{"id":110,"date":"2021-11-25T15:46:32","date_gmt":"2021-11-25T06:46:32","guid":{"rendered":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/WordPress\/?p=110"},"modified":"2021-11-25T15:58:38","modified_gmt":"2021-11-25T06:58:38","slug":"structure-optimization-of-gatastatin-for-the-development-of-%ce%b3-tubulin-specific-inhibitor","status":"publish","type":"post","link":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/archives\/110","title":{"rendered":"Structure Optimization of Gatastatin for the Development of \u03b3-Tubulin-Specific Inhibitor"},"content":{"rendered":"\n<p>Kana Shintani, Haruna Ebisu, Minagi Mukaiyama, Taisei Hatanaka, Takumi Chinen, Daisuke Takao, Yoko Nagumo, Akira Sakakura, Ichiro Hayakawa,* Takeo Usui*&nbsp;&nbsp;<br><em>ACS Med. Chem. Lett.<\/em><strong>2020<\/strong>,&nbsp;<em>11<\/em>&nbsp;(6), 1125\u20131129.&nbsp; (Published online:&nbsp;March&nbsp;30, 2020)&nbsp;<br><a href=\"https:\/\/doi.org\/10.1021\/acsmedchemlett.9b00526\">DOI: 10.1021\/acsmedchemlett.9b00526&nbsp;<img decoding=\"async\" src=\"http:\/\/www.cc.okayama-u.ac.jp\/~sakakura\/bioorgchem\/_src\/10556\/img20180629093542651479.png\" alt=\"LinkIcon\"><\/a><\/p>\n\n\n\n<figure class=\"wp-block-image size-full\"><img loading=\"lazy\" decoding=\"async\" width=\"500\" height=\"254\" src=\"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/WordPress\/wp-content\/uploads\/2021\/07\/gatastatin.gif\" alt=\"\" class=\"wp-image-111\"\/><\/figure>\n\n\n\n<p>Gatastatin (O7-benzyl glaziovianin A) is a \u03b3-tubulin-specific inhibitor that is used to investigate \u03b3-tubulin function in cells. We have previously reported that the unsubstituted phenyl ring of the O7-benzyl group in gatastatin is important for \u03b3-tubulin inhibition. To obtain further structural information regarding \u03b3-tubulin inhibition, we synthesized several gatastatin derivatives containing a fixed O7-benzyl moiety. Modifications of the B-ring resulted in drastic decrease in cytotoxicity, abnormal spindle formation activity, and inhibition of microtubule (MT) nucleation. In contrast, various O6-alkylated gatastatin derivatives showed potent cytotoxicity, induced abnormal spindle formation, and inhibited MT nucleation. We had previously reported that O6-benzyl glaziovianin A is a potent \u03b1\/\u03b2-tubulin inhibitor; thus, these new results suggest that the O6-position restricts affinity for \u03b1\/\u03b2- and \u03b3-tubulin. Considering that an O7-benzyl group increases specificity for \u03b3-tubulin, more potent and specific \u03b3-tubulin inhibitors can be generated through O6-modifications of gatastatin.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Kana Shintani, Haruna Ebisu, Minagi Mukaiyama, Taisei Hatanaka, Takumi Chinen, Daisuke Takao, Yoko Nagumo, Aki [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":111,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"vkexunit_cta_each_option":"","footnotes":""},"categories":[6],"tags":[],"class_list":["post-110","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"_links":{"self":[{"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/posts\/110","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/comments?post=110"}],"version-history":[{"count":2,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/posts\/110\/revisions"}],"predecessor-version":[{"id":265,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/posts\/110\/revisions\/265"}],"wp:featuredmedia":[{"embeddable":true,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/media\/111"}],"wp:attachment":[{"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/media?parent=110"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/categories?post=110"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/achem.okayama-u.ac.jp\/bioorgchem\/wp-json\/wp\/v2\/tags?post=110"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}