Ester and hydroxamate analogues of methionyl and isoleucyl adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases

The structure–activity relationship on a series of ester and hydroxamate analogues of methionyl and isoleucyl adenylate has been investigated through introducing linkers between the 1′-position of ribose and adenine surrogates as methionyl-tRNA, and isoleucyl-tRNA synthetase inhibitors, respectively. The results indicate that ester analogue 23 was found to be a potent inhibitor of Escherichia coli methionyl-tRNA synthetase, and its interaction with the active site was proposed by a molecular modeling study.