Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics.

ABSTRACT: Lipids play critical roles in cell biology, often through direct interactions with proteins. We recently described the use of photoreactive lipid probes combined with quantitative mass spectrometry to globally map lipid-protein interactions, and the effects of drugs on these interactions, in cells. Here, we investigate the broader potential of lipid-based chemical proteomic probes for determining the cellular targets of biologically active small molecules, including natural product derivatives and repurposed drugs of ill-defined mechanisms. We identify the prostaglandin-regulatory enzyme PTGR2 as a target of the antidiabetic hops derivative KDT501 and show that miconazole-an antifungal drug that attenuates disease severity in preclinical models of multiple sclerosis-inhibits SGPL1, an enzy

SUBMITTER: Lum KM 

PROVIDER: S-EPMC5650530 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature