AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies
| Autor: | Kazutaka Shimbo, Yutaka Matsuda, Brian A. Mendelsohn, Yuji Ito, Zahra Khedri, Shikida Natsuki, Kei Yamada |
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| Rok vydání: | 2018 |
| Předmět: |
chemistry.chemical_classification
Immunoconjugates 010405 organic chemistry Ligand binding assay Biomolecule Lysine Chemical biology Peptide General Chemistry General Medicine 010402 general chemistry 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences Amino acid chemistry Covalent bond Humans Surface plasmon resonance Peptides |
| Zdroj: | Angewandte Chemie (International ed. in English). 58(17) |
| ISSN: | 1521-3773 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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