Synthesis of stable aminoacyl-tRNA analogs.

摘要: Aminoacyl-tRNAs have important roles in a variety of biological processes. Here, we describe the synthesis stable aminoacyl-tRNA analogs containing 1,4-substituted 1,2,3-triazole rings. The procedure involves (i) copper-catalyzed cycloadditions 3′-or 2′-azido-adenosine and alkynes, (ii) coupling between resulting triazole-deoxyadenosine derivatives deoxycytidine phosphoramidite, (iii) enzymatic ligation 2′- or 3′-triazole-dinucleotides with 22-nt RNA microhelix that mimics acceptor arm tRNA. Each nucleoside nucleotide intermediate was characterized by MS spectrometry 1H, 31P, 13C NMR spectroscopy, tRNA-analogs were assayed for inhibition FemXWv, an alanyl-transferase essential formation peptidoglycan network Gram-positive bacterial pathogens. low IC50 values obtained (2 to 4 µM) indicate five-membered triazole rings acted as isosteres esters can be used design analogs. Curr. Protoc. Nucleic Acid Chem. 44:4.44.1-4.44.33. © 2011 John Wiley & Sons, Inc. Keywords: aminoacyl-tRNA; click chemistry; dinucleotides; inhibitors; triazoles; azidoadenosine; transferase