2-Oxoglutarate derivatives can selectively enhance or inhibit the activity of human oxygenases

Abstract2-Oxoglutarate (2OG) oxygenases are validated agrochemical and human drug targets. The potential for modulating their activity with 2OG derivatives has not been explored, possibly due to concerns regarding selectivity. We report proof-of-principle studies demonstrating selective enhancement or inhibition of 2OG oxygenase activity by 2-oxo acids. The human 2OG oxygenases studied, factor inhibiting hypoxia-inducible transcription factor HIF-α (FIH) and aspartate/asparagine-β-hydroxylase (AspH), catalyze C3 hydroxylations of Asp/Asn-residues. Of 35 tested 2OG derivatives, 10 enhance and 17 inhibit FIH activity. Comparison with results for AspH reveals that 2OG derivatives selectively enhance or inhibit FIH or AspH. Comparison of FIH structures complexed with 2OG derivatives to those for AspH provides insight into the basis of the observed selectivity. 2-Oxo acid derivatives have potential as drugs, for use in biomimetic catalysis, and in functional studies. The results suggest that the in vivo activity of 2OG oxygenases may be regulated by natural 2-oxo acids other than 2OG.

Bioinspired chemistry at MOF secondary building units

This perspective describes recent developments and future directions in bioinorganic chemistry and biomimetic catalysis centered at metal–organic framework secondary building units.

A series of highly stable porphyrinic metal–organic frameworks based on iron–oxo chain clusters: design, synthesis and biomimetic catalysis

A facile synthesis of a series of Fe–oxo chain-based porphyrinic MOFs (namely M-PMOF-3(Fe), M = Fe, Co, Ni, Cu) has been reported.