Linezolid and tedizolid are oxazolidinones with established clinical utility for the treatment of Gram-positive pathogens. Over time it has become apparent that even modest structural changes to the core phenyl oxazolidinone leads to drastic changes in biological activity. Consequently, the structure–activity relationship around the core oxazolidinone is constantly evolving, often reflected with new structural motifs present in nascent oxazolidinones. Herein we describe the use of cryo-electron microscopy to examine the differences in binding of several functionally different oxazolidinones in the hopes of enhanced understanding of their SAR. Tedizolid, radezolid, T145, and contezolid have been examined within the peptidyl transferase center (PTC) of the 50S ribosomal subunit from methicillin resistant Staphylococcus aureus. The ribosome–antibiotic complexes were resolved to a resolution of around 3 Å enabling unambiguous assignment of how each antibiotic interacts with the PTC.

中文翻译：

---

使用Cryo-EM表征恶唑烷酮类抗生素的核心核糖体结合区。

利奈唑胺和泰替唑酯是恶唑烷酮，在治疗革兰氏阳性病原体方面具有确定的临床效用。随着时间的流逝，很明显，即使对核心苯基恶唑烷酮的适度结构变化也会导致生物学活性的急剧变化。因此，围绕恶唑烷酮核心的结构-活性关系不断发展，通常反映在新生的恶唑烷酮中存在新的结构基序。在这里，我们描述了使用冷冻电子显微镜检查几种功能不同的恶唑烷酮在结合方面的差异，以期加深对它们的SAR的了解。已在耐甲氧西林的50S核糖体亚基的肽基转移酶中心（PTC）内检查了替地唑利德，雷地唑利德，T145和孔替佐利德金黄色葡萄球菌。核糖体-抗生素复合物的分离度约为3Å，可以明确分配每种抗生素与PTC的相互作用方式。