期刊
CHEMICAL BIOLOGY & DRUG DESIGN
卷 91, 期 5, 页码 1030-1041出版社
WILEY
DOI: 10.1111/cbdd.13167
关键词
O-conotoxin GeXIVA[1,2] and GeXIVA[1,4]; enzymatic degradation; forced degradation; serum; stabilities; thiol
资金
- National Natural Science Foundation of China [81420108028, 81660585]
- Changjiang Scholars and Innovative Research Team in University [IRT_15R15]
- Major Science and Technology Project of Hainan Province [ZDKJ2016002]
O-conotoxin GeXIVA, which is a potent antagonist of 910 nicotinic acetylcholine receptor (nAChR), is of great interest as a potential analgesic for chronic neuropathic pain. It has three isomers, of which both GeXIVA[1,2] and GeXIVA[1,4] showed similar low nanomolar IC(50)s in potent blocking rat 910 nAChRs. Here, we first reported stabilities of GeXIVA[1,2] and GeXIVA[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. GeXIVA[1,2] and GeXIVA[1,4] were unstable when they were incubated in serum and digestive enzymes at 37 degrees 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 GeXIVA[1,2] and GeXIVA[1,4].
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