Author/Authors :
Carl P. Decicco، نويسنده , , David J. Nelson، نويسنده , , Ying Luo، نويسنده , , Li Shen، نويسنده , , Kurumi Y. Horiuchi، نويسنده , , Karen M. Amsler، نويسنده , , Lorie A. Foster، نويسنده , , Susan M. Spitz، نويسنده , , Jayson J. Merrill، نويسنده , , Christine F. Sizemore، نويسنده , , Kelley C. Rogers، نويسنده , , Robert A. Copeland، نويسنده , , Mark R. Harpel، نويسنده ,
Abstract :
Analogues of glutamyl-γ-boronate (1) were synthesized as mechanism-based inhibitors of bacterial Glu-tRNAGln 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.
