ArticleThe Biochemical journal1998
Modulation of circulatory residence of recombinant acetylcholinesterase through biochemical or genetic manipulation of sialylation levels.
Article in The Biochemical journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 65 citations in OpenAlex.
- Strategies for Glycoengineering Therapeutic Proteins.Frontiers in chemistry · 2022Review
- Production, purification and characterization of recombinant human R-spondin1 (RSPO1) protein stably expressed in human HEK293 cells.BMC biotechnology · 2020Article
- Cholinesterases and the fine line between poison and remedy.Biochemical pharmacology · 2018Review
- Recombinant human heterodimeric IL-15 complex displays extensive and reproducible N- and O-linked glycosylation.Glycoconjugate journal · 2016Article
- Quantification of Plasmodium-host protein interactions on intact, unmodified erythrocytes by back-scattering interferometry.Malaria journal · 2015Article
- Interaction of acetylcholinesterase with neurexin-1β regulates glutamatergic synaptic stability in hippocampal neurons.Molecular brain · 2014Article
- Article
- Biological Insights into Therapeutic Protein Modifications throughout Trafficking and Their Biopharmaceutical Applications.International journal of cell biology · 2013Article
- Glycosylation of therapeutic proteins: an effective strategy to optimize efficacy.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2010Review
- Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings.Acta naturae · 2009Article
- Engineering complex-type N-glycosylation in Pichia pastoris using GlycoSwitch technology.Nature protocols · 2009Article
- Crystallization and X-ray structure of full-length recombinant human butyrylcholinesterase.Acta crystallographica. Section F, Structural biology and crystallization communications · 2007Article
- LARGE SCALE PURIFICATION OF BUTYRYLCHOLINESTERASE FROM HUMAN PLASMA SUITABLE FOR INJECTION INTO MONKEYS; A POTENTIAL NEW THERAPEUTIC FOR PROTECTION AGAINST COCAINE AND NERVE AGENT TOXICITY.The journal of medical, chemical, biological, and radiological defense · 2005Article
- In vivo synthesis of mammalian-like, hybrid-type N-glycans in Pichia pastoris.Applied and environmental microbiology · 2004Article
- Amino acid domains control the circulatory residence time of primate acetylcholinesterases in rhesus macaques (Macaca mulatta).The Biochemical journal · 2004Article
- A transgenic insect cell line engineered to produce CMP-sialic acid and sialylated glycoproteins.Glycobiology · 2003Article
- Overloading and removal of N-glycosylation targets on human acetylcholinesterase: effects on glycan composition and circulatory residence time.The Biochemical journal · 2002Article
- Effect of chemical modification of recombinant human acetylcholinesterase by polyethylene glycol on its circulatory longevity.The Biochemical journal · 2001Article
- Effect of human acetylcholinesterase subunit assembly on its circulatory residence.The Biochemical journal · 2001Article
- Hydration change during the aging of phosphorylated human butyrylcholinesterase: importance of residues aspartate-70 and glutamate-197 in the water network as probed by hydrostatic and osmotic pressures.The Biochemical journal · 1999Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sialylation of N-glycans associated with recombinant human acetylcholinesterase (rHuAChE) has a central role in determining its circulatory clearance rate. Human embryonal kidney 293 (HEK-293) cells, which are widely used for the expression of recombinant proteins, seem to be limited in their ability to sialylate overexpressed rHuAChE. High-resolution N-glycan structural analysis, by gel permeation, HPLC anion-exchange chromatography and high-pH anion-exchange chromatography (HPAEC), revealed that the N-glycans associated with rHuAChE produced in HEK-293 cells belong mainly to the complex-biantennary class and are only partly sialylated, with approx. 60% of the glycans being monosialylated. This partial sialylation characterizes rHuAChE produced by cells selected for high-level expression of the recombinant protein. In low-level producer lines, the enzyme exhibits a higher sialic acid content, suggesting that undersialylation of rHuAChE in high-level producer lines stems from a limited endogenous glycosyltransferase activity. To improve sialylation in HEK-293 cells, rat liver beta-galactoside alpha-2,6-sialyltransferase cDNA was stably transfected into cells expressing high levels of rHuAChE. rHuAChE produced by the modified cells displayed a significantly higher proportion of fully sialylated glycans as shown by sialic acid incorporation assays, direct measurement of sialic acid, and HPAEC glycan profiling. Genetically modified sialylated rHuAChE exhibited increased circulatory retention (the slow-phase half-life, t12beta, was 130 min, compared with 80 min for the undersialylated enzyme). Interestingly, the same increase in circulatory residence was observed when rHuAChE was subjected to extensive sialylation in vitro. The engineered HEK-293 cells in which the glycosylation machinery was modified might represent a valuable tool for the high level of expression of recombinant glycoproteins whose sialic acid content is important for their function or for pharmacokinetic behaviour.
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