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

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

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

    shin-ichi satoShin-Ichi Sato,youngjoo kwonYoungjoo Kwon,shinji kamisukiShinji Kamisuki,neeta srivastavaNeeta Srivastava,qian maoQian Mao,yoshinori kawazoeYoshinori Kawazoe,motonari uesugiMotonari Uesugi,

    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.

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

    s satoS Sato,y kwonY Kwon,s kamisukiS Kamisuki,n srivastavaN Srivastava,q maoQ Mao,y kawazoeY Kawazoe,m uesugiM Uesugi,

    For similar nucleic acids, nucleotides, and nucleosides: antisense elements (genetics): rna, antisense: rna, small interfering research abstracts see: nucleic acids, nucleotides, and nucleosides: antisense elements (genetics): rna, antisense: rna, small interfering research

    PUBMED ID PMID:

    MEDLINE DATE:

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

    PUBLICATION TYPE: Research Support, Non-U.S. Gov

    Journal: Journal of the American Chemical Society

    VOLUME: 129

    Page Numbers: 873-80

    Journal Abbreviation: J. Am. Chem. Soc.

    ISSN: 0002-7863

    DAY: 31

    MONTH: Jan

    YEAR: 2007

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

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 7503056

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

    KEYWORDS: RNA, Small Interfering

    MESH TERMS: pharmacology

    Chemical & Substance for Abstract: Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin. Information

    Substance Name: Lactoylglutathione Lyase

    Registry Number: EC 4.4.1.5

    Grant and Affiliation Information for Polyproline-rod approach to isolating protein targets of bioactive small molecules: isolation of a new target of indomethacin.

    AFFILIATION: The Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NCI

    GRANT: CA109277

    ACRONYM: CA

    MEDLINETA: J Am Chem Soc

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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