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Related Concept Videos

T Cell Activation and Clonal Selection01:22

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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
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Development of tCAP(N3): Affinity Peptide-Aided, pH-Triggered Strategy for Site-Specific Native IgG Modification.

Hiroko Kawakami1,2, Abdur Rafique1, Shugo Tsuda2

  • 1Graduate School of Science and Engineering, Kagoshima University, Kagoshima, Japan.

Chemistry (Weinheim an Der Bergstrasse, Germany)
|December 24, 2025
PubMed
Summary

We developed traceless chemical conjugation (tCAP(N3)), a novel method for modifying antibodies with affinity peptides. This technique enables site-selective peptide transfer, creating stable antibody conjugates that retain biological function.

Keywords:
antibodyantibody drug ratiocancerpayloadstoxic effects

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Area of Science:

  • Bioconjugation Chemistry
  • Antibody Engineering
  • Chemical Biology

Background:

  • Direct modification of native antibodies with affinity peptides is challenging due to peptide interference with antibody function.
  • Existing methods often result in blocked antibody-receptor interactions, limiting their therapeutic potential.

Purpose of the Study:

  • To develop a novel, traceless chemical conjugation method for site-selective antibody modification.
  • To create stable antibody conjugates with preserved biological activity using an affinity peptide.

Main Methods:

  • Development of traceless chemical conjugation (tCAP(N3)) using an active ester precursor for spontaneous activation.
  • Site-selective transfer of an azide-containing peptide onto Lys248 of native IgG.
  • Further modification of azidated IgG with DBCO compounds for conjugation.

Main Results:

  • tCAP(N3) allows for stable storage and spontaneous activation under neutral conditions.
  • Site-selective azidation of IgG at Lys248 was achieved, yielding divalently azidated IgG.
  • The resulting antibody conjugates demonstrated retained Fc receptor binding and antigen recognition comparable to unmodified IgG.

Conclusions:

  • tCAP(N3) offers a robust and traceless method for antibody modification with affinity peptides.
  • This approach yields antibody conjugates with preserved essential biological functions.
  • The developed method holds promise for advancing antibody-based therapeutics and diagnostics.