In response to environmental and other stresses, the σ54subunit of bacterial RNA polymerase (RNAP) controls expression of several genes that play a significant role in the virulence of both plant and animal pathogens. Recruitment of σ54to RNAP initiates promoter-specific transcription via the double-stranded DNA denaturation mechanism of the cofactor. The RpoN box, a recognition helix found in the C-terminal region of σ54, has been identified as the component necessary for major groove insertion at the −24 position of the promoter. We employed the hydrocarbon stapled peptide methodology to design and synthesize stapled σ54peptides capable of penetrating Gram-negative bacteria, binding the σ54promoter, and blocking the interaction between endogenous σ54and its target DNA sequence, thereby reducing transcription and activation of σ54response genes.

中文翻译：

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基于RpoN的吻合肽抑制细菌基因转录。

响应环境和其他压力，细菌RNA聚合酶（RNAP）的σ54亚基控制着几种基因的表达，这些基因在动植物病原体的毒性中起着重要作用。σ54到RNAP的募集通过辅因子的双链DNA变性机制启动启动子特异性转录。RpoN框是在σ54的C端区域发现的识别螺旋，已被鉴定为在启动子的-24位置插入主要凹槽所必需的组件。我们采用了碳氢化合物固定肽方法来设计和合成能够穿透革兰氏阴性细菌，结合σ54启动子并阻断内源σ54及其靶DNA序列之间相互作用的固定σ54肽，从而减少了σ54响应基因的转录和激活。