A PEGylation Technology of L-Asparaginase with Monomethoxy Polyethylene Glycol-Propionaldehyde

Wang, Bochu; Cao, Yang; Chi, Shaoping; Lou, Deshuai

doi:10.1515/znc-2012-5-611

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…Interestingly, the immunogenicity of PEGylated TPPs may be reduced due to steric hindrance caused by PEG, which can impede immune recognition (Harris et al, 2001;Shi et al, 2022). For instance, PEGylation of asparaginase could eliminate its antigenicity (Abuchowski et al, 1977;Duval et al, 2002;Molineux, 2003;Wang et al, 2012).…”

Section: Biological Properties Of Peg and Its Derivativesmentioning

confidence: 99%

“…However, due to short half-life and antigenicity, L-asparaginase induces severe allergic reactions (Chung, 2010). PEGylated L-asparaginase has the ability to shield antigenic epitopes, reduce immunogenicity, prolong plasma retention time, and decrease proteolysis and renal excretion (Duval et al, 2002;Wang et al, 2012;Molineux, 2023). Clinical trials of PEGylated L-asparaginase began in 1984 and it was found to be safe for patients who had previously experienced allergic reactions to E. coli or Erwinia L-asparaginase (Graham, 2003).…”

Section: Pegylated Asparaginasementioning

confidence: 99%

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Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

Li,

Tian

et al. 2024

Front. Pharmacol.

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With the rapid advancement of genetic and protein engineering, proteins and peptides have emerged as promising drug molecules for therapeutic applications. Consequently, there has been a growing interest in the field of chemical modification technology to address challenges associated with their clinical use, including rapid clearance from circulation, immunogenicity, physical and chemical instabilities (such as aggregation, adsorption, deamination, clipping, oxidation, etc.), and enzymatic degradation. Polyethylene glycol (PEG) modification offers an effective solution to these issues due to its favorable properties. This review presents recent progress in the development and application of PEGylated therapeutic proteins and peptides (TPPs). For this purpose, firstly, the physical and chemical properties as well as classification of PEG and its derivatives are described. Subsequently, a detailed summary is provided on the main sites of PEGylated TPPs and the factors that influence their PEGylation. Furthermore, notable instances of PEG-modified TPPs (including antimicrobial peptides (AMPs), interferon, asparaginase and antibodies) are highlighted. Finally, we propose the chemical modification of TPPs with PEG, followed by an analysis of the current development status and future prospects of PEGylated TPPs. This work provides a comprehensive literature review in this promising field while facilitating researchers in utilizing PEG polymers to modify TPPs for disease treatment.

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Section: Biological Properties Of Peg and Its Derivativesmentioning

confidence: 99%

Section: Pegylated Asparaginasementioning

confidence: 99%

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

Li,

Tian

et al. 2024

Front. Pharmacol.

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A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models

Van Trimpont,

Schalk,

Hofkens

et al. 2025

Cancer Letters

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Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

Hang

Kang

Song

et al. 2017

Sci Rep

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Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line. The EC50 dose-response curves for GCSF, GCSF-Fc and PEG-GCSF were 37 ± 12 pM, 75 ± 13.5 pM and 46 ± 5.5 pM, respectively. When the proteins were injected into neutropenic rats, the group injected with PEG-GCSF showed the highest and fastest recovery of neutrophils, followed by GCSF-Fc and GCSF. ELISA assay revealed the PEG-GCSF had the longest plasma circulation (>72 h), followed by GCSF-Fc (>48 h) and GCSF (~24 h), which is consistent with the in vivo activities of the proteins. In summary, the GCSF-Fc purified from E. coli was not as efficient as PEG-GCSF in treating neutropenic rats.

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A PEGylation Technology of L-Asparaginase with Monomethoxy Polyethylene Glycol-Propionaldehyde

Cited by 6 publications

References 20 publications

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

Research progress on the PEGylation of therapeutic proteins and peptides (TPPs)

A human-like glutaminase-free asparaginase is highly efficacious in ASNSlow leukemia and solid cancer mouse xenograft models

Granulocyte colony-stimulating factor (GCSF) fused with Fc Domain produced from E. coli is less effective than Polyethylene Glycol-conjugated GCSF

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