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

Denis G. Ilyushin, 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

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

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 LD50 of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior.

Original languageEnglish
Pages (from-to)1243-1248
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number4
DOIs
Publication statusPublished - 22 Jan 2013
Externally publishedYes

Fingerprint

Dive into the research topics of 'Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo'. Together they form a unique fingerprint.

Cite this