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

• 北 将樹

  筑波大学数理物質系

• 木越 英夫

  筑波大学数理物質系

書誌事項

タイトル別名

• Target Identification and Mode of Action Studies of an Antitumor Compound Aplyronine A by Using Photoaffinity Derivatives
• ヒカリ シンワセイ プローブ オ モチイタ コウシュヨウセイ テンネンブツ アプリロニン A ノ ヒョウテキ ブンシ ト サヨウ キジョ ノ ケンキュウ

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

  公益社団法人 有機合成化学協会

キーワード

• antitumor macrolide
• photoaffinity probe
• target identification
• cytoskeletal protein
• protein-protein interaction

詳細情報

• CRID: 1390001205341346944
• NII論文ID: 130005129432
• NII書誌ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.73.151
• ISSN: 18836526
• ISSN: 00379980
• NDL書誌ID: 026084837
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026084837
• 本文言語コード: ja
• データソース種別:
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