ArticleProtein science : a publication of the Protein Society2006
Modulation of protein aggregation by polyethylene glycol conjugation: GCSF as a case study.
Article in Protein science : a publication of the Protein Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 132 citations in OpenAlex.
- Trial
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- A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.Pharmaceutics · 2023Review
- Nanomedicine strategies for central nervous system (CNS) diseases.Frontiers in biomaterials science · 2023Article
- Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.Pharmaceutics · 2022Review
- Atomic-Scale View of Protein-PEG Interactions that Redirect the Thermal Unfolding Pathway of PEGylated Human Galectin-3.Angewandte Chemie (International ed. in English) · 2022Article
- Impact of the PEG length and PEGylation site on the structural, thermodynamic, thermal, and proteolytic stability of mono-PEGylated alpha-1 antitrypsin.Protein science : a publication of the Protein Society · 2022Article
- The ELISA Detectability and Potency of Pegfilgrastim Decrease in Physiological Conditions: Key Roles for Aggregation and Individual Variability.Scientific reports · 2020Article
- Enhancing bioactivity, physicochemical, and pharmacokinetic properties of a nano-sized, anti-VEGFR2 Adnectin, through PASylation technology.Scientific reports · 2019Article
- Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools.Biochemistry · 2017Article
- An anti-TNF-α antibody mimetic to treat ocular inflammation.Scientific reports · 2016Article
- Single-Step Purification of Ovalbumin from Egg White Using Aqueous Biphasic Systems.Process biochemistry (Barking, London, England) · 2016Article
- Fully Synthetic Granulocyte Colony-Stimulating Factor Enabled by Isonitrile-Mediated Coupling of Large, Side-Chain-Unprotected Peptides.Journal of the American Chemical Society · 2015Article
- Nonspecific shielding of unfavorable electrostatic intramolecular interactions in the erythropoietin native-state increase conformational stability and limit non-native aggregation.Protein science : a publication of the Protein Society · 2015Article
- Article
- PEGylation of concanavalin A to improve its stability for an in vivo glucose sensing assay.Analytical chemistry · 2014Article
- Basics and recent advances in peptide and protein drug delivery.Therapeutic delivery · 2013Article
- PEGylated interferon beta-1a in the treatment of multiple sclerosis - an update.Biologics : targets & therapy · 2013Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polyethylene glycol (PEG) conjugation to proteins has emerged as an important technology to produce drug molecules with sustained duration in the body. However, the implications of PEG conjugation to protein aggregation have not been well understood. In this study, conducted under physiological pH and temperature, N-terminal attachment of a 20 kDa PEG moiety to GCSF had the ability to (1) prevent protein precipitation by rendering the aggregates soluble, and (2) slow the rate of aggregation relative to GCSF. Our data suggest that PEG-GCSF solubility was mediated by favorable solvation of water molecules around the PEG group. PEG-GCSF appeared to aggregate on the same pathway as that of GCSF, as evidenced by (a) almost identical secondary structural transitions accompanying aggregation, (b) almost identical covalent character in the aggregates, and (c) the ability of PEG-GCSF to rescue GCSF precipitation. To understand the role of PEG length, the aggregation properties of free GCSF were compared to 5kPEG-GCSF and 20kPEG-GCSF. It was observed that even 5kPEG-GCSF avoided precipitation by forming soluble aggregates, and the stability toward aggregation was vastly improved compared to GCSF, but only marginally less stable than the 20kPEG-GCSF. Biological activity measurements demonstrated that both 5kPEG-GCSF and 20kPEG-GCSF retained greater activity after incubation at physiological conditions than free GCSF, consistent with the stability measurements. The data is most compatible with a model where PEG conjugation preserves the mechanism underlying protein aggregation in GCSF, steric hindrance by PEG influences aggregation rate, while aqueous solubility is mediated by polar PEG groups on the aggregate surface.
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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.