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ACS Chem Biol. 2018 Apr 20;13(4):958-964. doi: 10.1021/acschembio.8b00107. Epub 2018 Feb 28.

A Switchable Site-Specific Antibody Conjugate.

Author information

Department of Chemistry , Temple University , 1901 N. 13th Street , Philadelphia , Pennsylvania 19122 , United States.
Department of Nuclear Medicine , Peking University First Hospital , Beijing , 100034 , China.
Departments of Radiology and Medical Physics , University of Wisconsin-Madison , Madison , Wisconsin 53705 , United States.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Health Science Center , Shenzhen University , Shenzhen , 518060 , China.
School of Pharmaceutical Sciences , Tsinghua University , Beijing , 100084 , China.


Genetic incorporation of unnatural amino acids (UAAs) provides a unique approach to the synthesis of site-specific antibody conjugates that are homogeneous and better defined constructs than random conjugates. Yet, the yield varies for every antibody, and the process is costly and time-consuming. We have developed a switchable αGCN4-Fab conjugate that incorporates UAA p-acetylphenylalanine. The GCN4 peptide is used as a switch, and antibodies fused by GCN4 can direct the αGCN4-Fab conjugate to target different cancer cells for diagnosis, imaging, or therapeutic treatment. More importantly, this switchable conjugate demonstrated an impressive potential for pretargeted imaging in vivo. This approach illustrates the utility of an orthogonal switch as a general strategy to endow versatility to a single antibody conjugate, which should facilitate the application of UAA-based site-specific conjugates for a host of biomedical uses in the future.

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