ArticleThe Journal of biological chemistry2012
Elucidation of acid-induced unfolding and aggregation of human immunoglobulin IgG1 and IgG2 Fc.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed.
- Effect of ADCC-enhancing mutations on N-glycan profiles of human IgG1 antibodies.The Biochemical journal · 2026Article
- Optimisation of a Caprylic Acid-Based Protocol for IgG Purification from Baboon (Methods and protocols · 2026Article
- Understanding the Role of Polyols and Sugars in Reducing Aggregation in IgGPharmaceuticals (Basel, Switzerland) · 2025Article
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Linker minimization and characterization of Fc-fused interleukin-17A for increased in vivo half-life.Protein engineering, design & selection : PEDS · 2025Article
- Analysis of the Structure of 14 Therapeutic Antibodies Using Circular Dichroism Spectroscopy.Analytical chemistry · 2024Article
- Enhancing thermal stability in the CHProtein science : a publication of the Protein Society · 2023Article
- Neuronal binding by antibodies can be influenced by low pH stress during the isolation procedure.Journal of immunological methods · 2023Article
- Rapid purification of rabbit immunoglobulins using a single-step, negative-selection chromatography.Protein expression and purification · 2023Article
- Getting Smaller by Denaturation: Acid-Induced Compaction of Antibodies.The journal of physical chemistry letters · 2023Article
- Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.Frontiers in bioengineering and biotechnology · 2023Article
- Metabolic Vulnerabilities in Multiple Myeloma.Cancers · 2022Review
- Tumor acidity: From hallmark of cancer to target of treatment.Frontiers in oncology · 2022Review
- Aggregation of protein therapeutics enhances their immunogenicity: causes and mitigation strategies.RSC chemical biology · 2021Review
- Requirement of Fc-Fc Gamma Receptor Interaction for Antibody-Based Protection against Emerging Virus Infections.Viruses · 2021Review
- Shelf-Life Extension of Fc-Fused Single Chain Fragment Variable Antibodies by Lyophilization.Frontiers in cellular and infection microbiology · 2021Article
- Engineering a human IgG2 antibody stable at low pH.Protein science : a publication of the Protein Society · 2020Article
- In situ neutron scattering of antibody adsorption during protein A chromatography.Journal of chromatography. A · 2020Article
- Modelling of pH-dependence to develop a strategy for stabilising mAbs at acidic steps in production.Computational and structural biotechnology journal · 2020Review
- Purification of Antibodies From Human Milk and Infant Digestates for Viral Inhibition Assays.Frontiers in nutrition · 2020Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the underlying mechanisms of Fc aggregation is an important prerequisite for developing stable and efficacious antibody-based therapeutics. In our study, high resolution two-dimensional nuclear magnetic resonance (NMR) was employed to probe structural changes in the IgG1 Fc. A series of (1)H-(15)N heteronuclear single-quantum correlation NMR spectra were collected between pH 2.5 and 4.7 to assess whether unfolding of C(H)2 domains precedes that of C(H)3 domains. The same pH range was subsequently screened in Fc aggregation experiments that utilized molecules of IgG1 and IgG2 subclasses with varying levels of C(H)2 glycosylation. In addition, differential scanning calorimetry data were collected over a pH range of 3-7 to assess changes in C(H)2 and C(H)3 thermostability. As a result, compelling evidence was gathered that emphasizes the importance of C(H)2 stability in determining the rate and extent of Fc aggregation. In particular, we found that Fc domains of the IgG1 subclass have a lower propensity to aggregate compared with those of the IgG2 subclass. Our data for glycosylated, partially deglycosylated, and fully deglycosylated molecules further revealed the criticality of C(H)2 glycans in modulating Fc aggregation. These findings provide important insights into the stability of Fc-based therapeutics and promote better understanding of their acid-induced aggregation process.
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Registered trials
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.