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Degradation kinetics of α‐conotoxin TxID
α‐Conotoxin (CTx) TxID is a potent α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been suggested as a potential drug candidate to treat addiction and small cell lung cancer. The function and structure of TxID have been well‐studied, but analyses of its stability have not previousl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722883/ https://www.ncbi.nlm.nih.gov/pubmed/31278882 http://dx.doi.org/10.1002/2211-5463.12697 |
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author | Xu, Pan Xiong, Yang Liu, Yiqiao Yu, Shurun Zhangsun, Dongting Wu, Yong Luo, Sulan |
author_facet | Xu, Pan Xiong, Yang Liu, Yiqiao Yu, Shurun Zhangsun, Dongting Wu, Yong Luo, Sulan |
author_sort | Xu, Pan |
collection | PubMed |
description | α‐Conotoxin (CTx) TxID is a potent α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been suggested as a potential drug candidate to treat addiction and small cell lung cancer. The function and structure of TxID have been well‐studied, but analyses of its stability have not previously been reported. The purpose of this study was to analyze the stability and forced degradation of TxID under various conditions: acid, alkali, water hydrolysis, oxidation, light, thiols, temperature, ionic strength and buffer pH. Different degradation products were formed under various conditions, and the degradation patterns of TxID showed pseudo‐first‐order kinetics. TxID degraded slowest at pH 3 within a pH range of 2–8. The major degradation products were analyzed using liquid chromatography–tandem mass spectrometry and the activity of the main product with α3β4 nAChR was analyzed using electrophysiological methods. Our analysis of TxID stability may aid the selection of appropriate conditions for peptide production, packaging and storage. |
format | Online Article Text |
id | pubmed-6722883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-67228832019-09-10 Degradation kinetics of α‐conotoxin TxID Xu, Pan Xiong, Yang Liu, Yiqiao Yu, Shurun Zhangsun, Dongting Wu, Yong Luo, Sulan FEBS Open Bio Research Articles α‐Conotoxin (CTx) TxID is a potent α3β4 nicotinic acetylcholine receptor (nAChR) antagonist that has been suggested as a potential drug candidate to treat addiction and small cell lung cancer. The function and structure of TxID have been well‐studied, but analyses of its stability have not previously been reported. The purpose of this study was to analyze the stability and forced degradation of TxID under various conditions: acid, alkali, water hydrolysis, oxidation, light, thiols, temperature, ionic strength and buffer pH. Different degradation products were formed under various conditions, and the degradation patterns of TxID showed pseudo‐first‐order kinetics. TxID degraded slowest at pH 3 within a pH range of 2–8. The major degradation products were analyzed using liquid chromatography–tandem mass spectrometry and the activity of the main product with α3β4 nAChR was analyzed using electrophysiological methods. Our analysis of TxID stability may aid the selection of appropriate conditions for peptide production, packaging and storage. John Wiley and Sons Inc. 2019-08-02 /pmc/articles/PMC6722883/ /pubmed/31278882 http://dx.doi.org/10.1002/2211-5463.12697 Text en © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Xu, Pan Xiong, Yang Liu, Yiqiao Yu, Shurun Zhangsun, Dongting Wu, Yong Luo, Sulan Degradation kinetics of α‐conotoxin TxID |
title | Degradation kinetics of α‐conotoxin TxID |
title_full | Degradation kinetics of α‐conotoxin TxID |
title_fullStr | Degradation kinetics of α‐conotoxin TxID |
title_full_unstemmed | Degradation kinetics of α‐conotoxin TxID |
title_short | Degradation kinetics of α‐conotoxin TxID |
title_sort | degradation kinetics of α‐conotoxin txid |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722883/ https://www.ncbi.nlm.nih.gov/pubmed/31278882 http://dx.doi.org/10.1002/2211-5463.12697 |
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