Abstract：
Efficient and precise chemical protein modification methods are highly sought after in biotechnology. However, chemically distinguishing a single site within a large protein is challenging. This study introduces a Copper Assisted Sequence-specific Conjugation Tag (CAST) method, enabling rapid (second order rate 8.1 M-1s-1) and site-specific chemical modification of the protein backbone with pinpoint accuracy. The versatility of this method is demonstrated through the preparation of antibody-drug conjugates, showcasing high plasma stability and potent efficacy in both in vitro and in vivo settings. Thus, CAST emerges as an efficient and quantitative approach for attaching payloads to large, native proteins.
摘要：
高效和精确的化学蛋白质修饰方法在生物技术中备受追捧。然而,用化学方法区分大蛋白质中的单个位点是具有挑战性的。本研究介绍了一种铜辅助序列特异性缀合标签(CAST)方法，使蛋白质骨架的快速（二阶速率8.1M-1s-1）和位点特异性化学修饰具有精确的准确性。通过制备抗体-药物缀合物证明了该方法的多功能性，在体外和体内设置中显示出高血浆稳定性和有效功效。因此，CAST作为一种有效和定量的方法出现，用于将有效载荷附加到大的，天然蛋白质。
