TY - JOUR
T1 - Easily Accessible, Highly Potent, Photocontrolled Modulators of Bacterial Communication
AU - Hansen, Mickel
AU - Hille, Jacques
AU - Szymanski, Wiktor
AU - Driessen, Arnold
AU - Feringa, B.L.
PY - 2019/4/15
Y1 - 2019/4/15
N2 - External control of bacterial communication—quorum sensing—allows for the
regulation of a multitude of biological processes. Herein, we describe the development of a new synthetic methodology, as well as the characterization, photoisomerization, and biological evaluation of a privileged series of novel photoswitchable quorum-sensing agonists and antagonists. The presented method allows for the rapid and convenient synthesis of previously unknown photoswitchable agonists with up to 70% quorum-sensing induction and inhibitors reaching up to 40% inhibition, which significantly extends the level of photocontrol over bacterial communication achieved before. Remarkably, for the lead photoswitchable agonist, a >700-fold difference in activity was observed between the irradiated and non-irradiated forms, which allows for antagonism to -agonism switching upon exposure to light, showing levels of control unprecedented in photopharmacology. Finally, utilizing this system, we were able to regulate toxin production in Pseudomonas aeruginosa with light.
AB - External control of bacterial communication—quorum sensing—allows for the
regulation of a multitude of biological processes. Herein, we describe the development of a new synthetic methodology, as well as the characterization, photoisomerization, and biological evaluation of a privileged series of novel photoswitchable quorum-sensing agonists and antagonists. The presented method allows for the rapid and convenient synthesis of previously unknown photoswitchable agonists with up to 70% quorum-sensing induction and inhibitors reaching up to 40% inhibition, which significantly extends the level of photocontrol over bacterial communication achieved before. Remarkably, for the lead photoswitchable agonist, a >700-fold difference in activity was observed between the irradiated and non-irradiated forms, which allows for antagonism to -agonism switching upon exposure to light, showing levels of control unprecedented in photopharmacology. Finally, utilizing this system, we were able to regulate toxin production in Pseudomonas aeruginosa with light.
U2 - 10.1016/j.chempr.2019.03.005
DO - 10.1016/j.chempr.2019.03.005
M3 - Article
VL - 5
SP - 1293
EP - 1301
JO - Chem
JF - Chem
SN - 2451-9294
IS - 5
ER -