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Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands
Synthetic polypeptides have received increasing attention due to their ability to form higher ordered structures similar to proteins. The control over their secondary structures, which enables dynamic conformational changes, is primarily accomplished by tuning the side-chain hydrophobic or ionic int...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522480/ https://www.ncbi.nlm.nih.gov/pubmed/28733648 http://dx.doi.org/10.1038/s41467-017-00079-5 |
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author | Song, Ziyuan Mansbach, Rachael A. He, Hua Shih, Kuo-Chih Baumgartner, Ryan Zheng, Nan Ba, Xiaochu Huang, Yinzhao Mani, Deepak Liu, Yun Lin, Yao Nieh, Mu-Ping Ferguson, Andrew L. Yin, Lichen Cheng, Jianjun |
author_facet | Song, Ziyuan Mansbach, Rachael A. He, Hua Shih, Kuo-Chih Baumgartner, Ryan Zheng, Nan Ba, Xiaochu Huang, Yinzhao Mani, Deepak Liu, Yun Lin, Yao Nieh, Mu-Ping Ferguson, Andrew L. Yin, Lichen Cheng, Jianjun |
author_sort | Song, Ziyuan |
collection | PubMed |
description | Synthetic polypeptides have received increasing attention due to their ability to form higher ordered structures similar to proteins. The control over their secondary structures, which enables dynamic conformational changes, is primarily accomplished by tuning the side-chain hydrophobic or ionic interactions. Herein we report a strategy to modulate the conformation of polypeptides utilizing donor–acceptor interactions emanating from side-chain H-bonding ligands. Specifically, 1,2,3-triazole groups, when incorporated onto polypeptide side-chains, serve as both H-bond donors and acceptors at neutral pH and disrupt the α-helical conformation. When protonated, the resulting 1,2,3-triazolium ions lose the ability to act as H-bond acceptors, and the polypeptides regain their α-helical structure. The conformational change of triazole polypeptides in response to the donor-acceptor pattern was conclusively demonstrated using both experimental-based and simulation-based methods. We further showed the utility of this transition by designing smart, cell-penetrating polymers that undergo acid-activated endosomal escape in living cells. |
format | Online Article Text |
id | pubmed-5522480 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55224802017-07-28 Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands Song, Ziyuan Mansbach, Rachael A. He, Hua Shih, Kuo-Chih Baumgartner, Ryan Zheng, Nan Ba, Xiaochu Huang, Yinzhao Mani, Deepak Liu, Yun Lin, Yao Nieh, Mu-Ping Ferguson, Andrew L. Yin, Lichen Cheng, Jianjun Nat Commun Article Synthetic polypeptides have received increasing attention due to their ability to form higher ordered structures similar to proteins. The control over their secondary structures, which enables dynamic conformational changes, is primarily accomplished by tuning the side-chain hydrophobic or ionic interactions. Herein we report a strategy to modulate the conformation of polypeptides utilizing donor–acceptor interactions emanating from side-chain H-bonding ligands. Specifically, 1,2,3-triazole groups, when incorporated onto polypeptide side-chains, serve as both H-bond donors and acceptors at neutral pH and disrupt the α-helical conformation. When protonated, the resulting 1,2,3-triazolium ions lose the ability to act as H-bond acceptors, and the polypeptides regain their α-helical structure. The conformational change of triazole polypeptides in response to the donor-acceptor pattern was conclusively demonstrated using both experimental-based and simulation-based methods. We further showed the utility of this transition by designing smart, cell-penetrating polymers that undergo acid-activated endosomal escape in living cells. Nature Publishing Group UK 2017-07-21 /pmc/articles/PMC5522480/ /pubmed/28733648 http://dx.doi.org/10.1038/s41467-017-00079-5 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Song, Ziyuan Mansbach, Rachael A. He, Hua Shih, Kuo-Chih Baumgartner, Ryan Zheng, Nan Ba, Xiaochu Huang, Yinzhao Mani, Deepak Liu, Yun Lin, Yao Nieh, Mu-Ping Ferguson, Andrew L. Yin, Lichen Cheng, Jianjun Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title | Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title_full | Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title_fullStr | Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title_full_unstemmed | Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title_short | Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
title_sort | modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522480/ https://www.ncbi.nlm.nih.gov/pubmed/28733648 http://dx.doi.org/10.1038/s41467-017-00079-5 |
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