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.

中文翻译：

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可切换位点特异性抗体偶联物

非天然氨基酸（UAA）的遗传掺入为合成位点特异性抗体偶联物提供了独特的方法，该抗体是均质的且比随机偶联物定义更好的构建体。然而，每种抗体的产量各不相同，并且该过程既昂贵又费时。我们已经开发了一种包含UAA对乙酰基苯丙氨酸的可转换αGCN4-Fab共轭物。GCN4肽用作开关，与GCN4融合的抗体可以指导αGCN4-Fab共轭物靶向不同的癌细胞，以进行诊断，成像或治疗。更重要的是，这种可切换的共轭物在体内预定位成像方面显示出令人印象深刻的潜力。这种方法说明了正交开关作为赋予单一抗体偶联物多功能性的一般策略的实用性，这将有助于将来基于UAA的位点特异性偶联物在许多生物医学用途中的应用。