Chemical modification of cationic groups of a novel alpha-neurotoxin (Oh-4) from king cobra (Ophiophagus hannah) venom.
The cationic groups of arginine and lysine residues in Oh-4, a novel alpha-neurotoxin from king cobra (Ophiophagus hannah) venom were subjected to modification with p-hydroxyphenylglyoxal (HPG) and trinitrobenzene sulfonate (TNBS), respectively. Monoderivatization of Arg-35, resulted in a drastic loss in neurotoxicity to 25% of the native toxin. The activity was decreased to a greater extent with the derivative extensively modified on Arg-35, -9, and -37. The Arg-35-modified derivative retained about a half of the antigenicity of the native toxin, and extensive modification on Arg-9 and Arg-37 caused a further decrease in the antigenicity of the toxin molecule. Selective trinitrophenylation (TNP-) of Lys-51 caused losses of neurotoxicity and antigenicity by 77 and 83%, respectively. These results indicate that Arg-35 and Lys-51 in Oh-4 have important roles in the neurotoxicity. In contrast to the Arg residues at 9, 35, and 37, Lys-51 plays a more critical role in the antigenicity.
School of Chemistry, Kaohsiung Medical College, Taiwan.
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Lin
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Chi
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Chang
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Kuo
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Chang
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002412:Cations; D002851:Chromatography, High Pressure Liquid; D004546:Elapid Venoms / Q000737:chemistry*; D005260:Female; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009498:Neurotoxins / Q000737:chemistry* / Q000633:toxicity; D010449:Peptide Mapping
D000596:Amino Acids; D002412:Cations; D004546:Elapid Venoms; D009498:Neurotoxins