Merkler David J, Leahy James W
Department of Chemistry, University of South Florida, Tampa, FL, USA.
Center for Drug Discovery and Innovation, University of South Florida, Tampa, FL USA.
Trends Res. 2018 Nov;1(4). doi: 10.15761/TR.1000120. Epub 2018 Nov 12.
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 -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 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.
脂肪酸酰胺是一类存在于脊椎动物和无脊椎动物中的脂质，种类多样但未得到充分重视。脂肪酸酰胺家族中最知名、研究最多且理解最深入的成员是花生四烯酸乙醇胺（阿南达胺）和油酰胺。从生物系统中已鉴定出70多种其他脂肪酸酰胺，而这些非阿南达胺和非油酰胺的脂肪酸酰胺尚未得到充分理解：它们的细胞功能、转运、生物合成和降解，充其量只是部分得到阐明。大多数脂肪酸酰胺是针对“孤儿”或未知受体的“孤儿”配体。如果不能更全面地了解其功能，对脂肪酸酰胺的兴趣将会减弱，并且在关于阿南达胺和/或油酰胺的综述中，大多数这些脂质只会被简单提及几句。在本评论中，我们认为，大幅增进我们对脂肪酸酰胺家族任何成员理解的一种策略是基于特定脂肪酸酰胺的结构设计、合成并合理使用基于结合的分析探针（BBPPs）。BBPP是脂肪酸酰胺的类似物，它能使探针可控地共价连接到脂肪酸酰胺结合蛋白上，并且还具有一个化学基团，可用于纯化和/或检测经BBPP标记的蛋白。鉴定与脂肪酸酰胺特异性结合的蛋白将有助于更好地理解脂肪酸酰胺的功能、转运和代谢。
