ArticleProceedings of the National Academy of Sciences of the United States of America2012
Synthesis of site-specific antibody-drug conjugates using unnatural amino acids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 259 papers.
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Who cites it
259 citing papers in PubMed, 567 citations in OpenAlex.
- Trial watch: antibody-drug conjugates in cancer therapy.Oncoimmunology · 2026Review
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- Antibody-drug conjugate engineering: from design to efficacy and safety.Signal transduction and targeted therapy · 2026Review
- Multivalent antibody-based conjugates as new tools for tailored modulation of G protein-coupled receptors.British journal of pharmacology · 2026Review
- From Unmet Medical Need to Drug Candidate: A Translational Therapeutic Development Roadmap Illustrated by Dual-Payload Antibody-Drug Conjugates.Biomolecules · 2026Review
- ADC Conjugation Strategies: From Technological Evolution to a Practical Selection Framework.Pharmaceutics · 2026Review
- Orthogonal Conjugation via Endoglycosidase and Microbial Transglutaminase Enables Efficient Synthesis of Dual-Payload Antibody-Drug Conjugates.ACS chemical biology · 2026Article
- Therapeutic peptides and proteins: Status and developments in drug delivery.Journal of controlled release : official journal of the Controlled Release Society · 2026Review
- Unnatural amino acid compounds as potent multi-target inhibitors of aldose reductase, α-glucosidase, and α-amylase: integrated in vitro, SAR, and molecular dynamics insights.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Enabling the synthesis of multi-payload thio-antibody conjugates through the use of pyridazinediones,RSC chemical biology · 2026Article
- Recoding multiple rare codons enables the simultaneous incorporation of up to five distinct noncanonical amino acids.Nature chemistry · 2026Article
- CLL-1: An emerging target for immunotherapy in acute myeloid leukemia.Annals of hematology · 2026Review
- Site-Specific Glycan Conjugation Improves Stability and Efficacy of an Antibody-Drug Conjugates Bearing DXd as a Cytotoxic Payload.ACS omega · 2026Article
- Development and Optimization of an Aminooxy Coupling Reaction to Prepare Multivalent Bioconjugates with a Single Noncanonical Amino Acid.Bioconjugate chemistry · 2026Article
- Efficient Preparation of Homogenous Antibody Conjugates via Glycosite-Specific Transglycosylation Enabled by Readily Available Glycosyl Donors.Angewandte Chemie (International ed. in English) · 2026Article
- Targeting angiogenesis: advances in the design and engineered applications of nanobodies.Frontiers in immunology · 2026Review
- Development of a dendritic cell-targeted vaccine strategy using proximity-induced conjugation.Theranostics · 2026Article
- Nanobody-Based Drug Delivery: Emerging Strategies for Targeted Cancer Therapy.International journal of nanomedicine · 2026Review
- The landscape of antibody production systems: recombinant expression for research, diagnostics and therapy.Frontiers in bioengineering and biotechnology · 2026Review
- Glycan Remodeling Technologies for Enhancing Antibody Function.Advances in experimental medicine and biology · 2026Review
199 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
Antibody-drug conjugates (ADCs) allow selective targeting of cytotoxic drugs to cancer cells presenting tumor-associated surface markers, thereby minimizing systemic toxicity. Traditionally, the drug is conjugated nonselectively to cysteine or lysine residues in the antibody. However, these strategies often lead to heterogeneous products, which make optimization of the biological, physical, and pharmacological properties of an ADC challenging. Here we demonstrate the use of genetically encoded unnatural amino acids with orthogonal chemical reactivity to synthesize homogeneous ADCs with precise control of conjugation site and stoichiometry. p-Acetylphenylalanine was site-specifically incorporated into an anti-Her2 antibody Fab fragment and full-length IgG in Escherichia coli and mammalian cells, respectively. The mutant protein was selectively and efficiently conjugated to an auristatin derivative through a stable oxime linkage. The resulting conjugates demonstrated excellent pharmacokinetics, potent in vitro cytotoxic activity against Her2(+) cancer cells, and complete tumor regression in rodent xenograft treatment models. The synthesis and characterization of homogeneous ADCs with medicinal chemistry-like control over macromolecular structure should facilitate the optimization of ADCs for a host of therapeutic uses.
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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.