Synthesis and application of a photocaged L-lactate

Abstract

L-Lactate, once considered a metabolic waste product of glycolysis, is now recognized as a vitally important metabolite and signaling molecule in multiple biological pathways. However, exploring L-lactate's emerging intra- and extra-cellular roles is hindered by a lack of tools to locally perturb L-lactate concentration intracellularly and extracellularly. Photocaged compounds are a powerful way to introduce bioactive molecules with spatial and temporal precision using illumination. Here, we report the development of a photocaged derivative of L- lactate, 4-methoxy-7-nitroindolinyl L-lactate (MNI-L-lac), that releases L-lactate upon UV illumination. We validated MNI-L-lac in cell culture by demonstrating that the photorelease of L-lactate elicits a response from genetically encoded extra- and intracellular L-lactate biosensors. These results indicate that MNI-L-lac may be useful for perturbing the concentration of endogenous L-lactate in order to investigate L-lactate's roles in metabolism and signaling pathways.