Affinity-Directed Site-Specific Protein Labeling and Its Application to Antibody-Drug Conjugates

초록

Chemically modified proteins have diverse applications; however, conventional chemo-selective methods often yield heterogeneously labeled products. To address this limitation, site-specific protein labeling holds significant potential, driving extensive research in this area. Nevertheless, site-specific modification of native proteins remains challenging owing to the complexity of their functional groups. Therefore, a method for site-selective labeling of intact proteins is aimed to design. In this study, a novel approach to traceless affinity-directed intact protein labeling is established, which leverages small binding proteins and genetic code expansion technology. By applying this method, a site-specific antibody labeling with a drug, which leads to the production of highly effective antibody-drug conjugates specifically targeting breast cancer cell lines is achieved. This approach enables traceless conjugation of intact target proteins, which is a critical advantage in pharmaceutical applications. Furthermore, small helical binding proteins can be easily engineered for various target proteins, thereby expanding their potential applications in diverse fields. This innovative approach represents a significant advancement in site-specific modification of native proteins, including antibodies. It also bears immense potential for facilitating the development of therapeutic agents for various diseases. A novel method for precise, affinity-driven site-specific protein labeling, leveraging small binding proteins and genetic code expansion technology is presented. This innovative approach enables the conjugation of intact target proteins, with a specific emphasis on its utility in advancing the field of antibody-drug conjugates. The inherent versatility of these binding proteins unveils promising avenues for a wide spectrum of applications.image

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