title: N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
abstract: A series of sulfamate surrogates of methionyl and isoleucyl adenylate have been investigated as MetRS and IleRS inhibitors by modifications of the sulfamate linker and adenine moieties. The discovery of 2-iodo Ile-NHSO(2)-AMP (58) as a potent Escherichia coli IleRS inhibitor revealed that a significant hydrophobic interaction between the 2-substituent of Ile-NHSO(2)-AMP and the adenine binding site of IleRS provided its high potency to the enzyme.
authors.affiliation: Laboratory of Medicinal Chemistry, RIPS, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jeewoo
authors.initials: J
authors.lastname: Lee
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Lee
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Kim
authors.forename: Sang Uk
authors.initials: SU
authors.lastname: Kang
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Seo
authors.forename: Moon Woo
authors.initials: MW
authors.lastname: Chun
authors.forename: Taehee
authors.initials: T
authors.lastname: Kang
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
mesh_terms: D001665:Binding Sites; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D007202:Indicators and Reagents; D007533:Isoleucine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D016963:Thermus thermophilus / Q000201:enzymology
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D013449:Sulfonamides; D013451:Sulfonic Acids; D008718:Methionine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase