Influence of Disulfide Connectivity on Structure and Bioactivity of α-Conotoxin TxIA
| العنوان: | Influence of Disulfide Connectivity on Structure and Bioactivity of α-Conotoxin TxIA |
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| المؤلفون: | Sulan Luo, Jinpeng Yu, Xiaopeng Zhu, Yong Wu, Dongting Zhangsun, Xiaosa Wu |
| المصدر: | Molecules, Vol 19, Iss 1, Pp 966-979 (2014) Molecules Volume 19 Issue 1 Pages 966-979 |
| بيانات النشر: | MDPI AG, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Spectrometry, Mass, Electrospray Ionization, Conus textile, Stereochemistry, Pharmaceutical Science, Peptide, Venom, Nicotinic Antagonists, Receptors, Nicotinic, Article, α-conotoxinTxIA, Membrane Potentials, Analytical Chemistry, Cone snail, lcsh:QD241-441, Structure-Activity Relationship, Xenopus laevis, α-conotoxin TxIA, chemistry.chemical_compound, α3β2 nAChRs, lcsh:Organic chemistry, peptide synthesis, Drug Discovery, Peptide synthesis, Animals, Conotoxin, Physical and Theoretical Chemistry, Cells, Cultured, Chromatography, High Pressure Liquid, Ion channel, disulfide isomerisation, chemistry.chemical_classification, Chromatography, Reverse-Phase, biology, Oxidative folding, Organic Chemistry, Conus Snail, biology.organism_classification, Rats, chemistry, Chemistry (miscellaneous), oxidative folding, Cystine, Molecular Medicine, Conotoxins |
| الوصف: | Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs). Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs). Here, we used reversed-phase high performance liquid chromatography (RP-HPLC) and electrospray ionization-mass spectrometry (ESI-MS) to explore the venom peptide diversity of Conus textile, a species of cone snail native to Hainan, China. One fraction of C. textile crude venom potently blocked α3β2 nAChRs. Subsequent purification, synthesis, and tandem mass spectrometric analysis demonstrated that the most active compound in this fraction was identical to α-CTx TxIA, an antagonist of α3β2 nAChRs. Then three disulfide isoforms of α-CTx TxIA were synthesized and their activities were investigated systematically for the first time. As we observed, disulfide isomerisation was particularly important for α-CTx TxIA potency. Although both globular and ribbon isomers showed similar retention times in RP-HPLC, globular TxIA potently inhibited α3β2 nAChRs with an IC50 of 5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had little activity towards α3β2 nAChRs. Two-step oxidation synthesis produced the highest yield of α-CTx TxIA native globular isomer, while a one-step production process based on random oxidation folding was not suitable. In summary, this study demonstrated the relationship between conotoxin activity and disulfide connectivity on α-CTx TxIA. |
| وصف الملف: | application/pdf |
| تدمد: | 1420-3049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b49a589a91d38c09329b8479184f49f8Test https://doi.org/10.3390/molecules19010966Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b49a589a91d38c09329b8479184f49f8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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