Rational design of azepane-glycoside antibiotics targeting the bacterial ribosome.
Rational design of azepane-glycoside antibiotics targeting the bacterial ribosome.
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DOI：
10.1016/j.bmcl.2003.11.028
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发表时间：
2004-02
影响因子：
2.7
通讯作者：
S. Barluenga;K. Simonsen;E. S. Littlefield;B. Ayida;D. Vourloumis;G. Winters;Masayuki Takahashi;
中科院分区：
文献类型：
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作者：
S. Barluenga;K. Simonsen;E. S. Littlefield;B. Ayida;D. Vourloumis;G. Winters;Masayuki Takahashi;
天然氨基糖苷类抗生素对RNA的识别依赖于2-脱氧链霉胺（2-DOS）支架，该支架参与与核糖体解码位点靶标的特异性氢键。三维结构信息已被用于设计氮杂环庚烷-单糖苷类化合物，其是新型抗生素的结构单元，其中2-DOS被杂环支架取代。氮杂环庚烷糖苷在低微摩尔范围内表现出靶向结合和翻译抑制作用，并抑制金黄色葡萄球菌（包括氨基糖苷类耐药菌株）的生长。
RNA recognition by natural aminoglycoside antibiotics depends on the 2-deoxystreptamine (2-DOS) scaffold which participates in specific hydrogen bonds with the ribosomal decoding-site target. Three-dimensional structure information has been used for the design of azepane-monoglycosides, building blocks for novel antibiotics in which 2-DOS is replaced by a heterocyclic scaffold. Azepane-glycosides showed target binding and translation inhibition in the low micromolar range and inhibited growth of Staphylococcus aureus, including aminoglycoside-resistant strains.