Institute of Chemical Biology and Nanomedicine, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan, 410082, P. R. China.
Chembiochem. 2023 May 2;24(9):e202300077. doi: 10.1002/cbic.202300077. Epub 2023 Mar 30.
Antibody-oligonucleotide conjugates (AOCs) are important tools for drug development and biochemical analysis. However, the structural heterogeneity of AOCs synthesized through conventional coupling methods raises reproducibility and safety concerns in clinical trials. To address these issues, different covalent coupling approaches have been developed to synthesize AOCs with precise site-specificity and degree of conjugation. This Concept article categorizes these approaches as linker-free or linker-mediated and provides details on their chemistry and potential applications. Several factors, including site-specificity, conjugation control, accessibility, stability, and efficiency, are highlighted when evaluating the pros and cons of these approaches. The article also discusses the future of AOCs, including the development of better conjugation approaches to ensure stimuli-responsive release and the application of high-throughput methods to facilitate their development.
抗体-寡核苷酸偶联物 (AOCs) 是药物开发和生化分析的重要工具。然而，通过传统偶联方法合成的 AOCs 的结构异质性引起了临床试验中的重现性和安全性问题。为了解决这些问题，已经开发了不同的共价偶联方法来合成具有精确的位点特异性和偶联程度的 AOCs。本文将这些方法归类为无连接子或连接子介导，并详细介绍了它们的化学性质和潜在应用。在评估这些方法的优缺点时，突出了几个因素，包括位点特异性、偶联控制、可及性、稳定性和效率。本文还讨论了 AOCs 的未来，包括开发更好的偶联方法以确保刺激响应性释放，以及应用高通量方法来促进其发展。
