biostudies-literaturePayne SRNational Interagency Confederation for Biological ResearchIntramural NIH HHSNational Cancer InstituteNIH1059-1066.e4https://www.ebi.ac.uk/biostudies/studies/S-EPMC6151150biostudies-literatureUnknown25(9)In response to environmental and other stresses, the σ⁵⁴ 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 σ⁵⁴ 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 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 σ⁵⁴ peptides capable of penetrating Gram-negative bacteria, binding the σ⁵⁴ promoter, and blocking the interaction bCell chemical biologyInhibition of Bacterial Gene Transcription with an RpoN-Based Stapled Peptide.PMC6151150ZIA BC011655Payne SRPau DIBoddy CNKim YJPharoah BMBernal FMoi CWhiting ALfalseInhibition of Bacterial Gene Transcription with an RpoN-Based Stapled Peptide.In response to environmental and other stresses, the σ⁵⁴ 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 σ⁵⁴ 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 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 σ⁵⁴ peptides capable of penetrating Gram-negative bacteria, binding the σ⁵⁴ promoter, and blocking the interaction b2018-01-01T00:00:00Z2018 Sep2026-05-03T03:01:12.473Z2019-09-26T07:00:32ZS-EPMC61511502988726510.1016/j.chembiol.2018.05.007