Makhnyr' V M, Kozlovskaia E P
Bioorg Khim. 1990 May;16(5):643-8.
The influence of chemical modification on neurotoxin RTX-III toxicity in mice has been studied. The toxicity was not affected by modification of Trp30 residue with 2-hydroxy-5-nitrobenzyl bromide but was diminished by a factor of 100 after reduction of the toxin's two disulfide bonds with 2-mercaptoethanol followed by derivatization with iodoacetamide. Blocking carboxyl groups with [3H]glycine methyl ester in the presence of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide led to only a two-fold drop in toxicity in the case of monocarboxylate-modified derivatives and a six-fold decrease for dimodified derivatives. A conception of multipoint attachment of the toxin to sodium channel is discussed.
研究了化学修饰对小鼠神经毒素RTX-III毒性的影响。用2-羟基-5-硝基苄基溴修饰色氨酸30残基对毒性没有影响,但用2-巯基乙醇还原毒素的两个二硫键,然后用碘乙酰胺衍生化后,毒性降低了100倍。在1-乙基-3-(3-二甲基氨基丙基)碳二亚胺存在下,用[3H]甘氨酸甲酯封闭羧基,单羧酸盐修饰的衍生物毒性仅下降两倍,双修饰的衍生物毒性下降六倍。讨论了毒素与钠通道多点结合的概念。