Vanilloid and isovanilloid analogues as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

As aminoacyl adenylate surrogates, a series of methionyl and isoleucyl phen olic analogues containing bioisosteric linkers mimicking ribose have been i nvestigated. Inhibition of synthesized compounds to the aminoacylation reac tion b?i the corresponding Escherichia coli methionyl-tRNA and isoleucyl-tR NA synthetases indicated that 18 was found to be a potent inhibitor of isol eucyl-tRNA synthetase. A molecular modeling study demonstrated that in 18. isovanillate and hydroxamate served as proper surrogates for adenine and ri bose in isoleucyl adenylate, respectively. (C) 2001 Elsevier Science Ltd. A ll rights reserved.