Michel Benoît Y, Krishnakumar Kollappillil S, Johansson Magnus, Ehrenberg Måns, Strazewski Peter
Laboratoire de Synthèse de Biomolécules, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (UMR 5246), Université Claude Bernard, Lyon 1, France.
Nucleic Acids Symp Ser (Oxf). 2008(52):33-4. doi: 10.1093/nass/nrn017.
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.
如果设计得当，能够结合核糖体受体位点并接管新生肽的氨酰基核糖核苷类似物具有抗生素和细胞抑制活性的潜力。在此，我们展示了一项关于天然和合成肽受体的内在构象及其肽接受氨基碱性的研究。通过从头算计算以及温度和pH依赖性的¹H NMR实验，阐明了几种合成嘌呤霉素类似物的构象和热力学参数。通过¹H NMR测定了其肽接受氨基的内在碱性，并与具有相同氨基酸侧链的氨酰基转移RNA的肽接受氨基的有效碱性进行了比较，后者是根据mRNA编程核糖体肽基转移的pH依赖性动力学估算得出的。
