[摘要]：The aminoacyl-tRNA synthetase family of enzymes is the target of many antibacterials and inhibitors of eukaryotic hyperproliferation. In screening analogs of 5'-O-(N-L-aminoacyl)-sulfamoyladenosine contg. all 20 proteinogenic amino acids, we found these compds. to have potent immunosuppressive activity. Also, we found that combinations of these compds. inhibited the immune response synergistically. Based on these data, analogs with modifications at the aminoacyl and ribose moieties were designed and evaluated, and several of these showed high immunosuppressive potency, with I having an IC50 of 80 nM, when tested in a cellular mixed lymphocyte reaction assay. Apart from showing the potential of aminoacyl-tRNA synthetase inhibitors as immunosuppressants, the current study also provides arguments for careful evaluation of the immunosuppressive activity of developmental antibacterials that target these enzymes.
