Uses of modified cholinesterase and compositions containing them.

摘要

Detoxification of humans who have been exposed to phosphylating agents, and decontamination of a locus containing phosphylating agents (e.g. organophosphorus insecticides or organophosphorus nerve gases), are effected by administration to the humans or applying to the locus, respectively, at least one recombinant cholinesterase mutant so as to form phosphylated cholinesterase mutant, in presence of intrinsic or extrinsic reactivator activity effective to reactivate the mutant by breaking the phosphyl/cholinesterase mutant covalent bond, the phosphylated mutant being more readily reconverted to nonphosphylated mutant, than the corresponding phosphylated non-mutated cholinesterase is reconverted to non-phosphylated non-mutated cholinesterase. Mutation sites in the amino acid sequence of HuAChE, or in equivalent positions in other cholinesterases, are preferably selected from at least one of (a) Ser2 @ @ 3, Glu334, His447; (b) Gly122, Tyr133, Glu2 @ @ 2, Ser229, Gly448, Glu45 @ @ ; (c) Leu76, Tyr77, Trp86, Tyr117, Tyr119, Gly12 @ @ , Gly121, Trp236, Phe295, Phe297, Tyr337, Phe338, Trp439, Tyr449; and/or (d) Tyr72, Asp74, Tyr124, Glu285, Trp286, Tyr341. The invention includes use of the (non-phosphylated) mutants for the manufacture of medicaments for detoxification, pharmaceutical formulations for detoxification, compositions for decontamination, and phosphylated and non-phosphylated recombinant cholinesterase mutants, per se.