Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, USA; Department of Biosciences, Rice University, 6100 Main Street, Houston, TX 77005, USA; Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, USA.
Cell Chem Biol. 2024 Mar 21;31(3):428-445. doi: 10.1016/j.chembiol.2023.09.004. Epub 2023 Oct 5.
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.
近年来，基于蛋白质的医学治疗领域取得了显著的发展。然而，人们对其细胞毒性限制、低亲和力、潜在免疫原性、低稳定性以及修饰这些蛋白质的挑战表示担忧。为了克服这些障碍，临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定点修饰，在不进行广泛工程改造的情况下提高其有效性。此外，这种创新方法能够根据临近情况对反应进行空间控制，促进治疗性蛋白质与其靶标之间不可逆的共价键形成。在解决治疗性蛋白质与其靶标之间经常出现的低亲和力以及特定蛋白质靶标小分子可用性有限等挑战方面，这种能力变得尤为有价值。因此，临近诱导化学正在重塑蛋白质药物制备领域，并推动新型蛋白质治疗的革命。
