Hussain Ahmad Fawzi, Grimm Armin, Sheng Wenjie, Zhang Chaoyu, Al-Rawe Marwah, Bräutigam Karen, Abu Mraheil Mobarak, Zeppernick Felix, Meinhold-Heerlein Ivo
Department of Gynecology and Obstetrics, Medical Faculty, Justus-Liebig-University Giessen, 35392 Giessen, Germany.
Department of Gynecology and Obstetrics, University Medical Center Schleswig-Holstein, Campus Lübeck, 23562 Lübeck, Germany.
Pharmaceuticals (Basel). 2021 Apr 8;14(4):343. doi: 10.3390/ph14040343.
In the last few decades, antibody-based diagnostic and therapeutic applications have been well established in medicine and have revolutionized cancer managements by improving tumor detection and treatment. Antibodies are unique medical elements due to their powerful properties of being able to recognize specific antigens and their therapeutic mechanisms such as blocking specific pathways, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity. Furthermore, modification techniques have paved the way for improving antibody properties and to develop new classes of antibody-conjugate-based diagnostic and therapeutic agents. These techniques allow arming antibodies with various effector molecules. However, these techniques are utilizing the most frequently used amino acid residues for bioconjugation, such as cysteine and lysine. These bioconjugation approaches generate heterogeneous products with different functional and safety profiles. This is mainly due to the abundance of lysine and cysteine side chains. To overcome these limitations, different site-direct conjugation methods have been applied to arm the antibodies with therapeutic or diagnostics molecules to generate unified antibody conjugates with tailored properties. This review summarizes some of the enzyme-based site-specific conjugation approaches.
在过去几十年中，基于抗体的诊断和治疗应用在医学领域已得到充分确立，并通过改善肿瘤检测和治疗彻底改变了癌症管理方式。抗体是独特的医学元件，因为它们具有识别特定抗原的强大特性以及诸如阻断特定途径、抗体依赖性细胞毒性和补体依赖性细胞毒性等治疗机制。此外，修饰技术为改善抗体特性以及开发新型基于抗体偶联物的诊断和治疗剂铺平了道路。这些技术允许用各种效应分子武装抗体。然而，这些技术利用的是生物共轭中最常用的氨基酸残基，如半胱氨酸和赖氨酸。这些生物共轭方法会产生具有不同功能和安全性的异质产物。这主要是由于赖氨酸和半胱氨酸侧链的丰度。为克服这些限制，已应用不同的位点直接共轭方法用治疗或诊断分子武装抗体，以生成具有定制特性的统一抗体偶联物。本综述总结了一些基于酶的位点特异性共轭方法。
