Synthesis and biological activity of actin-depolymerizing substances

Kiyotake Suenaga, Hideo Kigoshi

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Aplyronine A 1 is a potent antitumor macrolide isolated from the sea hare Aplysia kurodai. Aplyronine A interacts with actin, one of the major proteins in cytoskeleton. We achieved total synthesis of aplyronine A and its 18 analogs and investigated structure-activity relationships. Analysis of the interaction of aplyronine analogs with actin by a photoaffinity labeling method and X-ray crystal structure analysis of actin complex with aplyronine A have been carried out. These results revealed that aplyronine A binds to actin at the hydrophobic cleft between subdomains 1 and 3 of actin. The binding mode of the macrolactone part of aplyronine A was different from previously reported macrolides. In addition, the trimethylserine moiety of aplyronine A, the essential functional group for cytotoxicity against HeLa S3 cells, was sticking out from a surface of actin-aplyronine A complex.

Original languageEnglish
Pages (from-to)1273-1281
Number of pages9
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume64
Issue number12
DOIs
Publication statusPublished - 2006 Dec

Keywords

  • Actin depolymerization
  • Antitumor macrolide
  • Crystal structure
  • Cytoskeleton
  • Cytotoxicity

ASJC Scopus subject areas

  • Organic Chemistry

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