Mimicking the 2-oxoglutaric acid signalling function using molecular probes: insights from structural and functional investigations

• Published in: Organic & biomolecular chemistry 2014-07, Vol.12 (26), p.4723-4729
• Main Authors: Wang, Yang, Liu, Xinjun, Laurini, Erik, Posocco, Paola, Ziarelli, Fabio, Fermeglia, Maurizio, Qu, Fanqi, Pricl, Sabrina, Zhang, Cheng-Cai, Peng, Ling
• Format: Article
• Language: English
• Subjects: Anabaena - metabolism; DNA - metabolism; Ketoglutaric Acids - metabolism; Molecular Dynamics Simulation; Molecular Probes - chemical synthesis; Molecular Probes - chemistry; Molecular Probes - metabolism; Proton Magnetic Resonance Spectroscopy; Signal Transduction; Structure-Activity Relationship; Thermodynamics; Transcription Factors - metabolism
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c4ob00630e

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.