Lactate
pump proteins in human liver cells are new, exciting and “un-drugged” targets
for medicinal chemistry. To identify inhibitors of the pump, we need an assay
for pump activity. There are important advantages to having fluorescence
assays. Fluorescence assays are very sensitive, so this allows identification
of even weak inhibitors. Our idea is to use reactive lactate analogs that will
pass through the pump. Once inside the cell,they will react with
phosphine-based probes to generate a fluorescent signal.
As lactate analogs, we will first use 3-azidolactate. It is known that azide inside cells react selectively with phosphines.The reaction between the azide and the phosphine first makes a phosphinimine and N2. The phosphinimine hydrolyzes rapidly to the amine and phosphine oxide.
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