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 00:00:00 EDT 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];

^[1]

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

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

Grant/Contract Number:: FG02-07ER46471

OSTI ID:: 1425495

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

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 49 works

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References (27)

The Amyloid State of Proteins in Human Diseases Eisenberg, David; Jucker, Mathias Cell, Vol. 148, Issue 6 https://doi.org/10.1016/j.cell.2012.02.022	journal	March 2012
Protein aggregation diseases: pathogenicity and therapeutic perspectives Aguzzi, Adriano; O'Connor, Tracy Nature Reviews Drug Discovery, Vol. 9, Issue 3 https://doi.org/10.1038/nrd3050	journal	March 2010
Protein Misfolding, Functional Amyloid, and Human Disease Chiti, Fabrizio; Dobson, Christopher M. Annual Review of Biochemistry, Vol. 75, Issue 1 https://doi.org/10.1146/annurev.biochem.75.101304.123901	journal	June 2006
Inhibition of Amyloid Formation Härd, Torleif; Lendel, Christofer Journal of Molecular Biology, Vol. 421, Issue 4-5 https://doi.org/10.1016/j.jmb.2011.12.062	journal	August 2012
Molecular Design for Dual Modulation Effect of Amyloid Protein Aggregation Zhu, Lijuan; Song, Yang; Cheng, Pin-Nan Journal of the American Chemical Society, Vol. 137, Issue 25 https://doi.org/10.1021/jacs.5b01651	journal	June 2015
Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease Bard, Frédérique; Cannon, Catherine; Barbour, Robin Nature Medicine, Vol. 6, Issue 8 https://doi.org/10.1038/78682	journal	August 2000
Small-Molecule Inhibitors of Islet Amyloid Polypeptide Fibril Formation Mishra, Rajesh; Bulic, Bruno; Sellin, Daniel Angewandte Chemie International Edition, Vol. 47, Issue 25 https://doi.org/10.1002/anie.200705372	journal	June 2008
EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity Bieschke, Jan; Russ, Jenny; Friedrich, Ralf P. Proceedings of the National Academy of Sciences, Vol. 107, Issue 17 https://doi.org/10.1073/pnas.0910723107	journal	April 2010
Structure-based design of non-natural amino-acid inhibitors of amyloid fibril formation Sievers, Stuart A.; Karanicolas, John; Chang, Howard W. Nature, Vol. 475, Issue 7354 https://doi.org/10.1038/nature10154	journal	June 2011
Efficient reversal of Alzheimer's disease fibril formation and elimination of neurotoxicity by a small molecule Blanchard, B. J.; Chen, A.; Rozeboom, L. M. Proceedings of the National Academy of Sciences, Vol. 101, Issue 40 https://doi.org/10.1073/pnas.0405941101	journal	September 2004
The Flavanol (−)-Epigallocatechin 3-Gallate Inhibits Amyloid Formation by Islet Amyloid Polypeptide, Disaggregates Amyloid Fibrils, and Protects Cultured Cells against IAPP-Induced Toxicity Meng, Fanling; Abedini, Andisheh; Plesner, Annette Biochemistry, Vol. 49, Issue 37 https://doi.org/10.1021/bi100939a	journal	September 2010
Tanshinones Inhibit Amyloid Aggregation by Amyloid-β Peptide, Disaggregate Amyloid Fibrils, and Protect Cultured Cells Wang, Qiuming; Yu, Xiang; Patal, Kunal ACS Chemical Neuroscience, Vol. 4, Issue 6 https://doi.org/10.1021/cn400051e	journal	March 2013
Inhibition of β-Amyloid(40) Fibrillogenesis and Disassembly of β-Amyloid(40) Fibrils by Short β-Amyloid Congeners Containing N -Methyl Amino Acids at Alternate Residues ^† Gordon, David J.; Sciarretta, Kimberly L.; Meredith, Stephen C. Biochemistry, Vol. 40, Issue 28 https://doi.org/10.1021/bi002416v	journal	July 2001
The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization Hamley, I. W. Chemical Reviews, Vol. 112, Issue 10 https://doi.org/10.1021/cr3000994	journal	June 2012
Amyloid β-sheet mimics that antagonize protein aggregation and reduce amyloid toxicity Cheng, Pin-Nan; Liu, Cong; Zhao, Minglei Nature Chemistry, Vol. 4, Issue 11 https://doi.org/10.1038/nchem.1433	journal	September 2012
Branched KLVFF Tetramers Strongly Potentiate Inhibition of β-Amyloid Aggregation Chafekar, Sidhartha M.; Malda, Hinke; Merkx, Maarten ChemBioChem, Vol. 8, Issue 15 https://doi.org/10.1002/cbic.200700338	journal	October 2007
Heterodivalent Linked Macrocyclic β-Sheets with Enhanced Activity against Aβ Aggregation: Two Sites Are Better Than One Cheng, Pin-Nan; Spencer, Ryan; Woods, R. Jeremy Journal of the American Chemical Society, Vol. 134, Issue 34 https://doi.org/10.1021/ja305416a	journal	August 2012
Multivalent Macromolecules Redirect Nucleation-Dependent Fibrillar Assembly into Discrete Nanostructures Song, Yang; Cheng, Pin-Nan; Zhu, Lijuan Journal of the American Chemical Society, Vol. 136, Issue 14 https://doi.org/10.1021/ja501102f	journal	February 2014
β-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: Implications for Alzheimer's therapy Soto, Claudio; Sigurdsson, Einar M.; Morelli, Laura Nature Medicine, Vol. 4, Issue 7 https://doi.org/10.1038/nm0798-822	journal	July 1998
Inhibition of Alzheimer's Amyloidosis by Peptides That Prevent β-Sheet Conformation Soto, Claudio; Kindy, Mark S.; Baumann, Marc Biochemical and Biophysical Research Communications, Vol. 226, Issue 3 https://doi.org/10.1006/bbrc.1996.1413	journal	September 1996
Inhibition of Aggregation of Amyloid Peptides by Beta-Sheet Breaker Peptides and Their Binding Affinity Viet, Man Hoang; Ngo, Son Tung; Lam, Nguyen Sy The Journal of Physical Chemistry B, Vol. 115, Issue 22 https://doi.org/10.1021/jp1116728	journal	June 2011
Alzheimer's Aβ42 and Aβ40 peptides form interlaced amyloid fibrils Gu, Lei; Guo, Zhefeng Journal of Neurochemistry, Vol. 126, Issue 3 https://doi.org/10.1111/jnc.12202	journal	March 2013
Mutations that Reduce Aggregation of the Alzheimer's Aβ42 Peptide: an Unbiased Search for the Sequence Determinants of Aβ Amyloidogenesis Wurth, Christine; Guimard, Nathalie K.; Hecht, Michael H. Journal of Molecular Biology, Vol. 319, Issue 5 https://doi.org/10.1016/S0022-2836(02)00399-6	journal	June 2002
Molecular recycling within amyloid fibrils Carulla, Natàlia; Caddy, Gemma L.; Hall, Damien R. Nature, Vol. 436, Issue 7050 https://doi.org/10.1038/nature03986	journal	July 2005
Thermodynamics of Aβ(1−40) Amyloid Fibril Elongation ^† O'Nuallain, Brian; Shivaprasad, Shankaramma; Kheterpal, Indu Biochemistry, Vol. 44, Issue 38 https://doi.org/10.1021/bi050927h	journal	September 2005
Inhibitors of Amyloid Toxicity Based on β-sheet Packing of Aβ40 and Aβ42 Sato, Takeshi; Kienlen-Campard, Pascal; Ahmed, Mahiuddin Biochemistry, Vol. 45, Issue 17 https://doi.org/10.1021/bi052485f	journal	April 2006
Steady-state and time-resolved Thioflavin-T fluorescence can report on morphological differences in amyloid fibrils formed by Aβ(1-40) and Aβ(1-42) Lindberg, David J.; Wranne, Moa S.; Gilbert Gatty, Mélina Biochemical and Biophysical Research Communications, Vol. 458, Issue 2 https://doi.org/10.1016/j.bbrc.2015.01.132	journal	March 2015

