title: Synthesis of stable aminoacyl-tRNA analogs.
abstract: Aminoacyl-tRNAs have important roles in a variety of biological processes. Here, we describe the synthesis of stable aminoacyl-tRNA analogs containing 1,4-substituted 1,2,3-triazole rings. The procedure involves (i) copper-catalyzed cycloadditions of 3'-or 2'-azido-adenosine and alkynes, (ii) coupling between the resulting triazole-deoxyadenosine derivatives and a deoxycytidine phosphoramidite, and (iii) the enzymatic ligation of the 2'- or 3'-triazole-dinucleotides with a 22-nt RNA microhelix that mimics the acceptor arm of tRNA. Each nucleoside and nucleotide intermediate was characterized by MS spectrometry and (1)H, (31)P, and (13)C NMR spectroscopy, and the tRNA-analogs were assayed for inhibition of FemXWv, an alanyl-transferase essential for the formation of the peptidoglycan network of Gram-positive bacterial pathogens. The low IC(50) values obtained (2 to 4 µM) indicate that the five-membered triazole rings acted as an isosteres of esters and can be used for the design of stable aminoacyl-tRNA analogs.
authors.affiliation: Institut Parisien de Chimie Moléculaire, Université Pierre et Marie Curie, Paris, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Chemama
authors.forename: Matthieu
authors.initials: M
authors.lastname: Fonvielle
authors.forename: Maxime
authors.initials: M
authors.lastname: Lecerf
authors.forename: Dénia
authors.initials: D
authors.lastname: Mellal
authors.forename: Hélène
authors.initials: H
authors.lastname: Fief
authors.forename: Michel
authors.initials: M
authors.lastname: Arthur
authors.forename: Mélanie
authors.initials: M
authors.lastname: Etheve-Quelquejeu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis; D012346:RNA, Transfer, Amino Acyl / Q000138:chemical synthesis* / Q000737:chemistry; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014166:Transferases / Q000037:antagonists & inhibitors; D014230:Triazoles / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D012346:RNA, Transfer, Amino Acyl; D014230:Triazoles; D014166:Transferases