An active puromycin analog derived from a non nephrotoxic aminonucleoside

Replacement of the 5' OH group of puromycin aminonucleoside (PAN) with H resulted in the elimination of kidney toxicity associated with administration of PAN. Thus, 5' deoxy PAN was not nephrotoxic to rats under the usual criteria. The corresponding 5' deoxypuromycin derived from 5' deoxy PAN was examined in a ribosomal peptidyl transferase assay and was found to be an excellent substrate for the transpeptidation reaction with bacterial ribosomes; the Km was 0.29 mM compared to the Km for puromycin of 0.20 mM. Thus, a puromycin analog has been prepared which retains puromycin like activity at the ribosomal level, but which is capable of releasing only a non nephrotoxic aminonucleoside by enzymatic hydrolysis of the p methoxyphenylalanyl side chain.