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AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies
Author(s) -
Yamada Kei,
Shikida Natsuki,
Shimbo Kazutaka,
Ito Yuji,
Khedri Zahra,
Matsuda Yutaka,
Mendelsohn Brian A.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201814215
Subject(s) - peptide , chemistry , biomolecule , combinatorial chemistry , surface plasmon resonance , covalent bond , surface modification , lysine , antibody , peptide library , amino acid , small molecule , biochemistry , stereochemistry , peptide sequence , nanotechnology , biology , organic chemistry , immunology , materials science , nanoparticle , gene
The need for atom‐precise biomolecule modification, and particularly the irreversible formation of covalent bonds to specific amino acids in proteins, has become an essential issue in the fields of pharmaceuticals and chemical biology. For example, antibody–drug conjugates (ADCs) are increasingly common entries into the clinical oncology pipeline. Herein, we report a new method of affinity peptide mediated regiodivergent functionalization (AJICAP™) that enables the synthesis of ADCs from native IgG antibodies. We succeeded in introducing thiol functional groups onto three lysine residues in IgGs using Fc affinity peptide reagents without antibody engineering. A cytotoxic molecule was then connected to the newly introduced thiol group, and both a surface plasmon resonance binding assay and in vivo xenograft mouse model results showed that the resulting ADC could selectively target and kill HER2‐positive cells. Our strategy provides a new approach for constructing complex antibody‐derived biomolecules.