毒理性
用丁二酸酐对产气荚膜梭菌epsilon原毒素或毒素进行修饰,导致它们分别对胰蛋白酶的激活作用或致死活性丧失。原毒素对丁酰化反应的敏感性高于毒素。另一方面,丁酰化的原毒素可以被胰凝乳蛋白酶激活和切割,但胰蛋白酶不能。毒素的致死活性在用2,3-二甲基马来酸酐或2,4,6-三硝基苯磺酸处理后也丧失了。当用2,3-二甲基马来酸酐处理的毒素再用丁二酸酐或2,4,6-三硝基苯磺酸处理后,在酸性条件下孵化,它又恢复了致死活性。因此,修饰氨基(赖氨酸残基)阻止了胰蛋白酶对原毒素的激活,并消除了毒素的致死活性。
Modification with succinic anhydride of Clostridium perfringens epsilon prototoxin or toxin resulted in a loss of activation by trypsin or lethal activity, respectively. The prototoxin was more sensitive to succinylation than the toxin. On the other hand, the succinylated prototoxin was activated and cleaved by chymotrypsin, but not by trypsin. The lethal activity of the toxin was also lost after treatment with 2,3-dimethylmaleic anhydride or 2,4,6-trinitrobenzenesulfonic acid. When the 2,3-dimethylmaleic anhydride treated toxin treated with succinic anhydride or 2,4,6-trinitrobenzenesulfonic acid was incubated under acidic condition, it regained lethal activity. Thus modification of amino groups (lysine residues) prevented activation of the prototoxin by trypsin, and abolished lethal activity of the toxin.
来源:Hazardous Substances Data Bank (HSDB)