title: Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
abstract: As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phenolic analogues containing bioisosteric linkers mimicking ribose have been investigated. Inhibition of synthesized compounds to the aminoacylation reaction by the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tRNA synthetases indicated that 18 was found to be a potent inhibitor of isoleucyl-tRNA synthetase. A molecular modeling study demonstrated that in 18, isovanillate and hydroxamate served as proper surrogates for adenine and ribose in isoleucyl adenylate, respectively.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Kwanak-Ku, South Korea. jeewoo@snu.ac.kr
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: S U
authors.initials: SU
authors.lastname: Kang
authors.forename: S Y
authors.initials: SY
authors.lastname: Kim
authors.forename: S E
authors.initials: SE
authors.lastname: Kim
authors.forename: Y J
authors.initials: YJ
authors.lastname: Job
authors.forename: S
authors.initials: S
authors.lastname: Kim
mesh_terms: D000225:Adenine / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006877:Hydroxamic Acids / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007532:Isoleucine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D007533:Isoleucine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008715:Methionine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D008718:Methionine-tRNA Ligase / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D012266:Ribose / Q000737:chemistry; D014641:Vanillic Acid / Q000031:analogs & derivatives*
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D007532:Isoleucine; D012266:Ribose; D008715:Methionine; D008718:Methionine-tRNA Ligase; D007533:Isoleucine-tRNA Ligase; D014641:Vanillic Acid; D000225:Adenine