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Effects of serum, enzyme, thiol, and forced degradation on the stabilities of αO‐Conotoxin GeXIVA[1,2] and GeXIVA [1,4]
Author(s) -
Yu Shurun,
Wu Yong,
Xu Pan,
Wang Shuai,
Zhangsun Dongting,
Luo Sulan
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13167
Subject(s) - chemistry , thiol , biochemistry
αO‐conotoxin Ge XIVA , which is a potent antagonist of α9α10 nicotinic acetylcholine receptor ( nAChR ), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both Ge XIVA [1,2] and Ge XIVA [1,4] showed similar low nanomolar IC 50 s in potent blocking rat α9α10 nAChR s. Here, we first reported stabilities of Ge XIVA [1,2] and Ge XIVA [1,4] in various biochemical circumstances, including human serum, enzymatic degradation, and thiol, which would be the key factors to affect stabilities of the two isomers in vivo. Simultaneously, forced degradation was carried out to evaluate stabilities of the two isomers. Ge XIVA [1,2] and Ge XIVA [1,4] were unstable when they were incubated in serum and digestive enzymes at 37°C. Their disulfide bond frameworks were easy to be scrambled in GSH and HSA . For different stress conditions, their stabilities were impacted greatly by oxidation, temperature, and alkaline conditions. The results may provide a foundation for storage conditions, structural modification, and pharmaceutical preparation of Ge XIVA [1,2] and Ge XIVA [1,4].