N-Alkoxysulfamide, N-hydroxysulfamide, and sulfamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
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.
Lee
Jeewoo
J
Laboratory of Medicinal Chemistry, RIPS, College of Pharmacy, Seoul National University, Seoul 151-742, South Korea.
Kim
Sung Eun
SE
Lee
Ji Young
JY
Kim
Su Yeon
SY
Kang
Sang Uk
SU
Seo
Seung Hwan
SH
Chun
Moon Woo
MW
Kang
Taehee
T
Choi
Soo Young
SY
Kim
Hea Ok
HO
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
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D013449:Sulfonamides; D013451:Sulfonic Acids; D008718:Methionine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase