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.
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.
