Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

Disclosed are a cocaine esterase mutant and use thereof. The cocaine esterase mutant is obtained by mutating a wildtype cocaine esterase, an amino acid sequence of the wildtype cocaine esterase is shown as SEQ ID No.1, the cocaine esterase mutant is T172R/G173Q/L196C/I301C, or additionally added with V116K point mutation, or additionally added with A51 site mutation, and the A51 site mutation is L, Y, V, F or W. Catalytic efficiency of the cocaine esterase mutant screened on a cocaine toxic metabolite benzoylecgonine is greatly improved compared with that of a wildtype enzyme.

Provided are mutant cocaine esterase polypeptides and PEGylated formulations thereof.

The Bacterial cocaine esterase (CocE) mutants disclosed herein each have enhanced catalytic efficiency for ()-cocaine, as compared to CocE mutants in the prior art, including CocE mutant E172-173. The presently-disclosed subject matter further includes a pharmaceutical composition including a mutant of bacterial cocaine hydrolase, as described herein, and a suitable pharmaceutical carrier. The presently-disclosed subject matter further includes a method of treating a cocaine-induced condition comprising administering to an individual an effective amount of a mutant of bacterial cocaine hydrolase variant, as disclosed herein, to accelerate cocaine metabolism and produce biologically inactive metabolites.

Disclosed are a cocaine esterase mutant and use thereof. The cocaine esterase mutant is obtained by mutating a wildtype cocaine esterase, an amino acid sequence of the wildtype cocaine esterase is shown as SEQ ID No. 1, the cocaine esterase mutant is T172R/G173Q/L196C/I301C, or additionally added with V116K point mutation, or additionally added with A51 site mutation, and the A51 site mutation is L, Y, V, F or W. Catalytic efficiency of the cocaine esterase mutant screened on a cocaine toxic metabolite benzoylecgonine is greatly improved compared with that of a wildtype enzyme.

Provided are compositions comprising a cocaine esterase (CocE) and a compound that thermostabilizes the CocE. Also provided are methods of thermostabilizing a cocaine esterase. Additionally provided are methods of treating a mammal undergoing a cocaine-induced condition. Methods of determining whether a compound is a thermostabilizing agent for a protein are also provided. Uses of the above-described compositions for the treatment of a cocaine-induced condition is additionally provided. Additionally provided is an isolated nucleic acid encoding a CocE polypeptide having the substitutions L169K and G173Q, and the CocE polypeptide encoded by that nucleic acid, and pharmaceutical compositions thereof. Further provided is the use of that composition for the manufacture of a medicament for the treatment of a cocaine-induced condition and for the treatment of a cocaine-induced condition.

Disclosed herein are compositions, methods, and articles of personal protective equipment for use in detoxifying an organophosphate-based agent, wherein the compositions, methods, and articles comprise contacting the organophosphate-based agent with a cocaine esterase, wherein the contacting detoxifies the organophosphate-based agent.