title: The puromycin route to assess stereo- and regiochemical constraints on peptide bond formation in eukaryotic ribosomes.
abstract: We synthesized a series of puromycin analogues to probe the chemical specificity of the ribosome in an intact eukaryotic translation system. These studies reveal that both d-enantiomers and beta-amino acid analogues can be incorporated into protein, and provide a quantitative means to rank natural and unnatural residues. Modeling of a d-amino acid analogue into the 50S ribosomal subunit indicates that steric clash may provide part of the chiral discrimination. The data presented provide one metric of the chiral and regiospecificity of mammalian ribosomes.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Starck
authors.forename: Xin
authors.initials: X
authors.lastname: Qi
authors.forename: Brett N
authors.initials: BN
authors.lastname: Olsen
authors.forename: Richard W
authors.initials: RW
authors.lastname: Roberts
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000494:pharmacology; D011506:Proteins / Q000235:genetics; D011691:Puromycin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D011691:Puromycin; D005914:Globins