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PMID:22300094

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Citation

Narasimhan, D, Woods, JH and Sunahara, RK (2012) Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction. Future Med Chem 4:137-50

Abstract

Cocaine is highly addictive and there are no pharmacotherapeutic drugs available to treat acute cocaine toxicity or chronic abuse. Antagonizing an inhibitor such as cocaine using a small molecule has proven difficult. The alternative approach is to modify cocaine's pharmacokinetic properties by sequestering or hydrolyzing it in serum and limiting access to its sites of action. We took advantage of a bacterial esterase (CocE) that has evolved to hydrolyze cocaine and have developed it as a therapeutic that rapidly and specifically clears cocaine from the subject. Native enzyme was unstable at 37°C, thus limiting CocE's potential. Innovative computational methods based on the protein's structure helped elucidate its mechanism of destabilization. Novel protein engineering methodologies were applied to substantially improve its stability in vitro and in vivo. These improvements rendered CocE as a powerful and efficacious therapeutic to treat cocaine intoxication and lead the way towards developing a therapy for addiction.

Links

PubMed PMC3290992 Online version:10.4155/fmc.11.194

Keywords

Animals; Bacteria/enzymology; Butyrylcholinesterase/metabolism; Carboxylic Ester Hydrolases/metabolism; Cocaine/metabolism; Cocaine-Related Disorders/enzymology; Cocaine-Related Disorders/therapy; Drug Overdose; Enzyme Stability; Humans; Hydrolysis; Mice; Vaccines/therapeutic use

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:EST2

GO:0004091: carboxylesterase activity

ECO:0000315:

F

This paper describes how the importance of Cocaine esterase and how it can have a positive effect on individuals with an addiction to Cocaine. From this, Figures 1-4 provide necessary information about the annotation.

complete
CACAO 10680

Notes

See also

References

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