ArticleChembiochem : a European journal of chemical biology2025
A Recognition Tag of Human Origin for Bioorthogonal Generation of Antibody-Drug Conjugates using Microbial Biotin Ligase.
Article in Chembiochem : a European journal of chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- The evolving landscape of enzymatic technologies for precision synthesis of antibody-drug conjugates.Antibody therapeutics · 2026Review
- Exploiting Selective Position Labeling to Unveil the Hidden Complexity of Terminomics.Molecules (Basel, Switzerland) · 2026Review
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Authors and funding
6 authors.
Funding
Abstract
The use of enzymes, such as microbial transglutaminase, lipoate protein ligase A, or sortase A, for the generation of antibody-drug conjugates has proven to be a powerful tool for the site-specific payload conjugation to tumor-specific antibodies. Herein, the extension of this enzymatic toolbox by Pyrococcus horikoshii biotin ligase is reported. To this end, the therapeutic antibody trastuzumab is equipped with p67, the 67 amino acid carboxyl-terminal domain of human propionyl-CoA carboxylase α subunit, at the C-terminus of either the light or heavy chain (Trz-LC:p67 and Trz-HC:p67). Upon incubation with PhBL, the azide-bearing linker desthiobiotin azide is site-specifically coupled to the p67 domains at the antibody. Subsequent strain-promoted azide-alkyne cycloaddition with DBCO-AF488 and DBCO-Val-Cit-PAB-MMAE yielded conjugates near to full conversion. In cellular assays, these constructs exhibit single-digit nanomolar EC50 values in cellular proliferation assays on SK-BR-3 and A431 cells, where no significant difference in the performance between the two variants Trz-LC:p67-MMAE and Trz-HC:p67-MMAE is observed. On high Fc-γIIIa receptor expressing Jurkat cells, Trz-HC:p67-MMAE exhibits higher potency than Trz-LC:p67-MMAE, indicating an Fc-blocking effect of p67 when fused to the light chain.
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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 Socratic graph.