ArticleBMC biotechnology2008
Substantially improved pharmacokinetics of recombinant human butyrylcholinesterase by fusion to human serum albumin.
Article in BMC biotechnology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 60 citations in OpenAlex.
- Counteracting poisoning with chemical warfare nerve agents.Arhiv za higijenu rada i toksikologiju · 2020Review
- Development of a long-acting Fc-fused cocaine hydrolase with improved yield of protein expression.Chemico-biological interactions · 2019Article
- Resurrection and Reactivation of Acetylcholinesterase and Butyrylcholinesterase.Chemistry (Weinheim an der Bergstrasse, Germany) · 2019Review
- Development of Fc-Fused Cocaine Hydrolase for Cocaine Addiction Treatment: Catalytic and Pharmacokinetic Properties.The AAPS journal · 2018Article
- Synthesis and study on activity in vitro of the high purity human butyrylcholinesterase conjugated with gold nanoparticles.Doklady. Biochemistry and biophysics · 2016Article
- Fusion protein of single-chain variable domain fragments for treatment of myasthenia gravis.Neural regeneration research · 2014Article
- Recent advances in the treatment of organophosphorous poisonings.Iranian journal of medical sciences · 2012Article
- Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa.BMC biotechnology · 2011Article
- Post-exposure therapy with recombinant human BuChE following percutaneous VX challenge in guinea-pigs.Toxicology letters · 2011Article
- Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging.The Journal of biological chemistry · 2011Article
- Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.Archives of biochemistry and biophysics · 2010Review
- Recent progress in protein drug design and discovery with a focus on novel approaches to the development of anti-cocaine medications.Future medicinal chemistry · 2009Review
- Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings.Acta naturae · 2009Article
- Addition of a sequence from alpha2-antiplasmin transforms human serum albumin into a blood clot component that speeds clot lysis.BMC biotechnology · 2009Article
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Authors and funding
23 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman butyrylcholinesterase (huBChE) has been shown to be an effective antidote against multiple LD50 of organophosphorus compounds. A prerequisite for such use of huBChE is a prolonged circulatory half-life. This study was undertaken to produce recombinant huBChE fused to human serum albumin (hSA) and characterize the fusion protein.
resultsSecretion level of the fusion protein produced in vitro in BHK cells was approximately 30 mg/liter. Transgenic mice and goats generated with the fusion constructs expressed in their milk a bioactive protein at concentrations of 0.04-1.1 g/liter. BChE activity gel staining and a size exclusion chromatography (SEC)-HPLC revealed that the fusion protein consisted of predominant dimers and some monomers. The protein was confirmed to have expected molecular mass of approximately 150 kDa by Western blot. The purified fusion protein produced in vitro was injected intravenously into juvenile pigs for pharmacokinetic study. Analysis of a series of blood samples using the Ellman assay revealed a substantial enhancement of the plasma half-life of the fusion protein (approximately 32 h) when compared with a transgenically produced huBChE preparation containing >70% tetramer (approximately 3 h). In vitro nerve agent binding and inhibition experiments indicated that the fusion protein in the milk of transgenic mice had similar inhibition characteristics compared to human plasma BChE against the nerve agents tested.
conclusionBoth the pharmacokinetic study and the in vitro nerve agent binding and inhibition assay suggested that a fusion protein retaining both properties of huBChE and hSA is produced in vitro and in vivo. The production of the fusion protein in the milk of transgenic goats provided further evidence that sufficient quantities of BChE/hSA can be produced to serve as a cost-effective and reliable source of BChE for prophylaxis and post-exposure treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.