Puromycin analogs. Effect of aryl-substituted puromycin analogs on the ribosomal peptidyltransferase reaction

Abstract

A series of o- and p-substituted L-phenylalanylpuromycin analogs [antineoplastic drugs] were synthesized and evaluated as substrates for the peptidyltransferase reaction of Escherichia coli ribosomes. Kinetic results reveal that substitution of the p-methoxy group of the puromycin molecule alters the peptidyltransferase activity of the molecule with the following decreasing order of substrate efficiencies: p-NH2 > p-NHCOCH3 > p-NO2 = p-NHCO(CH2)2CH3 > p-NHCOCH2Br. The inability of the ribosome to tolerate a nitro group at the ortho position of the phenylalanine ring precluded the use of the photosensitive puromycin analog 2-nitro-4-azidophenylalanylpuromycin aminonucleoside as a photoaffinity label for the peptidyltransferase site.