8 research outputs found
Anti-Cocaine Compositions and Treatment
Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides
Anti-Cocaine Compositions and Treatment
Embodiments of the invention disclosed herein generally relate to anti-cocaine therapeutics. Specifically, some embodiments of the invention relate to highly efficient, thermostable, and long-lasting cocaine esterase (CocE) mutants that can protect against the toxic and reinforcing effects of cocaine in subjects. Provided herein are mutant CocE polypeptides displaying thermostable esterase activity. Also provided are methods of treating cocaine-induced conditions in a subject in need via administration of mutant CocE as well as methods for high-throughput screening of candidate esterase polypeptides
Cocaine Esterase Prevents Cocaine-Induced Toxicity and the Ongoing Intravenous Self-Administration of Cocaine in Rats
Thermostable Variants of Cocaine Esterase for Long-Time Protection against Cocaine Toxicity
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