Glutamyl-γ-boronate Inhibitors of Bacterial Glu-tRNAGln Amidotransferase

Abstract Analogues of glutamyl-γ-boronate ( 1 ) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNA Gln amidotransferase (Glu-AdT) and were designed to engage a putative catalytic serine nucleophile required for the glutaminase activity of the enzyme. Although 1 provides potent enzyme inhibition, structure–activity studies revealed a narrow range of tolerated chemical changes that maintained activity. Nonetheless, growth inhibition of organisms that require Glu-AdT by the most potent enzyme inhibitors appears to validate mechanism-based inhibitor design of Glu-AdT as an approach to antimicrobial development.