Fournier Léxane, Guarnera Enrico, Kolmar Harald, Becker Stefan
Early Protein Supply and Characterization, Merck Healthcare KGaA, Darmstadt, Germany; Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.
Antibody Discovery and Protein Engineering, Merck Healthcare KGaA, Darmstadt, Germany.
Trends Pharmacol Sci. 2025 Apr;46(4):311-323. doi: 10.1016/j.tips.2024.10.007. Epub 2024 Nov 18.
Allostery represents a fundamental mechanism in protein regulation, enabling modulation of protein function from sites distal to the active site. While traditionally explored in the context of small molecules, allosteric modulation is gaining traction as a main mode of action in the realm of antibodies, which offer enhanced specificity and reduced toxicity. This review delves into the rapidly growing field of allosteric antibodies, highlighting recent therapeutic advancements and novel druggability avenues. We also explore the potential of these antibodies as innovative tools in drug discovery and discuss contemporary strategies for designing novel allosteric antibodies, leveraging state-of-the-art computational approaches.
变构是蛋白质调节中的一种基本机制，能够从活性位点远端的位点调节蛋白质功能。虽然传统上是在小分子的背景下进行研究，但变构调节作为抗体领域的一种主要作用模式正越来越受到关注，抗体具有更高的特异性和更低的毒性。本综述深入探讨了快速发展的变构抗体领域，重点介绍了最近的治疗进展和新的可成药途径。我们还探讨了这些抗体作为药物发现中创新工具的潜力，并讨论了利用最先进的计算方法设计新型变构抗体的当代策略。
