deduced from a simple model, which indicate that the disassembly reaction is first-order in the concentration of Aβ fibrils and a pseudo-first-order reaction in the concentration of peptide moieties on mPPCs, respectively. We eliminate the possibility that the disassembly occurs by the association between mPPCs and Aβ monomer/oligomers based on circular dichroism and Thioflavin T fluorescence assays. It is mostly likely that the mPPCs disassemble Aβ fibrils through a direct interaction. The mPPCs may thus offer a general macromolecular design concept that breaks down existing amyloid fibrils in a predictable fashion.
authors.affiliation: Department of Chemistry and ‡ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Yang
authors.identifier: 0000-0002-9279-3284
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Chemistry and ‡ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Moore
authors.affiliation: Department of Chemistry and ‡ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Yanshu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Chemistry and ‡ Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
authors.forename: Jeffrey S
authors.identifier: 0000-0001-5841-6269
authors.initials: JS
authors.lastname: Moore
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D008968:Molecular Conformation; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D011108:Polymers