Intracellular protein-responsive supramolecules: Protein sensing and in-cell construction of inhibitor assay system

Tatsuyuki Yoshii, Keigo Mizusawa, Yousuke Takaoka, Itaru Hamachi

研究成果: Article査読

56 被引用数 (Scopus)

抄録

Supramolecular nanomaterials responsive to specific intracellular proteins should be greatly promising for protein sensing and imaging, controlled drug release or dynamic regulation of cellular processes. However, valid design strategies to create useful probes are poorly developed, particularly for proteins inside living cells as targets. We recently reported a unique supramolecular strategy for specific protein detection using self-assembling fluorescent probes consisting of a protein ligand and a fluorophore on the live cell surface, as well as in test tube settings. Herein, we discovered that our self-assembled supramolecular probes having a rhodamine derivative (tetramethylrhodamine or rhodamine-green) can incorporate and stay as less-fluorescent aggregates inside the living cells, so as to sense the protein activity in a reversible manner. Using the overexpressed model protein (dihydrofolate reductase), we demonstrated that this turn-on/off mode is controlled by selective ligand-protein recognition inside the live cells. Not only such a model protein, but also endogenous human carbonic anhydrase and heat shock protein 90 were specifically visualized in living mammalian cells, by use of the similar ligand-tethered supramolecular probes. Furthermore, such reversibility allowed us to intracellularly construct a unique system to evaluate the inhibitors affinity toward specific endogenous proteins in live cells, highlighting the potential of dynamic supramolecules as novel intelligent biomaterials.

本文言語English
ページ(範囲)16635-16642
ページ数8
ジャーナルJournal of the American Chemical Society
136
47
DOI
出版ステータスPublished - 2014 11月 26

ASJC Scopus subject areas

  • 触媒
  • 化学 (全般)
  • 生化学
  • コロイド化学および表面化学

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