Effects on LuxR-Regulated Bioluminescence of Cyclodextrin-Acyl-L-Homoserine Lactone Hybrids

Abstract

In this work, acyl homoserine lactones (AHLs) are grafted, the most studied signaling molecules in many Gram-negative bacteria, onto cyclodextrins (CDs) by copper-catalyzed azide–alkyne cycloaddition “click” coupling between alkynyl-AHLs and 6-azido-CDs derived from α- and β-CD, native or methylated. Attaching biomolecules onto a CD scaffold is a known strategy to enhance their properties, but designing CD-AHL conjugates has never been reported. These molecules were fully characterized by NMR and high-resolution mass spectrometry, and the study of their solubility and conformation reveals significant conformational changes due to the presence of the AHL appendage on the CD structure. One of the hybrids (per-AHL-β-CD, 9_B) exhibits higher solubility in water than AHL and β-CD alone. The new CD-AHLs conjugates are found to modulate bioluminescence in a quorum Sensing LuxR-regulated light-producing bacterial model, with significant variations depending on the structure. The per-AHL-β-CD, 9_B, is found to be the most active compound in the series.