biostudies-literatureHoglinger DHHS | National Institutes of HealthEuropean Commission Directorate-General for Research and InnovationDeutsche Forschungsgemeinschaft1566-1571https://www.ebi.ac.uk/biostudies/studies/S-EPMC5320957biostudies-literatureUnknown114(7)Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid-protein interactions, and intracellular lipid localization with a single tool per target lipid. The probes are equipped with two photoreactive groups to allow photoliberation (uncaging) and photo-cross-linking in a sequential manner, as well as a click-handle for subsequent functionalization. We demonstrate the versatility of the design for the signaling lipids sphingosine and diacylglycerol; uncaging of the probe for these two species triggered calcium signaling and intracellular protein translocationProceedings of the National Academy of Sciences of the United States of AmericaTrifunctional lipid probes for comprehensive studies of single lipid species in living cells.PMC5320957NICHD Intramural Research Programme289278229597Transregio 83Hauke SPorter FDSchultz CHaberkant PHoglinger DNadler AStein FKirkpatrick JSchifferer MfalseTrifunctional lipid probes for comprehensive studies of single lipid species in living cells.Lipid-mediated signaling events regulate many cellular processes. Investigations of the complex underlying mechanisms are difficult because several different methods need to be used under varying conditions. Here we introduce multifunctional lipid derivatives to study lipid metabolism, lipid-protein interactions, and intracellular lipid localization with a single tool per target lipid. The probes are equipped with two photoreactive groups to allow photoliberation (uncaging) and photo-cross-linking in a sequential manner, as well as a click-handle for subsequent functionalization. We demonstrate the versatility of the design for the signaling lipids sphingosine and diacylglycerol; uncaging of the probe for these two species triggered calcium signaling and intracellular protein translocation2017-01-01T00:00:00Z2017 Feb2025-04-22T19:24:47.397Z2019-03-27T02:37:05ZS-EPMC53209572815413010.1073/pnas.1611096114