Advancing protein therapeutics through proximity-induced chemistry.
Advancing protein therapeutics through proximity-induced chemistry.
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DOI：
10.1016/j.chembiol.2023.09.004
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发表时间：
2023-10
影响因子：
8.6
通讯作者：
Linqi Cheng;Yixian Wang;Yiming Guo;Sophie S. Zhang;Han Xiao
中科院分区：
文献类型：
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作者：
Linqi Cheng;Yixian Wang;Yiming Guo;Sophie S. Zhang;Han Xiao
近年来，基于蛋白质的医疗领域取得了显着的增长。然而，人们对细胞毒性限制、低亲和力、潜在的免疫原性、低稳定性以及修饰这些蛋白质的挑战产生了担忧。为了克服这些障碍，邻近诱导化学已成为推进蛋白质治疗的下一代策略。该方法允许使用治疗剂对蛋白质进行位点特异性修饰，从而无需进行大量工程改造即可提高其有效性。此外，这种创新方法能够根据接近度对反应进行空间控制，促进治疗蛋白与其靶标之间形成不可逆共价键。这种能力在解决诸如治疗性蛋白质与其靶标之间经常遇到的低亲和力以及针对特定蛋白质靶标的小分子的可用性有限等挑战时变得特别有价值。因此，邻近诱导化学正在重塑蛋白质药物制备领域，并推动新型蛋白质疗法的革命。
Recent years have seen a remarkable growth in the field of protein-based medical treatments. Nevertheless, concerns have arisen regarding the cytotoxicity limitations, low affinity, potential immunogenicity, low stability, and challenges to modify these proteins. To overcome these obstacles, proximity-induced chemistry has emerged as a next-generation strategy for advancing protein therapeutics. This method allows site-specific modification of proteins with therapeutic agents, improving their effectiveness without extensive engineering. In addition, this innovative approach enables spatial control of the reaction based on proximity, facilitating the formation of irreversible covalent bonds between therapeutic proteins and their targets. This capability becomes particularly valuable in addressing challenges such as the low affinity frequently encountered between therapeutic proteins and their targets, as well as the limited availability of small molecules for specific protein targets. As a result, proximity-induced chemistry is reshaping the field of protein drug preparation and propelling the revolution in novel protein therapeutics.