Modulation of polypeptide conformation through donor–acceptor transformation of side-chain hydrogen bonding ligands
| Autor: | Hua He, Yinzhao Huang, Yao Lin, Xiaochu Ba, Yun Liu, Deepak Mani, Ryan Baumgartner, Andrew L. Ferguson, Lichen Yin, Nan Zheng, Mu-Ping Nieh, Jianjun Cheng, Ziyuan Song, Kuo-Chih Shih, Rachael A. Mansbach |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Models
Molecular Protein Conformation alpha-Helical Conformational change Protein Conformation Stereochemistry Science Triazole General Physics and Astronomy Ionic bonding Protonation Nanotechnology 02 engineering and technology Ligands 010402 general chemistry 01 natural sciences Article Protein Structure Secondary General Biochemistry Genetics and Molecular Biology Mice chemistry.chemical_compound Biopolymers Protein structure Side chain Animals Humans chemistry.chemical_classification Microscopy Confocal Multidisciplinary Hydrogen bond Spectrum Analysis Hydrogen Bonding General Chemistry Polymer Hydrogen-Ion Concentration Triazoles 021001 nanoscience & nanotechnology 0104 chemical sciences chemistry NIH 3T3 Cells Peptides 0210 nano-technology HeLa Cells |
| Zdroj: | Nature Communications, Vol 8, Iss 1, Pp 1-8 (2017) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Hydrogen bonding plays a major role in determining the tridimensional structure of biopolymers. Here, the authors show that control over a polypeptide conformation can be achieved by altering the donor-acceptor properties of side-chain triazole units via protonation-deprotonation. |
| Databáze: | OpenAIRE |
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