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

ABSTRACT: 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.

SUBMITTER: Ado G

PROVIDER: S-EPMC9116451 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Ado Genyir G Noda Naotaka N Vu Hue T HT Perron Amelie A Mahapatra Amarjyoti D AD Arista Karla Pineda KP Yoshimura Hideaki H Packwood Daniel M DM Ishidate Fumiyoshi F Sato Shin-Ichi SI Ozawa Takeaki T Uesugi Motonari M

Chemical science 20220420 19

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 ...[more]

PMID: 35694339

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