Binding-based proteomic profiling and the fatty acid amides

Fatty acid amides represent a diverse and underappreciated family of lipids found in vertebrates and invertebrates. The most recognized, most studied, and best understood members of the fatty acid amide family are N-arachidonoylethanolamine (anandamide) and oleamide. Over 70 other fatty acid amides have been identified from biological systems and these non-anandamide and non-oleamide fatty acid amides are not well understood: their cellular functions, transport, biosynthesis, and degradation are, at best, partially elucidated. Most of the fatty acid amides are “orphan” ligands for “orphan” or unknown receptors. Interest in the fatty acid amides will wane without a more complete understanding of their function in vivo and most of these lipids will be mentioned in a few sentences in reviews on ananamide and/or olemide. In this commentary, we suggest that one strategy to dramatically increase our understanding of any member of the fatty acid amide family is the design, synthesis, and proper use of binding-based profiling probes (BBPPs) based on the structure of a specific fatty acid amide. A BBPP is an analog of a fatty acid amide that enables the controlled covalent attachment of the probe to a fatty acid amide-binding protein and, also, possesses a chemical moiety that will allow the purification and/or detection of the BBPP-labeled proteins. The identification of the proteins that specifically bind a fatty acid amide will foster a better understanding of the function, transport, and metabolism of a fatty acid amide.