Issue 30, 2022

A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity

Abstract

Lipids fulfill a variety of important physiological functions, such as energy storage, providing a hydrophobic barrier, and signal transduction. Despite this plethora of biological roles, lipids are rarely considered a potential target for medical applications. Here, we report a set of neutral small molecules that contain boronic acid and urea functionalities to selectively recognize the bacterial lipid phosphatidylglycerol (PG). The affinity and selectivity was determined using 1H NMR titrations and a liposome-based Alizarin Red S assay. Minimum inhibitory concentrations (MIC) were determined to assess antibacterial activity. The most potent compounds display an association constant with PG in liposomes of at least 5 × 103 M−1, function as antibacterial agents against Gram-positive bacteria (MIC = 12.5–25 μM), and show little hemolytic activity. Mode of action studies suggest that the boronic acids bind to the headgroup of the PG lipids, which leads to a change in membrane fluidity and ultimately causes membrane depolarization and cell death.

Graphical abstract: A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity

Supplementary files

Article information

Article type
Paper
Submitted
23 nov 2021
Accepted
15 dec 2021
First published
16 dec 2021

Org. Biomol. Chem., 2022,20, 5958-5966

A supramolecular host for phosphatidylglycerol (PG) lipids with antibacterial activity

E. S. Williams, H. Gneid, S. R. Marshall, M. J. González, J. A. Mandelbaum and N. Busschaert, Org. Biomol. Chem., 2022, 20, 5958 DOI: 10.1039/D1OB02298A

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