Biomimetic affinity purification of cardiotoxin and its pharmacological effects on the nervous system.
Cobra venom is a very precious natural resource. The traditional method for purification of cardiotoxin from cobra venom is a multi-step, high cost, and low recovery procedure. By molecular modeling and docking with SYBYL software, we designed and synthesized an affinity ligand, m-aminobenzoic acid, for high efficiency purification of this therapeutically useful Chinese cobra venom cardiotoxin. The one-step recovery of cardiotoxin reached 64% and the purity reached 92% upon purification. The binding capacity of this synthetic ligand was 9.1 mg cardiotoxin/g moist weight gel and the affinity constant for cardiotoxin was 5.5 x 10(3) M(-1). Unlike a natural affinity ligand, this synthetic ligand is highly stable, and has great potential for industrial scale production of cardiotoxin. In addition, we examined the effects of cardiotoxin on the nervous system in a mouse model. Results showed that cardiotoxin could maintain analgesic effects for 120 min with a dose of less than 0.06 mg/kg (2.8% of the LD(50)). Administration of 0.12 mg/kg cardiotoxin could improve scopolamine impairments of memory in mice. These results suggest that cardiotoxin may be a potential drug for nervous system diseases.
Dong
Dexian
D
MOE Key Laboratory of Microbial Metabolism, College of Life Science and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Liu
Haoran
H
Xiao
Qishi
Q
Wang
Ting
T
Liu
Huaqing
H
Li
Rongxiu
R
D062365:Aminobenzoates / Q000737:chemistry; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D040761:Biomimetic Materials / Q000378:metabolism*; D054715:Cardiotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002846:Chromatography, Affinity; D007700:Kinetics; D008024:Ligands; D008568:Memory / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D009420:Nervous System / Q000187:drug effects*; D010147:Pain Measurement
D062365:Aminobenzoates; D000700:Analgesics; D054715:Cardiotoxins; D008024:Ligands