Synthesis and biological activity of actin-depolymerizing substances

Kiyotake Suenaga; Hideo Kigoshi

doi:10.5059/yukigoseikyokaishi.64.1273

Synthesis and biological activity of actin-depolymerizing substances

Kiyotake Suenaga, Hideo Kigoshi

Department of Chemistry

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	1273-1281
Number of pages	9
Journal	Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume	64
Issue number	12
DOIs	https://doi.org/10.5059/yukigoseikyokaishi.64.1273
Publication status	Published - 2006 Dec

Keywords

Actin depolymerization
Antitumor macrolide
Crystal structure
Cytoskeleton
Cytotoxicity

ASJC Scopus subject areas

Organic Chemistry

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10.5059/yukigoseikyokaishi.64.1273

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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.",

keywords = "Actin depolymerization, Antitumor macrolide, Crystal structure, Cytoskeleton, Cytotoxicity",

author = "Kiyotake Suenaga and Hideo Kigoshi",

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AU - Kigoshi, Hideo

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AB - 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.

KW - Actin depolymerization

KW - Antitumor macrolide

KW - Crystal structure

KW - Cytoskeleton

KW - Cytotoxicity

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Synthesis and biological activity of actin-depolymerizing substances

Abstract

Keywords

ASJC Scopus subject areas

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