Discovery of a phase-separating small molecule that selectively sequesters tubulin in cells.


Journal

Chemical science
ISSN: 2041-6520
Titre abrégé: Chem Sci
Pays: England
ID NLM: 101545951

Informations de publication

Date de publication:
18 May 2022
Historique:
received: 23 12 2021
accepted: 25 03 2022
entrez: 13 6 2022
pubmed: 14 6 2022
medline: 14 6 2022
Statut: epublish

Résumé

Phase-separated membraneless organelles or biomolecular condensates play diverse functions in cells, however recapturing their characteristics using small organic molecules has been a challenge. In the present study, cell-lysate-based screening of 843 self-assembling small molecules led to the discovery of a simple organic molecule, named huezole, that forms liquid droplets to selectively sequester tubulin. Remarkably, this small molecule enters cultured human cells and prevents cell mitosis by forming tubulin-concentrating condensates in cells. The present study demonstrates the feasibility of producing a synthetic condensate out of non-peptidic small molecules for exogenous control of cellular processes. The modular structure of huezole provides a framework for designing a class of organelle-emulating small molecules.

Identifiants

pubmed: 35694339
doi: 10.1039/d1sc07151c
pii: d1sc07151c
pmc: PMC9116451
doi:

Types de publication

Journal Article

Langues

eng

Pagination

5760-5766

Informations de copyright

This journal is © The Royal Society of Chemistry.

Déclaration de conflit d'intérêts

There are no conflicts to declare.

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Auteurs

Genyir Ado (G)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Graduate School of Medicine, Kyoto University Uji Kyoto 611-0011 Japan.

Naotaka Noda (N)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Graduate School of Medicine, Kyoto University Uji Kyoto 611-0011 Japan.

Hue T Vu (HT)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Graduate School of Medicine, Kyoto University Uji Kyoto 611-0011 Japan.

Amelie Perron (A)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Kyoto 606-8501 Japan.

Amarjyoti D Mahapatra (AD)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.

Karla Pineda Arista (KP)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Graduate School of Medicine, Kyoto University Uji Kyoto 611-0011 Japan.

Hideaki Yoshimura (H)

Department of Chemistry, School of Science, The University of Tokyo Tokyo 113-0033 Japan.

Daniel M Packwood (DM)

Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Kyoto 606-8501 Japan.

Fumiyoshi Ishidate (F)

Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Kyoto 606-8501 Japan.

Shin-Ichi Sato (SI)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.

Takeaki Ozawa (T)

Department of Chemistry, School of Science, The University of Tokyo Tokyo 113-0033 Japan.

Motonari Uesugi (M)

Institute for Chemical Research, Kyoto University Uji Kyoto 611-0011 Japan uesugi@scl.kyoto-u.ac.jp.
Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University Kyoto 606-8501 Japan.
School of Pharmacy, Fudan University Shanghai 201203 China.

Classifications MeSH