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.
Bibliographical noteFunding Information:
This work was supported in part by a grant (HMP-00-CH-15-0014) from the Ministry of Health & Welfare and by the Brain Korea 21 Project to J. Lee, as well as a grant from the National Creative Research Initiatives from Ministry of Science and Technology to S. Kim.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry