Protein PEGylation, basic science and biological applications

Veronese, Francesco M.; Mero, Anna; Pasut, Gianfranco

doi:10.1007/978-3-7643-8679-5_2

Cited by 82 publications

(96 citation statements)

References 94 publications

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“…As discussed by many researchers PEGylation is a quite promising method for drug delivery [1][2][3][4]. However, the PEGylation reaction is so product Table 1.…”

Section: Discussionmentioning

confidence: 99%

“…Although various technologies have been extensively studied as drug delivery systems, PEGylation, the covalent attachment of polyethylene glycol (PEG) chains to protein, is quite attractive for development of protein or peptide drugs [1][2][3][4]. PEGylation permits prolonged half-life and reduced side effects [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…PEGylation permits prolonged half-life and reduced side effects [1][2][3][4]. Several PEGylated protein drugs such as PEGylated interferons are already on the market, and others are undergoing clinical trials [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

“…However, as the PEGylation reaction is not completely understood, it is not easy to tune or optimize the reaction process [5]. The yield is often quite low [4,5]. The reaction mixture contains unreacted native protein and various different forms of PEGylated protein, from which the desired PEGylated protein must be highly purified.…”

Section: Introductionmentioning

confidence: 99%

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Interaction mechanism of mono‐PEGylated proteins in electrostatic interaction chromatography

Abe

Akbarzaderaleh

Hamachi

et al. 2010

Biotechnology Journal

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The retention and binding mechanisms in electrostatic interaction-based chromatography (ion-exchange chromatography) of PEGylated proteins (covalent attachment of polyethylene glycol chains to protein) were investigated using our previously developed model. Lysozyme and bovine serum albumin were chosen as model proteins. The retention volume of PEGylated proteins shifted to lower elution volumes with increasing PEG molecular weight compared with the non-modified (native) protein retention volume. However, PEGylation did not affect the number of binding sites appreciably. The enzyme activity of PEGylated lysozyme measured with a standard insoluble substrate in suspension decreased considerably, whereas the activity with a soluble small-molecule substrate did not drop significantly. These findings indicate that when a protein is mono-PEGylated, the binding site is not affected and the elution volume reduces due to the steric hindrance between PEGylated protein and ion-exchange ligand.

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“…As discussed by many researchers PEGylation is a quite promising method for drug delivery [1][2][3][4]. However, the PEGylation reaction is so product Table 1.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction mechanism of mono‐PEGylated proteins in electrostatic interaction chromatography

Abe

Akbarzaderaleh

Hamachi

et al. 2010

Biotechnology Journal

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“…For a description of PEGylation and PEGylation examples more detailed than in this short chapter, the reader might refer to the original research papers, to the numerous reviews on the topic or to a recently edited book on PEGylation [ 11 ] .…”

Section: Introductionmentioning

confidence: 99%

Protein PEGylation

Veronese

Pasut

2011

Long Acting Injections and Implants

Self Cite

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The covalent linking of poly(ethylene glycol) (PEG) has become the leading approach to improving the therapeutic effi cacy of proteins. This highly hydrophilic synthetic polymer possesses unique properties that allowed PEG to emerge as the best candidate for protein modifi cation. Beside the proven success of PEG conjugates already on the market, it should be noted that other derivatives are presently under advanced clinical trials. The increased half-life of the conjugates is probably the main reason for performing PEGylation. In addition, the possibility to greatly reduce the immunogenicity of a given protein is also a strong and determinant incentive. This last advantage offers the possibility to safely use, in the clinic, heterologous proteins that otherwise might trigger dramatic immunogenic responses or even anaphylactic reactions. This chapter introduces the reader to PEGylation strategies showing in detail its potential and the achievements obtained in the recent years. Furthermore, the future perspectives of the technique are also discussed.

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Protein Engineering Strategies for Improved Pharmacokinetics

Rondon

Mahri

Morales-Yánez

et al. 2021

Adv Funct Materials

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Protein therapeutics have gained momentum in recent years and become a pillar in treating many diseases and the only choice in several ailments. Protein therapeutics are highly specific, tunable, and less toxic than conventional small drug molecules. However, reaping the full benefits of therapeutic proteins in the clinics is often hindered by issues of immunogenicity and short half-life due essentially to fast renal clearance and enzymatic degradation. Advances in polymer chemistry and protein engineering allowed overcoming some of these limitations. Strategies to prolong the half-life of proteins rely on increasing their size and stability and/or fusing them to endogenous proteins (albumin, Fc fragment of antibody) to hijack physiological pathways involved in protein recycling. On the downside, these modifications might alter therapeutic proteins structure and function. Therefore, a compromise between half-life and activity is sought. This review covers half-life extension strategies using natural and synthetic polymers as well as fusion to other proteins and sheds light on genetic engineering strategies and chemical and enzymatic reactions to achieve this goal. Promising strategies and successful applications in the clinics are highlighted. DOI: . /adfm.functions that cannot be mimicked by simple chemical compounds. Since the action of proteins is highly specific, they barely interfere with normal biological processes and cause less adverse events. Protein therapeutics are frequently derived from proteins naturally produced by the body. These agents are therefore often well tolerated and poorly immunogenic. However, proteins also suffer from significant limitations. Proteins with a molecular weight below the threshold for kidney filtration ( kDa, the size of human serum albumin) are cleared from the systemic circulation within a day. Many proteins are even cleared within a few hours or a few minutes when metabolism contributes to elimination. Therefore, therapeutic proteins need to be injected to patients several times a week (e.g., erythropoietin) or even several times a day (e.g., glucagon-like peptide-or GLP-), resulting in peaks and valleys in plasma concentrations with the alternate risks of systemic side effects and suboptimal therapeutic concentrations. Moreover, frequent administration of medication causes patient discomfort and reduces quality of life. A second limitation of proteins lies in protein immunogenicity. Foreign proteins from prokaryotes or animals might present interesting therapeutic properties in humans. However, intrinsic immunogenicity of nonhuman proteins hampers their therapeutic use in the clinic because specific antibodies generated against the foreign protein neutralize its activity and result in a loss of therapeutic efficacy over time. The unwanted immune response might even cause more serious general immune effects such as anaphylaxis.Over the last three decades, protein engineering has largely demonstrated that it can provide solutions to the limitations of natural proteins. B...

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Protein PEGylation, basic science and biological applications

Cited by 82 publications

References 94 publications

Interaction mechanism of mono‐PEGylated proteins in electrostatic interaction chromatography

Interaction mechanism of mono‐PEGylated proteins in electrostatic interaction chromatography

Protein PEGylation

Protein Engineering Strategies for Improved Pharmacokinetics

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