Structural and functional prerequisites for ribosomal nascentpeptide acceptors: Attempts to decipher the nature of the ribosome's catalysis of peptide bond formation

Abstract Aminoacyl ribonucleoside analogues that are capable of binding to the acceptor site of ribosomes and taking over the nascent peptide bear, if properly designed, thepotential of antibiotic and cytostatic activity. Here wepresent 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 intio calculations as well as temperature and pH dependent 1H NMR experiments. The intrinsic basicities of their peptide accepting amino groups were determined through 1H NMR and compared to the effective basici-ties 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 mRNAprogrammed ribosomal peptidyl transfer.