Yamazaki Shunsuke, Matsuda Yutaka
Ajinomoto, Co., Inc., 1-1 Suzuki-cho, Kawasaki, Kanagawa, 210-8681, Japan.
Chem Biodivers. 2025 Mar;22(3):e202402113. doi: 10.1002/cbdv.202402113. Epub 2024 Nov 18.
Enzymatic modification, particularly utilizing lipoic acid ligase (LplA), has emerged as a transformative approach in biopharmaceuticals, enabling precise and site-specific protein modifications. This review delves into the innovative applications of LplA in antibody modifications, including the creation of antibody-drug conjugates (ADCs) and the advancement of tag-free conjugation techniques. LplA's ability to facilitate the incorporation of bioorthogonal groups and its adaptability to various substrates underscores its versatility. Key developments include the successful generation of dual-labeled antibodies and the application of LplA in modifying antibody fragments. Additionally, the review explores the potential for LplA to enhance the therapeutic efficacy of ADCs through improved drug-to-antibody ratios and site-specific payload attachment. The implications of these advancements are significant, suggesting that LplA-mediated modifications could lead to more effective and targeted antibody-based therapies. This review aims to provide a comprehensive overview of LplA's role in expanding the possibilities of enzymatic conjugation, setting the stage for future research and clinical applications.
酶促修饰，特别是利用硫辛酸连接酶（LplA），已成为生物制药领域一种变革性方法，能够实现精确且位点特异性的蛋白质修饰。本综述深入探讨了LplA在抗体修饰中的创新应用，包括抗体药物偶联物（ADC）的创建以及无标签偶联技术的进展。LplA促进生物正交基团掺入的能力及其对各种底物的适应性突出了其多功能性。关键进展包括成功生成双标记抗体以及LplA在修饰抗体片段中的应用。此外，本综述探讨了LplA通过提高药物与抗体比率和位点特异性负载连接来增强ADC治疗效果的潜力。这些进展的意义重大，表明LplA介导的修饰可能会带来更有效且靶向性更强的基于抗体的疗法。本综述旨在全面概述LplA在扩展酶促偶联可能性方面的作用，为未来的研究和临床应用奠定基础。
