肽
化学
生物分子
表面等离子共振
组合化学
共价键
表面改性
抗体
赖氨酸
肽库
氨基酸
硫醇
结合
生物化学
立体化学
肽序列
纳米技术
生物
有机化学
免疫学
纳米颗粒
材料科学
物理化学
数学分析
基因
数学
作者
Kei Yamada,Natsuki Shikida,Kazutaka Shimbo,Yuji Ito,Zahra Khedri,Yutaka Matsuda,Brian A. Mendelsohn
标识
DOI:10.1002/anie.201814215
摘要
Abstract 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI