Synthesis and application of a photocaged L-lactate

Abstract

O_SCPLOWLC_SCPLOW-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 O_SCPLOWLC_SCPLOW-lactates emerging intra- and extra-cellular roles is hindered by a lack of tools to locally perturb O_SCPLOWLC_SCPLOW-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 O_SCPLOWLC_SCPLOW-lactate, 4-methoxy-7-nitroindolinyl O_SCPLOWLC_SCPLOW-lactate (MNI-O_SCPLOWLC_SCPLOW-lac), that releases O_SCPLOWLC_SCPLOW-lactate upon UV illumination. We validated MNI-O_SCPLOWLC_SCPLOW-lac in cell culture by demonstrating that the photorelease of O_SCPLOWLC_SCPLOW-lactate elicits a response from genetically encoded extra- and intracellular O_SCPLOWLC_SCPLOW-lactate biosensors. These results indicate that MNI-O_SCPLOWLC_SCPLOW-lac may be useful for perturbing the concentration of endogenous O_SCPLOWLC_SCPLOW-lactate in order to investigate O_SCPLOWLC_SCPLOW-lactates roles in metabolism and signaling pathways.