Abstract Virtual screening of all possible tripeptide analogues of chloramphenicol was performed using molecular docking to evaluate their affinity to bacterial ribosomes. Chloramphenicol analogues that demonstrated the lowest calculated energy of interaction with ribosomes were synthesized. Chloramphenicol amine (CAM) derivatives, which contained specific peptide fragments from the proline-rich antimicrobial peptides were produced. It was demonstrated using displacement of the fluorescent erythromycin analogue from its complex with ribosomes that the novel peptide analogues of chloramphenicol were able to bind bacterial ribosome; all the designed tripeptide analogues and one of the chloramphenicol amine derivatives containing fragment of the proline-rich antimicrobial peptides exhibited significantly greater affinity to Escherichia coli ribosome than chloramphenicol. Correlation between the calculated and experimentally evaluated levels of the ligand efficiencies was observed. In vitro protein biosynthesis inhibition assay revealed, that the RAW-CAM analogue shows activity at the level of chloramphenicol. These data were confirmed by the chemical probing assay, according to which binding pattern of this analogue in the nascent peptide exit tunnel was similar to chloramphenicol.

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氯霉素阳离子肽类似物与核糖体的相互作用

摘要 使用分子对接对所有可能的氯霉素三肽类似物进行虚拟筛选，以评估它们对细菌核糖体的亲和力。合成了显示与核糖体相互作用的最低计算能量的氯霉素类似物。产生了氯霉素胺 (CAM) 衍生物，其中包含来自富含脯氨酸的抗菌肽的特定肽片段。使用从其与核糖体的复合物中置换荧光红霉素类似物证明，氯霉素的新型肽类似物能够结合细菌核糖体；所有设计的三肽类似物和一种含有富含脯氨酸的抗菌肽片段的氯霉素胺衍生物对大肠杆菌核糖体的亲和力显着高于氯霉素。观察到计算的和实验评估的配体效率水平之间的相关性。体外蛋白质生物合成抑制试验表明，RAW-CAM 类似物显示出氯霉素水平的活性。这些数据通过化学探测分析得到证实，根据该分析，这种类似物在新生肽出口隧道中的结合模式与氯霉素相似。RAW-CAM 类似物显示出氯霉素水平的活性。这些数据通过化学探测分析得到证实，根据该分析，这种类似物在新生肽出口隧道中的结合模式与氯霉素相似。RAW-CAM 类似物显示出氯霉素水平的活性。这些数据通过化学探测分析得到证实，根据该分析，这种类似物在新生肽出口隧道中的结合模式与氯霉素相似。