Inhibition of Bacterial Gene Transcription with an RpoN-Based Stapled Peptide
Inhibition of Bacterial Gene Transcription with an RpoN-Based Stapled Peptide
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DOI：
10.1016/j.chembiol.2018.05.007
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发表时间：
2018-09-20
影响因子：
8.6
通讯作者：
Bernal, Federico
中科院分区：
文献类型：
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作者：
Payne, Sterling R.;Pau, Daniel, I;Bernal, Federico
细菌RNA聚合酶（RNAP）的sigma（54）亚基在环境和其他胁迫下控制几个基因的表达，这些基因在植物和动物病原体的毒力中起重要作用。σ（54）向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盒是在sigma（54）的C-末端区域中发现的识别螺旋，已被鉴定为在启动子的24位处插入大沟所必需的组分。我们采用烃钉合肽方法来设计和合成能够穿透革兰氏阴性细菌、结合sigma（54）启动子并阻断内源性sigma（54）与其靶DNA序列之间的相互作用的钉合sigma（54）肽，从而减少sigma（54）应答基因的转录和激活。
In response to environmental and other stresses, the sigma(54) subunit 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 sigma(54) to 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 sigma(54), 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 sigma(54) peptides capable of penetrating Gram-negative bacteria, binding the sigma(54) promoter, and blocking the interaction between endogenous sigma(54) and its target DNA sequence, thereby reducing transcription and activation of sigma(54) response genes.