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AgHalo: A Facile Fluorogenic Sensor to Detect Drug‐Induced Proteome Stress
Author(s) -
Liu Yu,
Fares Matthew,
Dunham Noah P.,
Gao Zi,
Miao Kun,
Jiang Xueyuan,
Bollinger Samuel S.,
Boal Amie K.,
Zhang Xin
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201702417
Subject(s) - proteome , cytotoxicity , programmed cell death , drug , chemistry , human proteome project , proteomics , computational biology , microbiology and biotechnology , biology , apoptosis , biochemistry , pharmacology , in vitro , gene
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.