Discovery of Natural Products Possessing Selective Eukaryotic Readthrough Activity: 3-epi-Deoxynegamycin and Its Leucine Adduct
Discovery of Natural Products Possessing Selective Eukaryotic Readthrough Activity: 3-epi-Deoxynegamycin and Its Leucine Adduct
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具有选择性真核通读活性的天然产物的发现：3-表-脱氧霉素及其亮氨酸加合物
DOI：
10.1002/cmdc.201402208
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发表时间：
2014
期刊：
影响因子：
3.4
通讯作者：
Yoshio Hayashi
中科院分区：
文献类型：
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作者：
Akihiro Taguchi;Keisuke Hamada;Masaya Kotake;Masataka Shiozuka;Hidemasa Nakaminami;Thanigaimalai Pillaiyar;Kentaro Takayama;Fumika Yakushiji;Norihisa Noguchi;Takeo Usui;Ryoichi Matsuda;Yoshio Hayashi
在这里，我们报告了首次发现的天然读出产品，不显示抗菌活性。37年前分离的两种天然负碳素，3 -外延-脱氧负碳素及其亮氨酸加合物，被发现是对抗真核生物无义突变的有效穿透剂，而不是原核生物，但没有抗菌活性。这些结果表明，这些化合物是开发针对无义介导的遗传疾病的通读药物的有价值的线索，而不会导致耐药细菌的出现。
Herein we report the first discovery of natural readthrough products that do not display antimicrobial activity. Two natural negamycins, 3‐epi‐deoxynegamycin and its leucine adduct, isolated 37 years ago, were found to be potent readthrough agents against nonsense mutations of eukaryotes, but not prokaryotes, without displaying antimicrobial activity. These results suggest that the compounds are valuable leads for the development of readthrough drugs against nonsense‐mediated genetic diseases without the potential for contributing to the emergence of drug‐resistant bacteria.