Bacterial infections caused by antibiotic resistant bacteria have been on the rise in recent years.  In order to combat this phenomenon, new types of antibiotics are needed, especially new types of antibiotics that have novel modes of action in killing bacterial cells.  Certain bacteria possess toxin/antitoxin systems that could be exploited as new targets for antibiotic drugs.  These toxin/antitoxin systems feature a tight binding interaction between a protein that is toxic to the cell in its free form, but is rendered inert when bound to the antitoxin protein.  An example of a toxin/anti-toxin system is the MazE/MazF complex found in Escherichia Coli.  In this system, MazF is a ribonuclease that is toxic to the cell unless it is bound to MazE (the antitoxin). A pentapeptide capable of inhibiting the MaE/F interaction and causing bacterial cell death has recently been discovered.  It is postulated that molecules with similar properties may also be able to inhibit the MazE/F interaction in E. Coli.  To test this hypothesis, different peptides and peptidomimetics that are similar to the original pentapeptide were synthesized.  These peptides were designed to probe the stereochemical and steric promiscuity of the MazE/F interaction.  These products were then assayed for their ability to trigger apoptosis in E. Coli via MazE/F inhibition.

Probing the stereochemical and steric promiscuity of MazE/F inhibitors

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.