Mandipropamid as a chemical inducer of proximity for in vivo applications

Michael J. Ziegler, Klaus Yserentant, Valentin Dunsing, Volker Middel, Antoni J. Gralak, Kaisa Pakari, Jörg Bargstedt, Christoph Kern, Annett Petrich, Salvatore Chiantia, Uwe Strähle, Dirk-Peter Herten, Richard Wombacher

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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.
Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalNature Chemical Biology
Issue number1
Early online date21 Dec 2021
Publication statusPublished - Jan 2022

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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