ArticleACS chemical biology2016
Stabilizing the CH2 Domain of an Antibody by Engineering in an Enhanced Aromatic Sequon.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
- Fc engineering of a fully humanized anti-CD147 monoclonal antibody enhances ADCC against T-cell acute lymphoblastic leukemia and T-lymphoblastic lymphoma.Scientific reports · 2026Article
- Comparative Analysis of Glycan Composition in Therapeutic Antibodies via Glycan Profiling and Intact Mass Analysis.Molecules (Basel, Switzerland) · 2025Article
- Glycosylated Foot-And-Mouth Disease Virus-Like Particles Produced in Pichia Pastoris Enhance Stability and Immunogenicity.Microbial biotechnology · 2025Article
- Protein Glycosylation Patterns Shaped By the IRE1-XBP1s Arm of the Unfolded Protein Response.Israel journal of chemistry · 2024Article
- Systematic Preparation of a 66-IgG Library with Symmetric and Asymmetric Homogeneous Glycans and Their Functional Evaluation.Journal of the American Chemical Society · 2024Article
- Viscosity Prediction of High-Concentration Antibody Solutions with Atomistic Simulations.Journal of chemical information and modeling · 2023Article
- Site-Specific Antibody Conjugation Using Modified BisectedBioconjugate chemistry · 2023Article
- Decreasing hydrophobicity or shielding hydrophobic areas of CH2 attenuates low pH-induced IgG4 aggregation.Frontiers in bioengineering and biotechnology · 2023Article
- Chemico-Pharmacological Screening of the Methanol Extract ofMolecules (Basel, Switzerland) · 2022Article
- Impact of Drug Conjugation on Thermal and Metabolic Stabilities of Aglycosylated andBioconjugate chemistry · 2022Article
- Article
- Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?Pathogens (Basel, Switzerland) · 2021Article
- Glycoengineering Chinese hamster ovary cells: a short history.Biochemical Society transactions · 2021Review
- Glycan-protein interactions determine kinetics ofRSC chemical biology · 2021Article
- Highly sensitive HPLC analysis and biophysical characterization of N-glycans of IgG-Fc domain in comparison between CHO and 293 cells using FcγRIIIa ligand.Biotechnology progress · 2020Article
- A synopsis of recent developments defining how N-glycosylation impacts immunoglobulin G structure and function.Glycobiology · 2020Review
- Comprehensive elucidation of the structural and functional roles of engineered disulfide bonds in antibody Fc fragment.The Journal of biological chemistry · 2018Article
- An oligosaccharyltransferase from Leishmania major increases the N-glycan occupancy on recombinant glycoproteins produced in Nicotiana benthamiana.Plant biotechnology journal · 2018Article
- Heat denaturation of the antibody, a multi-domain protein.Biophysical reviews · 2018Review
- Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Monoclonal antibodies (mAbs) exhibiting highly selective binding to a protein target constitute a large and growing proportion of the therapeutics market. Aggregation of mAbs results in the loss of their therapeutic efficacy and can result in deleterious immune responses. The CH2 domain comprising part of the Fc portion of Immunoglobulin G (IgG) is typically the least stable domain in IgG-type antibodies and therefore influences their aggregation propensity. We stabilized the CH2 domain by engineering an enhanced aromatic sequon (EAS) into the N-glycosylated C'E loop and observed a 4.8 °C increase in the melting temperature of the purified IgG1 Fc fragment. This EAS-stabilized CH2 domain also conferred enhanced stability against thermal and low pH induced aggregation in the context of a full-length monoclonal IgG1 antibody. The crystal structure of the EAS-stabilized (Q295F/Y296A) IgG1 Fc fragment confirms the design principle, i.e., the importance of the GlcNAc1•F295 interaction, and surprisingly reveals that the core fucose attached to GlcNAc1 also engages in an interaction with F295. Inhibition of core fucosylation confirms the contribution of the fucose-Phe interaction to the stabilization. The Q295F/Y296A mutations also modulate the binding affinity of the full-length antibody to Fc receptors by decreasing the binding to low affinity Fc gamma receptors (FcγRIIa, FcγRIIIa, and FcγRIIIb), while maintaining wild-type binding affinity to FcRn and FcγRI. Our results demonstrate that engineering an EAS into the N-glycosylated reverse turn on the C'E loop leads to stabilizing N-glycan-protein interactions in antibodies and that this modification modulates antibody-Fc receptor binding.
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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.