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Lyu Z , Kang L , Buuh ZY , Jiang D , McGuth JC , Du J , Wissler HL , Cai W , Wang RE
A Switchable Site-Specific Antibody Conjugate
ACS Chem Biol. 2018 Apr 20;13(4) :958-964
PMID: 29461804    PMCID: PMC5910183   
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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 alphaGCN4-Fab conjugate that incorporates UAA p-acetylphenylalanine. The GCN4 peptide is used as a switch, and antibodies fused by GCN4 can direct the alphaGCN4-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.
1554-8937 Lyu, Zhigang Kang, Lei Buuh, Zakey Yusuf Jiang, Dawei Orcid: 0000-0002-4072-0075 McGuth, Jeffrey C Du, Juanjuan Wissler, Haley L Cai, Weibo Orcid: 0000-0003-4641-0833 Wang, Rongsheng E Orcid: 0000-0002-5749-7447 P30 CA014520/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States ACS Chem Biol. 2018 Apr 20;13(4):958-964. doi: 10.1021/acschembio.8b00107. Epub 2018 Feb 28.