Event Title

Synthesis of Fluorescent Quinolone Inhibitors of the ²-Barrel Assembly Machine

Mentor 1

Alan Schwabacher

Location

Union Wisconsin Room

Start Date

29-4-2016 1:30 PM

End Date

29-4-2016 3:30 PM

Description

Much of antibiotic resistance results from membrane proteins that, through the process of active transport, remove antibiotics from within the membrane to outside the membrane, rendering said antibiotics useless. Many membrane proteins called efflux protein complexes responsible for this are, in part, folded by a different protein-complex called the β-barrel assembly machine (BAM). The secondary structure of proteins folded by this machine is of the form of a β-barrel, composed of β-pleated sheets. Currently, a rigid aminoquinolone structure with strategic hydrogen-bonding sites is being pursued as a molecular template that will hydrogen-bond small peptides by mimicking the interactions in a β-sheet. These templates will be used to study intramolecular forces in β-sheets and β-barrels. Inhibition of the β-barrel assembly machine, killing gram-negative bacteria with high efficacy, has been shown with particular short peptides. However, these peptides make poor drug possibilities due to the inherently poor quality of being metabolized by the patient to which these drugs may be given, as they would be digested like other proteins. Therefore, we propose possible inhibition of the β-barrel assembly machine via our synthetic molecule mimicking the interactions of that peptide which has been shown to kill gram-negative bacteria in proper dosages.

This document is currently not available here.

Share

COinS
 
Apr 29th, 1:30 PM Apr 29th, 3:30 PM

Synthesis of Fluorescent Quinolone Inhibitors of the ²-Barrel Assembly Machine

Union Wisconsin Room

Much of antibiotic resistance results from membrane proteins that, through the process of active transport, remove antibiotics from within the membrane to outside the membrane, rendering said antibiotics useless. Many membrane proteins called efflux protein complexes responsible for this are, in part, folded by a different protein-complex called the β-barrel assembly machine (BAM). The secondary structure of proteins folded by this machine is of the form of a β-barrel, composed of β-pleated sheets. Currently, a rigid aminoquinolone structure with strategic hydrogen-bonding sites is being pursued as a molecular template that will hydrogen-bond small peptides by mimicking the interactions in a β-sheet. These templates will be used to study intramolecular forces in β-sheets and β-barrels. Inhibition of the β-barrel assembly machine, killing gram-negative bacteria with high efficacy, has been shown with particular short peptides. However, these peptides make poor drug possibilities due to the inherently poor quality of being metabolized by the patient to which these drugs may be given, as they would be digested like other proteins. Therefore, we propose possible inhibition of the β-barrel assembly machine via our synthetic molecule mimicking the interactions of that peptide which has been shown to kill gram-negative bacteria in proper dosages.