Polysialylated insulin: synthesis, characterization and biological activity in vivo

Jain, Sanjay; Hreczuk-Hirst, Dale; McCormack, Brenda; Mital, Malini; Epenetos, Agamemnon A.; Laing, Peter; Gregoriadis, Gregory

doi:10.1016/s0304-4165(03)00116-8

Cited by 115 publications

(67 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In humans, polySia is found on neural cell adhesion molecules (NCAM), where it plays a vital role in brain development (10). Clinical studies with polysialylated insulin and erythropoietin have shown that polySia is a superb alternative to polyethyleneglycol (PEG) in endowing protein drugs with longer circulatory half-lives and reduced immunogenicity (11). Furthermore, chemically polysialylated antitumor mAb fragments (scFvs) have shown significant increase in bioavailability and tumor uptake, suggesting scFvs with polySia are a viable alternative to whole IgGs (12).…”

mentioning

confidence: 99%

Glycoengineering of plants yields glycoproteins with polysialylation and other defined N-glycoforms

Chen

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

mentioning

confidence: 99%

Glycoengineering of plants yields glycoproteins with polysialylation and other defined N-glycoforms

Chen

2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

“…PSA modification of therapeutic proteins is an attractive alternative to PEGylation, given that PSA is biodegradable and nonimmunogenic. PSA has been chemically conjugated to a few clinically relevant therapeutic proteins and was shown to improve their circulating half-life without adversely affecting their function (10,11). Recently, site-specific chemical coupling of PSA was demonstrated on an antitumor single-chain variable region fragment (12), but this requires engineering a terminal Cys, which is not always an option for other therapeutic proteins.…”

mentioning

confidence: 99%

Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes

Lindhout

Iqbal

Willis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

108

View full text Add to dashboard Cite

The posttranslational modification of therapeutic proteins with terminal sialic acids is one means of improving their circulating half-life, thereby improving their efficiency. We have developed a two-step in vitro enzymatic modification of glycoproteins, which has previously only been achieved by chemical means [Gregoriadis G, Jain S, Papaioannou I, Laing P (2005) Int J Pharm 300:125-130). This two-step procedure uses the Campylobacter jejuni Cst-II α2,8-sialyltransferase to provide a primer on N-linked glycans, followed by polysialylation using the Neisseria meningitidis α2,8-polysialyltransferase. Here, we have demonstrated the ability of this system to modify three glycoproteins with varying N-linked glycan compositions: the human therapeutic proteins alpha-1-antitrypsin (A1AT) and factor IX, as well as bovine fetuin. The chain length of the polysialic acid addition was optimized by controlling reaction conditions. After demonstrating the ability of this system to modify a variety of proteins, the effect of polysialylation on the activity and serum half-life of A1AT was examined. The polysialylation of A1AT did not adversely affect its in vitro inhibition activity against human neutrophil elastase. The polysialylation of A1AT resulted in a significantly improved pharmacokinetic profile when the modified proteins were injected into CD-1 mice. Together, these results suggest that polysialylated A1AT may be useful for improved augmentation therapy for patients with a deficiency in this protein and that this modification may be applied to other therapeutic proteins.glycosyltransferase | glycosylation

show abstract

“…for injection into humans in significant amounts for pretreatment against OPs with remarkable reduction of side effects, including immune response (34,38,39).…”

Section: Resultsmentioning

confidence: 99%

“…In additional to PEG, polysialic acids can be used to increase the molecular size of rBChE. These molecules were shown to improve pharmacokinetics of test drugs (33), leaving the drug active after modification (34,35). Unlike other hydrophilic polymers, such as PEG or dextran, polysialic acids are biodegradable, less likely to cause immunogenic response, and their catabolic product (i.e., NeuNAc) is not known to be toxic (36).…”

mentioning

confidence: 99%

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

Ilyushin

Смирнов

Belogurov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

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.organophosphate | N-acetylneuraminic acid | Russian VX | pesticide | mass spectrometry

show abstract

Polysialylated insulin: synthesis, characterization and biological activity in vivo

Cited by 115 publications

References 39 publications

Glycoengineering of plants yields glycoproteins with polysialylation and other defined N-glycoforms

Glycoengineering of plants yields glycoproteins with polysialylation and other defined N-glycoforms

Site-specific enzymatic polysialylation of therapeutic proteins using bacterial enzymes

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

Contact Info

Product

Resources

About