2-Oxoglutaric acid (2-OG) has gained considerable attention because of its newly discovered signalling role in addition to its established metabolic functions. With the aim of further exploring the signalling function of 2-OG, here we present a structure-activity relationship study using 2-OG probes bearing different carbon chain lengths and terminal groups. Our results highlight the importance of the five-membered carbon molecular skeleton and of the two carboxylic terminals in maintaining the signalling functions of the parent molecule 2-OG. These findings provide valuable information for designing new, effective molecular probes able to dissect and discriminate the newly discovered, complex signalling role of 2-OG from its canonical activity in metabolism.
