The photochemical thiol-ene reaction as a versatile method for the synthesis of glutathioneS-conjugates targeting the bacterial potassium efflux system Kef.
The thiol-ene coupling reaction is emerging as an important conjugation reaction that is suitable for use in a biological setting. Here, we explore the utility of this reaction for the synthesis of glutathione-S-conjugates (GSX) and present a general, operationally simple, protocol with a wide substrate scope. The GSX afforded are an important class of compounds and provide invaluable molecular tools to study glutathione-binding proteins. In this study we apply the diverse library of GSX synthesised to further our understanding of the structural requirements for binding to the glutathione-binding protein, Kef, a bacterial K+efflux system, found in many bacterial pathogens. This system is vital to the survival of bacteria upon exposure to electrophiles, and plays an essential role in the maintenance of intracellular pH and K+homeostasis. Consequently, Kef is an appealing target for the development of novel antibacterial drugs.
Department of Chemistry , Chemistry Research Laboratory , University of Oxford , Mansfield Road , Oxford , OX1 3TA , UK . Email: stuart.conway@chem.ox.ac.uk ; Email: jess.healy@ucl.ac.uk; Department of Pharmaceutical and Biological Chemistry , UCL School of Pharmacy , University College London , 29/39 Brunswick Square , WC1N, 1AX , UK.
Jess
J
Healy
Institute of Medical Sciences , University of Aberdeen , Foresterhill , Aberdeen , AB25 2ZD , UK.
Tim
T
Rasmussen
Institute of Medical Sciences , University of Aberdeen , Foresterhill , Aberdeen , AB25 2ZD , UK.
Samantha
S
Miller
Institute of Medical Sciences , University of Aberdeen , Foresterhill , Aberdeen , AB25 2ZD , UK.
Ian R
IR
Booth
Department of Chemistry , Chemistry Research Laboratory , University of Oxford , Mansfield Road , Oxford , OX1 3TA , UK . Email: stuart.conway@chem.ox.ac.uk ; Email: jess.healy@ucl.ac.uk.
Stuart J
SJ
Conway