Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases.
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.
Lee
J
J
Laboratory of Medicinal Chemistry, College of Pharmacy, Seoul National University, Kwanak-Ku, South Korea. jeewoo@snu.ac.kr
Kang
S U
SU
Kim
S Y
SY
Kim
S E
SE
Job
Y J
YJ
Kim
S
S
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*
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