Mandipropamid as a chemical inducer of proximity for in vivo applications.


Journal

Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976

Informations de publication

Date de publication:
01 2022
Historique:
received: 09 09 2020
accepted: 13 10 2021
pubmed: 23 12 2021
medline: 23 2 2022
entrez: 22 12 2021
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 34934192
doi: 10.1038/s41589-021-00922-3
pii: 10.1038/s41589-021-00922-3
pmc: PMC8709788
doi:

Substances chimiques

Amides 0
Carboxylic Acids 0
Fungicides, Industrial 0
mandipropamid 11GP4ELK0U
Abscisic Acid 72S9A8J5GW

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

64-69

Informations de copyright

© 2021. The Author(s).

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Auteurs

Michael J Ziegler (MJ)

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg, Germany.

Klaus Yserentant (K)

Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany.
Faculty of Biosciences, Heidelberg University, Heidelberg, Germany.
Institute of Cardiovascular Sciences & School of Chemistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

Valentin Dunsing (V)

Institute of Biology and Biochemistry, University of Potsdam, Potsdam, Germany.

Volker Middel (V)

Institute of Biological and Chemical Systems (IBCS)-Biological Information Processing (BIP), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany.

Antoni J Gralak (AJ)

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany.

Kaisa Pakari (K)

Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany.

Jörn Bargstedt (J)

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.

Christoph Kern (C)

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany.

Annett Petrich (A)

Institute of Biology and Biochemistry, University of Potsdam, Potsdam, Germany.

Salvatore Chiantia (S)

Institute of Biology and Biochemistry, University of Potsdam, Potsdam, Germany.

Uwe Strähle (U)

Institute of Biological and Chemical Systems (IBCS)-Biological Information Processing (BIP), Karlsruhe Institute of Technology (KIT), Eggenstein-Leopoldshafen, Germany.

Dirk-Peter Herten (DP)

Institute of Physical Chemistry, Heidelberg University, Heidelberg, Germany.
Institute of Cardiovascular Sciences & School of Chemistry, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Centre of Membrane Proteins and Receptors (COMPARE), Universities of Birmingham and Nottingham, Midlands, UK.

Richard Wombacher (R)

Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany. wombacher@mr.mpg.de.
Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg, Germany. wombacher@mr.mpg.de.

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