Evidence map›Paper›PMID 40244636›Full record

ArticleChembiochem : a European journal of chemical biology2025

A Recognition Tag of Human Origin for Bioorthogonal Generation of Antibody-Drug Conjugates using Microbial Biotin Ligase.

Peter Bitsch, Sebastian Bitsch, Noah Murmann, Ingo Bork, Janine Becker, Harald Kolmar

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Peter BitschClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
Sebastian BitschClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
Noah MurmannClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
Ingo BorkClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
Janine BeckerClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.
Harald KolmarClemens-Schöpf Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Peter-Grünberg-Str. 4, 64287, Darmstadt, Germany.ORCID https://orcid.org/0000-0002-8210-1993

Funding

ChimeraX -- Next Generation Visualization and Analysis Software for Multiscale ModelingR01GM129325 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2018 to 2025
$5.2M
NIGMS NIH HHS R01 GM129325NIH HHS R01-GM129325
6 · The paper itself

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.

Indexed as

Carbon-Nitrogen LigasesImmunoconjugatesTrastuzumabAzidesBiotinCell Line, TumorHumansAzidesBiotinCarbon-Nitrogen LigasesImmunoconjugatesTrastuzumabantibody‐drug conjugatesbioconjugationbiotin ligaseMMAEp67

Identifiers

PMID40244636
PMCPMC12117412

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.