ArticleProceedings of the National Academy of Sciences of the United States of America2014
SpyLigase peptide-peptide ligation polymerizes affibodies to enhance magnetic cancer cell capture.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 173 citations in OpenAlex.
- The evolving landscape of enzymatic technologies for precision synthesis of antibody-drug conjugates.Antibody therapeutics · 2026Review
- Enhancing the sensitivity of nanobodies through covalent and non-covalent polymerization.RSC advances · 2026Article
- Protein nanocages: A new frontier in mucosal vaccine delivery and immune activation.Human vaccines & immunotherapeutics · 2025Review
- Synthesis of Chirally Chimeric Protein Nanoparticle Vaccines via Mirror-Image Spy Chemistry.Angewandte Chemie (International ed. in English) · 2025Article
- Bioengineering Outer-Membrane Vesicles for Vaccine Development: Strategies, Advances, and Perspectives.Vaccines · 2025Review
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- Bridging Nature and Engineering: Protein-Derived Materials for Bio-Inspired Applications.Biomimetics (Basel, Switzerland) · 2024Review
- Irreversible light-activated SpyLigation mediates split-protein assembly in 4D.Nature protocols · 2024Review
- SpSrtA-Catalyzed Isopeptide Ligation on Lysine Residues.Microorganisms · 2024Article
- Research progress of cell membrane biomimetic nanoparticles for circulating tumor cells.Frontiers in oncology · 2024Review
- Design and Evolution of Enhanced Peptide-Peptide Ligation for Modular Transglutaminase Assembly.Bioconjugate chemistry · 2023Article
- Dual-Warhead Conjugate Based on Fibroblast Growth Factor 2 Dimer Loaded with α-Amanitin and Monomethyl Auristatin E Exhibits Superior Cytotoxicity towards Cancer Cells Overproducing Fibroblast Growth Factor Receptor 1.International journal of molecular sciences · 2023Article
- Spatiotemporal functional assembly of split protein pairs through a light-activated SpyLigation.Nature chemistry · 2023Article
- Antibody drug conjugates as targeted cancer therapy: past development, present challenges and future opportunities.Archives of pharmacal research · 2023Review
- Microbial Synthesis of High-Molecular-Weight, Highly Repetitive Protein Polymers.International journal of molecular sciences · 2023Review
- Ferritin nanocages as efficient nanocarriers and promising platforms for COVID-19 and other vaccines development.Biochimica et biophysica acta. General subjects · 2023Review
- Display of multiple proteins on engineered canine parvovirus-like particles expressed in cultured silkworm cells and silkworm larvae.Frontiers in bioengineering and biotechnology · 2023Article
- Recent advances in developing active targeting and multi-functional drug delivery systems via bioorthogonal chemistry.Signal transduction and targeted therapy · 2022Review
- Peptide/protein-based macrocycles: from biological synthesis to biomedical applications.RSC chemical biology · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Individual proteins can now often be modified with atomic precision, but there are still major obstacles to connecting proteins into larger assemblies. To direct protein assembly, ideally, peptide tags would be used, providing the minimal perturbation to protein function. However, binding to peptides is generally weak, so assemblies are unstable over time and disassemble with force or harsh conditions. We have recently developed an irreversible protein-peptide interaction (SpyTag/SpyCatcher), based on a protein domain from Streptococcus pyogenes, that locks itself together via spontaneous isopeptide bond formation. Here we develop irreversible peptide-peptide interaction, through redesign of this domain and genetic dissection into three parts: a protein domain termed SpyLigase, which now ligates two peptide tags to each other. All components expressed efficiently in Escherichia coli and peptide tags were reactive at the N terminus, at the C terminus, or at internal sites. Peptide-peptide ligation enabled covalent and site-specific polymerization of affibodies or antibodies against the tumor markers epidermal growth factor receptor (EGFR) and HER2. Magnetic capture of circulating tumor cells (CTCs) is one of the most promising approaches to improve cancer prognosis and management, but CTC capture is limited by inefficient recovery of cells expressing low levels of tumor antigen. SpyLigase-assembled protein polymers made possible the isolation of cancerous cells expressing lower levels of tumor antigen and should have general application in enhancing molecular capture.
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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.