A dipeptidyl chloramphenicol analog, D-threo-2-(L-phenylalanylglycyl)amino-3-p-nitrophenyl-1,3-propanediol, has been prepared and examined as an inhibitor of ribosomal peptidyltransferase. The analog is a more effective inhibitor of poly (U,C) directed protein biosynthesis in an Escherichia coli cell-free system than chloramphenicol and shows inhibitory activity equal to the parent antibiotic in the transpeptidation reaction. These results and the common structural features of puromycin and this compound suggest a model for the binding modes of chloramphenicol and chloramphenicol analogs. This proposal invokes four major binding pockets at the A-site of the peptidyltransferase center.
|Original language||English (US)|
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Jul 31 1984|
Bibliographical noteFunding Information:
We thank Jay Br ownell for assistance in the biological assays. This investigation was supported by Grants CA 13592 and CA 23263 from the National Cancer Institute, Department of Health, Education, and Welfare.