PUBLICATION

Mandipropamid as a chemical inducer of proximity for in vivo applications

Authors
Ziegler, M.J., Yserentant, K., Dunsing, V., Middel, V., Gralak, A.J., Pakari, K., Bargstedt, J., Kern, C., Petrich, A., Chiantia, S., Strähle, U., Herten, D.P., Wombacher, R.
ID
ZDB-PUB-211224-5
Date
2021
Source
Nature Chemical Biology   18(1): 64-69 (Journal)
Registered Authors
Middel, Volker, Strähle, Uwe
Keywords
none
MeSH Terms
  • Abscisic Acid/metabolism
  • Amides/pharmacology*
  • Animals
  • Carboxylic Acids/pharmacology*
  • Dimerization
  • Fungicides, Industrial/pharmacology*
  • Zebrafish/embryology
PubMed
34934192 Full text @ Nat. Chem. Biol.
Abstract
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.
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Human Disease / Model
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