Synthesis and application of a photocaged L-lactate

Abstract

Abstractl-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, exploringl-lactate’s emerging intra- and extra-cellular roles is hindered by a lack of tools to locally perturbl-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 ofl-lactate, 4-methoxy-7-nitroindolinyll-lactate (MNI-l-lac), that releasesl-lactate upon UV illumination. We validated MNI-l-lac in cell culture by demonstrating that the photorelease ofl-lactate elicits a response from genetically encoded extra- and intracellularl-lactate biosensors. These results indicate that MNI-l-lac may be useful for perturbing the concentration of endogenousl-lactate in order to investigatel-lactate’s roles in metabolism and signaling pathways.