title: Synthesis of 3'-fluoro-tRNA analogues for exploring non-ribosomal peptide synthesis in bacteria.
abstract: Aminoacyl-tRNAs (aa-tRNAs) participate in a vast repertoire of metabolic pathways, including the synthesis of the peptidoglycan network in the cell walls of bacterial pathogens. Synthesis of aminoacyl-tRNA analogues is critical for further understanding the mechanisms of these reactions. Here we report the semi-synthesis of 3'-fluoro analogues of Ala-tRNA(Ala) . The presence of fluorine in the 3'-position blocks Ala at the 2'-position by preventing spontaneous migration of the residue between positions 2' and 3'. NMR analyses showed that substitution of the 3'-hydroxy group by fluorine in the ribo configuration favours the S-type conformation of the furanose ring of terminal adenosine A76. In contrast, the N-type conformation is favoured by the presence of fluorine in the xylo configuration. Thus, introduction of fluorine in the ribo and xylo configurations affects the conformation of the furanose ring in reciprocal ways. These compounds should provide insight into substrate recognition by Fem transferases and the Ala-tRNA synthetases.
authors.affiliation: Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques, Team CBNIT, Université Paris Descartes, CNRS UMR 8601, 75006 Paris (France).
authors.forename: Laura
authors.initials: L
authors.lastname: Iannazzo
authors.forename: Guillaume
authors.initials: G
authors.lastname: Laisné
authors.forename: Matthieu
authors.initials: M
authors.lastname: Fonvielle
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Braud
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Herbeuval
authors.forename: Michel
authors.initials: M
authors.lastname: Arthur
authors.forename: Mélanie
authors.initials: M
authors.lastname: Etheve-Quelquejeu
mesh_terms: D001671:Biochemistry / Q000379:methods*; D060326:Chemistry Techniques, Synthetic; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D011130:RNA Ligase (ATP) / Q000737:chemistry; D012344:RNA, Transfer, Ala / Q000138:chemical synthesis / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry
chemical_list: D012344:RNA, Transfer, Ala; D014764:Viral Proteins; D005461:Fluorine; D011130:RNA Ligase (ATP); C467724:bacteriophage T4 RNA ligase 2
keywords: aminoacyl-tRNAs; dinucleotides; fluoro-nucleosides; peptidoglycan; tRNA; transferases