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

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Sato S, Kwon Y, Kamisuki S, Srivastava N, Mao Q, Kawazoe Y, Uesugi M

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

J Am Chem Soc. 2007 Jan 31;129(4):873-80.

PubMed ID

17243824 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Indomethacin	Lactoylglutathione lyase	Protein	Humans	Unknown	Inhibitor	Details