Bacterial cocaine esterase: a protein-based therapy for cocaine overdose and addiction

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