Polymer–Peptide Conjugates Disassemble Amyloid β Fibrils in a Molecular-Weight Dependent Manner

Song, Yang; Moore, Edwin G.; Guo, Yanshu; Moore, Jeffrey S.

doi:10.1021/jacs.7b00289

Title: Polymer–Peptide Conjugates Disassemble Amyloid β Fibrils in a Molecular-Weight Dependent Manner

Journal Article · Tue Mar 14 04:00:00 UTC 2017 · Journal of the American Chemical Society

DOI: https://doi.org/10.1021/jacs.7b00289 · OSTI ID:1425495

^[1]; Moore, Edwin G. ^[2]; Guo, Yanshu ^[3];

^[4]

Univ. of Illinois, Urbana, IL (United States). Dept. of Chemistry. Beckman Inst. for Advanced Science and Technology; University of Illinois at Urbana-Champaign
Univ. of Illinois, Urbana, IL (United States). Dept. of Chemistry
Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology
Univ. of Illinois, Urbana, IL (United States). Dept. of Chemistry. Beckman Inst. for Advanced Science and Technology

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, in this paper 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. Finally, the mPPCs may thus offer a general macromolecular design concept that breaks down existing amyloid fibrils in a predictable fashion.

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Research Organization:: Univ. of Illinois, Urbana, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: FG02-07ER46471

OSTI ID:: 1425495

Journal Information:: Journal of the American Chemical Society, Journal Name: Journal of the American Chemical Society Journal Issue: 12 Vol. 139; ISSN 0002-7863

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Heteromultivalent peptide recognition by co-assembly of cyclodextrin and calixarene amphiphiles enables inhibition of amyloid fibrillation Xu, Zhe; Jia, Shaorui; Wang, Wei Nature Chemistry, Vol. 11, Issue 1 https://doi.org/10.1038/s41557-018-0164-y	journal	November 2018
A cationic polymethacrylate-copolymer acts as an agonist for β-amyloid and an antagonist for amylin fibrillation Sahoo, Bikash R.; Genjo, Takuya; Nakayama, Takahiro W. Chemical Science, Vol. 10, Issue 14 https://doi.org/10.1039/c8sc05771k	journal	January 2019
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