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Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1243-8. doi: 10.1073/pnas.1211118110. Epub 2013 Jan 7.

Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo.

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1
Institute of Bioorganic Chemistry Russian Academy of Sciences, 117997 Moscow, Russia.

Abstract

The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD(50) of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior.

PMID:
23297221
PMCID:
PMC3557082
DOI:
10.1073/pnas.1211118110
[Indexed for MEDLINE]
Free PMC Article
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