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Metal–Organic Frameworks Harness Cu Chelating and Photooxidation Against Amyloid β Aggregation in Vivo Yu, Dongqin; Guan, Yijia; Bai, Fuquan Chemistry – A European Journal, Vol. 25, Issue 14 https://doi.org/10.1002/chem.201805835	journal	February 2019
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
Engineering Versatile Nanoparticles for Near‐Infrared Light‐Tunable Drug Release and Photothermal Degradation of Amyloid β Lai, Yi; Zhu, Yingying; Xu, Zhiai Advanced Functional Materials, Vol. 30, Issue 11 https://doi.org/10.1002/adfm.201908473	journal	January 2020
One-Pot Synthesis of Thermoresponsive Amyloidogenic Peptide-Polymer Conjugates via Thio-Bromo “Click” Reaction of RAFT Polymers Kumar, Sonu; Deike, Stefanie; Binder, Wolfgang H. Macromolecular Rapid Communications, Vol. 39, Issue 2 https://doi.org/10.1002/marc.201700507	journal	October 2017
Supramolecular assembly of functional peptide–polymer conjugates Otter, Ronja; Besenius, Pol Organic & Biomolecular Chemistry, Vol. 17, Issue 28 https://doi.org/10.1039/c9ob01191a	journal	January 2019
Selection of Secondary Structures of Heterotypic Supramolecular Peptide Assemblies by an Enzymatic Reaction Li, Jie; Zhan, Ziqing; Du, Xuewen Angewandte Chemie International Edition, Vol. 57, Issue 36 https://doi.org/10.1002/anie.201806992	journal	September 2018
Synthesis and Aggregation of Polymer‐Amyloid β Conjugates Evgrafova, Zhanna; Rothemund, Sven; Voigt, Bruno Macromolecular Rapid Communications, Vol. 41, Issue 1 https://doi.org/10.1002/marc.201900378	journal	October 2019
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
Selection of Secondary Structures of Heterotypic Supramolecular Peptide Assemblies by an Enzymatic Reaction Li, Jie; Zhan, Ziqing; Du, Xuewen Angewandte Chemie, Vol. 130, Issue 36 https://doi.org/10.1002/ange.201806992	journal	August 2018
Functionalized Mesoporous Silicas Direct Structural Polymorphism of Amyloid-β Fibrils Lucas, Michael J.; Pan, Henry S.; Verbeke, Eric J. Langmuir, Vol. 36, Issue 26 https://doi.org/10.1021/acs.langmuir.0c00827	journal	June 2020
Reactive Amphiphilic Conjugated Polymers for Inhibiting Amyloid β Assembly Sun, Han; Liu, Jing; Li, Shengliang Angewandte Chemie, Vol. 131, Issue 18 https://doi.org/10.1002/ange.201901459	journal	April 2019
Computational screening of nanoparticles coupling to Aβ40 peptides and fibrils Sen, Soumyo; Vuković, Lela; Král, Petr Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-019-52594-8	journal	November 2019

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