Abstract
Enhancing cocaine metabolism by administration of cocaine esterase (CocE) has been recognized as a promising treatment strategy for cocaine overdose and addiction, because CocE is the most efficient native enzyme for metabolizing the naturally occurring cocaine yet identified. A major obstacle to the clinical application of CocE is the thermoinstability of native CocE with a half-life of only a few minutes at physiological temperature (37°C). Here we report thermostable variants of CocE developed through rational design using a novel computational approach followed by in vitro and in vivo studies. This integrated computational-experimental effort has yielded a CocE variant with a ∼30-fold increase in plasma half-life both in vitro and in vivo. The novel design strategy can be used to develop thermostable mutants of any protein.
Original language | English (US) |
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Pages (from-to) | 318-323 |
Number of pages | 6 |
Journal | Molecular pharmacology |
Volume | 75 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2009 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology