Discovery of Trypanosoma brucei inhibitors enabled by a unified synthesis of diverse sulfonyl fluorides.

Sets of electrophilic probes are generally prepared using a narrow toolkit of robust reactions, which tends to limit both their structural and functional diversity. A unified synthesis of skeletally-diverse sulfonyl fluorides was developed that relied upon photoredox-catalysed dehydrogenative couplings between hetaryl sulfonyl fluorides and hydrogen donor building blocks. A set of 32 diverse probes was prepared, and then screened against Trypanosoma brucei.

A fluorescent photoaffinity probe for formyl peptide receptor 1 labelling in living cells.

Fluorescent ligands for G-protein coupled receptors (GPCRs) are valuable tools for studying the expression, pharmacology and modulation of these therapeutically important proteins in living cells. Here we report a fluorescent photoaffinity probe for Formyl peptide receptor 1 (FPR1), a critical component of the innate immune response to bacterial infection and a promising target in inflammatory diseases. We demonstrate that the probe binds and covalently crosslinks to FPR1 with good specificity at nanomolar concentrations in living cells and is a useful tool for visualisation and characterisation of this receptor.

Pseudomonas aeruginosa utilizes the host-derived polyamine spermidine to facilitate antimicrobial tolerance.

Pseudomonas aeruginosa undergoes diversification during infection of the cystic fibrosis (CF) lung. Understanding these changes requires model systems that capture the complexity of the CF lung environment. We previously identified loss-of-function mutations in the 2-component regulatory system sensor kinase gene pmrB in P.