ArticleProceedings of the National Academy of Sciences of the United States of America2000
Directed evolution of antibody fragments with monovalent femtomolar antigen-binding affinity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers.
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Who cites it
232 citing papers in PubMed.
- Prediction of antibody non-specificity using protein language models and biophysical parameters.mAbs · 2026Article
- DOTAM-TCB: Universal Small Molecule-guided Hapten- and T Cell-bispecific Antibodies for Cancer Immunotherapy.Antibody therapeutics · 2026Article
- Single-molecule peptide sequencing through reverse translation of peptides into DNA.Nature biotechnology · 2026Article
- Simultaneous Affinity Maturation and Liability Removal from Antibodies.Methods in molecular biology (Clifton, N.J.) · 2026Article
- High-Efficiency Transformation of Integrative Libraries Under Zeocin Selection in Pichia pastoris.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Decoding protein binding plasticity via integrated deep ribosome display and deep learning.Communications biology · 2025Article
- A review of targeted drug delivery with antibody-drug complexes.The Journal of pharmacology and experimental therapeutics · 2025Review
- Engineering HIV antibodies with enhanced breadth and potency of neutralization through multistate affinity maturation.bioRxiv : the preprint server for biology · 2025Article
- Ultra-efficient Integration of Gene Libraries onto Yeast Cytosolic Plasmids.ACS synthetic biology · 2025Article
- Retrospective SARS-CoV-2 human antibody development trajectories are largely sparse and permissive.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Fluorescein-based SynNotch adaptors for regulating gene expression responses to diverse extracellular and matrix-based cues.Nature communications · 2025Article
- Directed evolution of drug-like Aβ conformation-specific antibodies.Frontiers in immunology · 2025Article
- Trade-off between the antiviral and vaccinal effects of antibody therapy in the humoral response to HIV.Journal of the Royal Society, Interface · 2024Article
- Physical extraction of antigen and information.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Addressing epistasis in the design of protein function.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Toxic Peptides from the Mexican ScorpionToxins · 2024Article
- Cancer therapy with antibodies.Nature reviews. Cancer · 2024Review
- Development of a new affinity maturation protocol for the construction of an internalizing anti-nucleolin antibody library.Scientific reports · 2024Article
- Mechanical force determines chimeric antigen receptor microclustering and signaling.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Identification of a potent PCNA-p15-interaction inhibitor by autodisplay-based peptide library screening.Microbial biotechnology · 2024Article
172 more citing papers are in PubMed but not listed here.
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Funding
Abstract
Single-chain antibody mutants have been evolved in vitro with antigen-binding equilibrium dissociation constant K(d) = 48 fM and slower dissociation kinetics (half-time > 5 days) than those for the streptavidin-biotin complex. These mutants possess the highest monovalent ligand-binding affinity yet reported for an engineered protein by over two orders of magnitude. Optimal kinetic screening of randomly mutagenized libraries of 10(5)-10(7) yeast surface-displayed antibodies enabled a >1,000-fold decrease in the rate of dissociation after four cycles of affinity mutagenesis and screening. The consensus mutations are generally nonconservative by comparison with naturally occurring mouse Fv sequences and with residues that do not contact the fluorescein antigen in the wild-type complex. The existence of these mutants demonstrates that the antibody Fv architecture is not intrinsically responsible for an antigen-binding affinity ceiling during in vivo affinity maturation.
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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.