| Title : Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo - Ilyushin_2013_Proc.Natl.Acad.Sci.U.S.A_110_1243 |
| Author(s) : Ilyushin DG , Smirnov IV , Belogurov AA, Jr. , Dyachenko IA , Zharmukhamedova T , Novozhilova TI , Bychikhin EA , Serebryakova MV , Kharybin ON , Murashev AN , Anikienko KA , Nikolaev EN , Ponomarenko NA , Genkin DD , Blackburn GM , Masson P , Gabibov AG |
| Ref : Proc Natl Acad Sci U S A , 110 :1243 , 2013 |
|
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. |
| PubMedSearch : Ilyushin_2013_Proc.Natl.Acad.Sci.U.S.A_110_1243 |
| PubMedID: 23297221 |
Ilyushin DG, Smirnov IV, Belogurov AA, Jr., Dyachenko IA, Zharmukhamedova T, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybin ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG (2013)
Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo
Proc Natl Acad Sci U S A
110 :1243
Ilyushin DG, Smirnov IV, Belogurov AA, Jr., Dyachenko IA, Zharmukhamedova T, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybin ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG (2013)
Proc Natl Acad Sci U S A
110 :1243