| Literature DB >> 23297221 |
Denis G Ilyushin1, Ivan V Smirnov, Alexey A Belogurov, Igor A Dyachenko, Tatiana Iu Zharmukhamedova, Tatjana I Novozhilova, Eugene A Bychikhin, Marina V Serebryakova, Oleg N Kharybin, Arkadii N Murashev, Konstantin A Anikienko, Eugene N Nikolaev, Natalia A Ponomarenko, Dmitry D Genkin, G Michael Blackburn, Patrick Masson, Alexander G Gabibov.
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.Entities:
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Year: 2013 PMID: 23297221 PMCID: PMC3557082 DOI: 10.1073/pnas.1211118110
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN: 0027-8424 Impact factor: 11.205