Activities of α-conotoxin TxID isomers on human nicotinic acetylcholine receptors
10.11665/j.issn.1000-5048.20160416
- VernacularTitle:α-芋螺毒素TxID异构体对人类乙酰胆碱受体的活性研究
- Author:
Dongting ZHANGSUN
1
;
Xiaopeng ZHU
;
Yong WU
;
Yuanyan HU
;
Hui BING
;
Sulan LUO
Author Information
1. 海南大学热带生物资源教育部重点实验室、海口市海洋药物重点实验室
- Publication Type:Journal Article
- Keywords:
α-conotoxin TxID;
disulfide bond isomers;
peptide synthesis;
human α3β4 nAChRs;
human α6/α3β4 nAChRs
- From:
Journal of China Pharmaceutical University
2016;47(4):483-490
- CountryChina
- Language:Chinese
-
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.
