Synthesis of charged receptors selective for anionic components of bacterial membranes

Abstract

A receptor able to selectively bind a phosphatidylglycerol head group of a bacterial membrane phospholipid, PPG is an attractive synthetic target as a modular component of an antimicrobial therapeutic. The major challenge to the preparation of such receptors, able to exclusively recognize this bacterial membrane component, is to create a binding motif that will complex a phosphorus anion, along with hydroxyl functionality, strongly and selectively in an aqueous environment. This study reports the synthesis and characterization of two families of charged hydrogen-bonding receptors. The first family of receptors contains different binding pocket sizes to accommodate the phosphate head group of the PPG anion while the second family of receptors contains multiple binding domains for the said phosphate head group and the glycerol hydroxyl functionality from the PPG. Following the synthesis and purification, the receptors were subjected to binding studies with inorganic dihydrogenphosphate anions and phosphatidylglycerol anions monitored with both proton NMR spectroscopy and isothermal titration calorimetry to reveal the binding stoichiometry and binding thermodynamics between each receptor and the anion.