Puromycin inhibition of eucaryotic ribosomes. Differences in sensitivity between polypeptide synthesis directed by endogenous mRNA and synthetic templates including poly(U).
In a protein synthesis sytem derived from porcine uteri we have made the following observations: 1. Synthesis directed by the endogenous mRNA of the system is more sensitive to inhibition by puromycin than poly(U) directed synthesis. 2. Synthesis directed by the synthetic templates poly(G,U) and poly(C,U) is more sensitive to inhibition by puromycin than poly(U) directed synthesis and frequently shows a sensitivity to puromycin similar to that directed by endogenous mRNA. 3. Protein synthesis was inhibited by three aminoacyloligonucleotides (C-A-Phe, C-A-Asp, and C-A-Pro) which are analogs of the 3' terminus of aminoacyl tRNAs. Of the three, C-A-Phe was the most active and C-A-Asp the least active but, unlike puromycin, inhibition by these compounds was the same for endogenous and poly(U) directed synthesis. These results are interpreted as supporting the proposal that the acceptor site of ribosomes contains an hydrophobic binding region which interacts with the side chain of aliphatic amino acids, and particularly with the aromatic side chain of phenylalanine.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002474:Cell-Free System; D004305:Dose-Response Relationship, Drug; D005260:Female; D009843:Oligoribonucleotides / Q000494:pharmacology; D011072:Poly U / Q000378:metabolism; D011131:Polyribonucleotides / Q000378:metabolism; D014176:Protein Biosynthesis; D011691:Puromycin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013552:Swine; D013698:Templates, Genetic; D014599:Uterus / Q000378:metabolism*
D000596:Amino Acids; D009843:Oligoribonucleotides; D011131:Polyribonucleotides; D012333:RNA, Messenger; D011072:Poly U; D011691:Puromycin