Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors

ZHANGSUN Dongting; ZHU Xiaopeng; WU Yong; HU Yuanyan; BING Hui; LUO Sulan

doi:10.11665/j.issn.1000-5048.20160416

Journal of China Pharmaceutical University > 2016 > 47(4): 483-490. > DOI: 10.11665/j.issn.1000-5048.20160416

ZHANGSUN Dongting, ZHU Xiaopeng, WU Yong, HU Yuanyan, BING Hui, LUO Sulan. Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors[J]. Journal of China Pharmaceutical University, 2016, 47(4): 483-490. DOI: 10.11665/j.issn.1000-5048.20160416

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Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors

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Abstract

To investigate activities of three isomers of α-conotoxin TxID on human α3β4 and α6/α3β4 nicotinic acetylcholine receptors(nAChRs). The three isomers of α-conotoxin TxID were synthesized using solid phase Fmoc chemistry and fully folded by two-step oxidations. Human α3β4 and α6/α3β4 nAChRs were expressed in oocytes of Xenopus laevis, which were used for bioassay of the three isomers, including inhibition and washout reversibility. There were obvious differences between the inhibition potency of each isomers at human α3β4 and α6/α3β4 nAChRs. The blocking was reversible and washout rapidly. The most potent isomer is the globular form with an IC₅₀ of 9. 3 nmol/L on human α3β4 and α6/α3β4 nAChRs respectively. The 2nd potent isomer was the ribbon form with much less potency, which had an IC₅₀ of > 5 μmol/L. The bead isomer had little or no block on human α3β4 and α6/α3β4 nAChRs with an IC₅₀ of > 10 μmol/L. The three isomers of α-conotoxin TxID were synthesized successfully with two pairs of desired disulfide bond. Inhibition activities of the 3 isomers on human α3β4 and α6/α3β4 nAChRs were obtained respectively, which would be basis for new marine drug development of α-conotoxin TxID.
- α-conotoxin TxID,
- disulfide bond isomers,
- peptide synthesis,
- human α3β4 nAChRs,
- human α6/α3β4 nAChRs

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