Degradation kinetics of α‐conotoxin TxID

Abstract

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.

Prevention of scar hyperplasia in the skin by conotoxin: A prospective review

“…They can specifically inhibit muscle-type nicotinic acetylcholine receptors, causing organ numbness, vomiting, dizziness, respiratory failure, and death. [29][30][31]…”

“…Notably, GI and MI are the most toxic of the α‐conotoxin acting on the muscle‐type acetylcholine receptors. They can specifically inhibit muscle‐type nicotinic acetylcholine receptors, causing organ numbness, vomiting, dizziness, respiratory failure, and death 29‐31 …”

α-Conotoxin TxID and [S9K]TxID, α3β4 nAChR Antagonists, Attenuate Expression and Reinstatement of Nicotine-Induced Conditioned Place Preference in Mice

“…To further improve the selectivity of TxID, the researchers used a series of non-natural amino acids to substitute Serine at position 9 of TxID and found that [S9K]TxID displayed a specific and potent inhibitory effect towards α3β4 nAChRs with an IC 50 of 6.9 nM [ 16 ]. The stabilities of TxID under multiple conditions were evaluated by UPLC based on recommendation of International Conference on Harmonization [ 17 ]. The purpose of the present study was to evaluate the effect of α3β4 nAChRs antagonists TxID and [S9K]TxID in nicotine-induced behaviors, by investigating whether TxID and [S9K]TxID would alter the acquisition and relapse of nicotine-induced CPP, and physical acute nicotine behaviors in mice.…”