Inhibition of Bacterial Gene Transcription with an RpoN-Based Stapled Peptide.

ABSTRACT: In response to environmental and other stresses, the ?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 ?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 ?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 ?54 peptides capable of penetrating Gram-negative bacteria, binding the ?54 promoter, and blocking the interaction between endogenous ?54 and its target DNA sequence, thereby reducing transcription and activation of ?54 response genes.

SUBMITTER: Payne SR 

PROVIDER: S-EPMC6151150 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature