光親和性プローブを用いた抗腫瘍性天然物アプリロニンAの標的分子と作用機序の研究 Target Identification and Mode of Action Studies of an Antitumor Compound Aplyronine A by Using Photoaffinity Derivatives

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抄録

Actin is an essential cytoskeletal protein for the regulation of various cellular functions. A number of actin-stabilizing and depolymerizing agents have been discovered in marine invertebrates, and they show potent cytotoxicity. Among them, a polyketide macrolide aplyronine A has antitumor effects against xenograft in mice. However, the potent cytotoxicity and apoptogenic effect of aplyronine A was not entirely accounted for by its actin filament-severing properties, and its molecular targets and mechanisms of action remained unclear. We developed aplyronine A acetylene or biotin derivatives that bear an aryldiazirine group at the C34 terminus, which formed a covalent bond with actin. By using these chemical probes, we have showed that aplyronine A synergistically binds to tubulin in association with actin, and prevents spindle formation and mitosis in tumor cells. Our findings of aplyronine A will provide further insights into the molecular mechanisms of structurally diverse natural products that regulate cytoskeletal dynamics.

収録刊行物

  • 有機合成化学協会誌

    有機合成化学協会誌 73(2), 151-160, 2015

    社団法人 有機合成化学協会

各種コード

  • NII論文ID(NAID)
    130005129432
  • NII書誌ID(NCID)
    AN0024521X
  • 本文言語コード
    JPN
  • ISSN
    0037-9980
  • NDL 記事登録ID
    026084837
  • NDL 請求記号
    Z17-256
  • データ提供元
    NDL  J-STAGE 
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