Alkyl lysophosphatidic acid and fluoromethylene phosphonate analogs as metabolically-stabilized agonists for LPA receptors.


:We describe an efficient method for the synthesis of alkyl lysophosphatidic acid (LPA) analogs as well as alkyl LPA mono- and difluoromethylene phosphonate analogs. Each alkyl LPA analog was evaluated for subtype-specific LPA receptor agonist activity using a cell migration assay for LPA(1) activation in cancer cells and an intracellular calcium mobilization assay for LPA(2) and LPA(3) activation. Alkyl LPAs induced pronounced cell migration activity with equivalent or higher potency than sn-1-oleoyl LPA, while the alkyl LPA fluoromethylene phosphonates proved to be less potent agonists in this assay. However, each alkyl LPA analog activated Ca(2+) release by activation of LPA(2) and LPA(3) receptors. Interestingly, the absolute configuration of the sn-2 hydroxyl group of the alkyl LPA analogs was not recognized by any of the three LPA receptors. The use of alkyl LPA analogs further expands the scope of structure-activity studies, which will better define LPA-LPA receptor interactions.


Bioorg Med Chem Lett


Xu Y,Tanaka M,Arai H,Aoki J,Prestwich GD




Has Abstract


2004-11-01 00:00:00














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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Lee JT,Chen DY,Yang Z,Ramos AD,Hsieh JJ,Bogyo M

    更新日期:2009-09-01 00:00:00

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    abstract::The dopamine D(3) receptor subtype has been targeted as a potential neurochemical modulator of the behavioral actions of psychomotor stimulants, such as cocaine. Previous synthetic studies provided structural requirements for high affinity binding to D(3) receptors which included a 2,3-dichloro-phenylpiperazine linked...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Newman AH,Cao J,Bennett CJ,Robarge MJ,Freeman RA,Luedtke RR

    更新日期:2003-07-07 00:00:00

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    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Girault S,Davioud-Charvet E,Salmon L,Berecibar A,Debreu MA,Sergheraert C

    更新日期:1998-05-19 00:00:00

  • Copper dipicolinates as peptidomimetic ligands for the Src SH2 domain.

    abstract::The introduction of copper chelates into peptide mimetics creates the Src SH2 binding ligands and paramagnetic complexes suitable for EPR studies of peptide protein interactions. The dipicolinic acid was attached to SH2 domain targeting fragments by two different linkers. ...

    journal_title:Bioorganic & medicinal chemistry letters

    pub_type: 杂志文章


    authors: Schmidt B,Jiricek J,Titz A,Ye G,Parang K

    更新日期:2004-08-16 00:00:00