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Polyproline-rod approach to isolating protein targets of bioactive small molecules: Isolation of a new target of indomethacin

Title
Polyproline-rod approach to isolating protein targets of bioactive small molecules: Isolation of a new target of indomethacin
Authors
Sato S.-I.Kwon Y.Kamisuki S.Srivastava N.Mao Q.Kawazoe Y.Uesugi M.
Ewha Authors
권영주
SCOPUS Author ID
권영주scopus
Issue Date
2007
Journal Title
Journal of the American Chemical Society
ISSN
0002-7863JCR Link
Citation
vol. 129, no. 4, pp. 873 - 880
Indexed
SCI; SCIE; SCOPUS scopus
Abstract
Identification of protein targets of bioactive small molecules has been a technical hurdle of chemical genetics. Here we report a polyproline-rod approach to isolating protein targets of small molecules from cell lysates. The results indicate that insertion of a long, rigid polyproline helix between a small-molecule bait and a biotin tag boosts the capacity of affinity purification and thereby permits isolation of low-abundance or low-affinity proteins. In the course of the proof-of-concept experiments, we isolated glyoxalase 1 (GLO1) as a new target of indomethacin, a widely used antiinflammatory drug. Molecular biological experiments suggest that inhibition of GLO1 enzyme activity is related to the clinically recognized beneficial side effects of the indomethacin family of nonsteroidal antiinflammatory drugs. © 2007 American Chemical Society.
DOI
10.1021/ja0655643
Appears in Collections:
약학대학 > 약학과 > Journal papers
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