Direct control of protein interactions by chemically induced protein proximity holds great potential for both cell and synthetic biology as well as therapeutic applications. Low toxicity, orthogonality and excellent cell permeability are important criteria for chemical inducers of proximity (CIPs), in particular for in vivo applications. Here, we present the use of the agrochemical mandipropamid (Mandi) as a highly efficient CIP in cell culture systems and living organisms. Mandi specifically induces complex formation between a sixfold mutant of the plant hormone receptor pyrabactin resistance 1 (PYR1) and abscisic acid insensitive (ABI). It is orthogonal to other plant hormone-based CIPs and rapamycin-based CIP systems. We demonstrate the applicability of the Mandi system for rapid and efficient protein translocation in mammalian cells and zebrafish embryos, protein network shuttling and manipulation of endogenous proteins.

通过化学诱导的蛋白质接近直接控制蛋白质相互作用对于细胞和合成生物学以及治疗应用具有巨大的潜力。低毒性、正交性和优异的细胞渗透性是接近化学诱导剂 (CIP) 的重要标准，特别是对于体内应用。在这里，我们介绍了农用化学品 mandipropamid (Mandi) 在细胞培养系统和活生物体中作为高效 CIP 的用途。Mandi 特异性诱导植物激素受体 pyrabactin 抗性 1 (PYR1) 的六倍突变体与脱落酸不敏感 (ABI) 之间的复合物形成。它与其他基于植物激素的 CIP 和基于雷帕霉素的 CIP 系统正交。