Structural and functional prerequisites for ribosomal nascent peptide acceptors: attempts to decipher the nature of the ribosome's catalysis of peptide bond formation.
Aminoacyl ribonucleoside analogues that are capable of binding to the acceptor site of ribosomes and taking over the nascent peptide bear, if properly designed, the potential of antibiotic and cytostatic activity. Here we present a study on the intrinsic conformations of natural and synthetic peptide acceptors and the basicities of their peptide accepting amino groups. The conformations and thermodynamic parameters of several synthetic puromycin analogues have been elucidated through ab initio calculations as well as temperature and pH dependent (1)H NMR experiments. The intrinsic basicities of their peptide accepting amino groups were determined through (1)H NMR and compared to the effective basicities of the peptide accepting amino groups of aminoacyl transfer RNAs with the same amino acid side chains, as estimated from the pH dependent kinetics of mRNA programmed ribosomal peptidyl transfer.
Michel
Benoît Y
BY
Laboratoire de Synthèse de Biomolécules, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (UMR 5246), Université Claude Bernard, Lyon 1, France.
Krishnakumar
Kollappillil S
KS
Johansson
Magnus
M
Ehrenberg
Måns
M
Strazewski
Peter
P
D002384:Catalysis; D007700:Kinetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010441:Peptide Chain Elongation, Translational; D010455:Peptides / Q000737:chemistry*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry*; D011691:Puromycin / Q000031:analogs & derivatives* / Q000737:chemistry; D012345:RNA, Transfer, Amino Acid-Specific / Q000737:chemistry; D012270:Ribosomes / Q000737:chemistry*; D013816:Thermodynamics
D010455:Peptides; D011500:Protein Synthesis Inhibitors; D012345:RNA, Transfer, Amino Acid-Specific; D011691:Puromycin