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Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels
Protein aggregation is a process by which misfolded proteins polymerizes into aggregates and forms fibrous structures with a β-sheet conformation, known as amyloids. It is an undesired outcome, as it not only causes numerous neurodegenerative diseases, but is also a major deterrent in the developmen...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379557/ https://www.ncbi.nlm.nih.gov/pubmed/28374820 http://dx.doi.org/10.1038/srep45777 |
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author | Rajan, Robin Matsumura, Kazuaki |
author_facet | Rajan, Robin Matsumura, Kazuaki |
author_sort | Rajan, Robin |
collection | PubMed |
description | Protein aggregation is a process by which misfolded proteins polymerizes into aggregates and forms fibrous structures with a β-sheet conformation, known as amyloids. It is an undesired outcome, as it not only causes numerous neurodegenerative diseases, but is also a major deterrent in the development of protein biopharmaceuticals. Here, we report a rational design for the synthesis of novel zwitterionic polymer-based core-shell nanogels via controlled radical polymerization. Nanogels with different sizes and functionalities in the core and shell were prepared. The nanogels exhibit remarkable efficiency in the protection of lysozyme against aggregation. Addition of nanogels suppresses the formation of toxic fibrils and also enables lysozyme to retain its enzymatic activity. Increasing the molecular weight and degree of hydrophobicity markedly increases its overall efficiency. Investigation of higher order structures revealed that lysozyme when heated without any additive loses its secondary structure and transforms into a random coil conformation. In contrast, presence of nanogels facilitates the retention of higher order structures by acting as molecular chaperones, thereby reducing molecular collisions. The present study is the first to show that it is possible to design zwitterionic nanogels using appropriate polymerization techniques that will protect proteins under conditions of extreme stress and inhibit aggregation. |
format | Online Article Text |
id | pubmed-5379557 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53795572017-04-07 Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels Rajan, Robin Matsumura, Kazuaki Sci Rep Article Protein aggregation is a process by which misfolded proteins polymerizes into aggregates and forms fibrous structures with a β-sheet conformation, known as amyloids. It is an undesired outcome, as it not only causes numerous neurodegenerative diseases, but is also a major deterrent in the development of protein biopharmaceuticals. Here, we report a rational design for the synthesis of novel zwitterionic polymer-based core-shell nanogels via controlled radical polymerization. Nanogels with different sizes and functionalities in the core and shell were prepared. The nanogels exhibit remarkable efficiency in the protection of lysozyme against aggregation. Addition of nanogels suppresses the formation of toxic fibrils and also enables lysozyme to retain its enzymatic activity. Increasing the molecular weight and degree of hydrophobicity markedly increases its overall efficiency. Investigation of higher order structures revealed that lysozyme when heated without any additive loses its secondary structure and transforms into a random coil conformation. In contrast, presence of nanogels facilitates the retention of higher order structures by acting as molecular chaperones, thereby reducing molecular collisions. The present study is the first to show that it is possible to design zwitterionic nanogels using appropriate polymerization techniques that will protect proteins under conditions of extreme stress and inhibit aggregation. Nature Publishing Group 2017-04-04 /pmc/articles/PMC5379557/ /pubmed/28374820 http://dx.doi.org/10.1038/srep45777 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Rajan, Robin Matsumura, Kazuaki Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title | Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title_full | Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title_fullStr | Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title_full_unstemmed | Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title_short | Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
title_sort | inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5379557/ https://www.ncbi.nlm.nih.gov/pubmed/28374820 http://dx.doi.org/10.1038/srep45777 |
work_keys_str_mv | AT rajanrobin inhibitionofproteinaggregationbyzwitterionicpolymerbasedcoreshellnanogels AT matsumurakazuaki inhibitionofproteinaggregationbyzwitterionicpolymerbasedcoreshellnanogels |