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A Switchable Site-Specific Antibody Conjugate.

ABSTRACT: 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 ?GCN4-Fab conjugate that incorporates UAA p-acetylphenylalanine. The GCN4 peptide is used as a switch, and antibodies fused by GCN4 can direct the ?GCN4-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.

SUBMITTER: Lyu Z

PROVIDER: S-EPMC5910183 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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A Switchable Site-Specific Antibody Conjugate.

Lyu Zhigang Z Kang Lei L Buuh Zakey Yusuf ZY Jiang Dawei D McGuth Jeffrey C JC Du Juanjuan J Wissler Haley L HL Cai Weibo W Wang Rongsheng E RE

ACS chemical biology 20180228 4

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 t ...[more]

PMID: 29461804

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