ArticleBiotechnology journal2014
Construction of pH-sensitive Her2-binding IgG1-Fc by directed evolution.
Article in Biotechnology journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Engineering and Adapting Disulfide-Containing Proteins to Enable Intracellular Functionality.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Article
- Deep sequencing combined with high-throughput screening enables efficient development of a pH-dependent high-affinity binding domain targeting HER3.Protein science : a publication of the Protein Society · 2025Article
- Serum immunoglobulin or albumin binding single-domain antibodies that enable tailored half-life extension of biologics in multiple animal species.Frontiers in immunology · 2024Article
- Conditionally Active, pH-Sensitive Immunoregulatory Antibodies Targeting VISTA and CTLA-4 Lead an Emerging Class of Cancer Therapeutics.Antibodies (Basel, Switzerland) · 2023Review
- Selection of High-Affinity Heterodimeric Antigen-Binding Fc Fragments from a Large Yeast Display Library.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Yeast Display Guided Selection of pH-Dependent Binders.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A stepwise mutagenesis approach using histidine and acidic amino acid to engineer highly pH-dependent protein switches.3 Biotech · 2022Article
- The Masking Game: Design of Activatable Antibodies and Mimetics for Selective Therapeutics and Cell Control.ACS central science · 2021Review
- Beyond antibody engineering: directed evolution of alternative binding scaffolds and enzymes using yeast surface display.Microbial cell factories · 2018Review
- A novel one-step approach for the construction of yeast surface display Fab antibody libraries.Microbial cell factories · 2018Article
- Article
- Engineering a pH responsive pore forming protein.Scientific reports · 2017Article
- Fc Engineering for Developing Therapeutic Bispecific Antibodies and Novel Scaffolds.Frontiers in immunology · 2017Review
- Isolation of a pH-Sensitive IgNAR Variable Domain from a Yeast-Displayed, Histidine-Doped Master Library.Marine biotechnology (New York, N.Y.) · 2016Article
- Engineered IgG1-Fc--one fragment to bind them all.Immunological reviews · 2016Review
- Article
- Engineering an Anti-Transferrin Receptor ScFv for pH-Sensitive Binding Leads to Increased Intracellular Accumulation.PloS one · 2015Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
For most therapeutic proteins, a long serum half-life is desired. Studies have shown that decreased antigen binding at acidic pH can increase serum half-life. In this study, we aimed to investigate whether pH-dependent binding sites can be introduced into antigen binding crystallizable fragments of immunoglobulin G1 (Fcab). The C-terminal structural loops of an Fcab were engineered for reduced binding to the extracellular domain of human epidermal growth factor receptor 2 (Her2-ECD) at pH 6 compared to pH 7.4. A yeast-displayed Fcab-library was alternately selected for binding at pH 7.4 and non-binding at pH 6.0. Selected Fcab variants showed clear pH-dependent binding to soluble Her2-ECD (decrease in affinity at pH 6.0 compared to pH 7.4) when displayed on yeast. Additionally, some solubly expressed variants exhibited pH-dependent interactions with Her2-positive cells whereas their conformational and thermal stability was pH-independent. Interestingly, two of the three Fcabs did not contain a single histidine mutation but all of them contained variations next to histidines that already occurred in loops of the lead Fcab. The study demonstrates that yeast surface display is a valuable tool for directed evolution of pH-dependent binding sites in proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.