Inhibition of peptidyltransferase and possible mode of action of a dipeptidyl chloramphenicol analog.
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.
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D001665:Binding Sites; D002701:Chloramphenicol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004926:Escherichia coli / Q000201:enzymology*; D007700:Kinetics; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors*; D011691:Puromycin / Q000494:pharmacology; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012270:Ribosomes / Q000201:enzymology; D013329:Structure-Activity Relationship
D012346:RNA, Transfer, Amino Acyl; D011691:Puromycin; D002701:Chloramphenicol; C042095:2-(phenylalanylglycyl)amino-3-(4-nitrophenyl)-1,3-propanediol; D000217:Acyltransferases; D010458:Peptidyl Transferases