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

Author:

Payne, Sterling R

Pau, Daniel I

Whiting, Amanda L

Kim, Ye Joon

Pharoah, Blaze M

Moi, Christina

Boddy, Christopher N

Bernal, Federico
Author Address

Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA., Department of Chemistry and Biomolecular Sciences, University of Ottawa, Ottawa, ON K1N 6N5, Canada., Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA. Electronic address: bernalf@mail.nih.gov.,

Abstract:

In response to environmental and other stresses, the s54 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 s54 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 s54, 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 s54 peptides capable of penetrating Gram-negative bacteria, binding the s54 promoter, and blocking the interaction between endogenous s54 and its target DNA sequence, thereby reducing transcription and activation of s54 response genes. Published by Elsevier Ltd.

See More

Author Address