AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress

Yu Liu, Matthew Fares, Noah P. Dunham, Zi Gao, Kun Miao, Xueyuan Jiang, Samuel S. Bollinger, Amie K. Boal, Xin Zhang

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins.

Original languageEnglish (US)
Pages (from-to)8672-8676
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number30
DOIs
StatePublished - Jan 1 2017

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

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