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

著者 Liu Y , Fares M , Dunham NP , Gao Z , Miao K , Jiang X , Bollinger SS , Boal AK , Zhang X
Angew Chem Int Ed Engl.2017 May 29 ; ():.
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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. Herein we report a fluorogenic protein sensor that detects 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 anti-cancer 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.
PMID: 28557281 [PubMed - as supplied by publisher]
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