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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...

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Autores principales: Xu, Pan, Xiong, Yang, Liu, Yiqiao, Yu, Shurun, Zhangsun, Dongting, Wu, Yong, Luo, Sulan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
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.
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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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