title: Synthesis of aminoacylated N(6),N(6)-dimethyladenosine solid support for efficient access to hydrolysis-resistant 3'-charged tRNA mimics.
abstract: RNA-amino acid and RNA-peptide conjugates that mimic charged tRNA 3'-ends are valuable substrates for structural and functional investigations of ribosomal complexes. To obtain such conjugates, most synthetic approaches that are found in the literature make use of puromycin. This well available aminonucleoside antibiotic contains a dimethylamino group at the nucleobase and a methylated tyrosine that is connected via an amide linkage to the ribose moiety. To increase structural diversity, we present the synthesis of a N(6),N(6)-dimethylated 3'-azido-3'-deoxyadenosine precursor that can be coupled to any amino acid. Further derivatization results in the solid support that is eligible for the preparation of stable 3'-aminoacyl- or 3'-peptidyl-tRNA termini with an amide instead of the natural ester linkage. The present work expands our previously established route that delivered a broad range of peptidyl-tRNA mimics to the corresponding counterparts with N(6),N(6)-dimethylation pattern of the terminal adenosine (A76). This aspect is of significance to modulate the binding preferences of the mimics for ribosomal A- versus P-site.
authors.affiliation: Institute of Organic Chemistry and Center for Molecular Biosciences, CMBI, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria.
authors.forename: Sandro
authors.initials: S
authors.lastname: Neuner
authors.affiliation: Institute of Organic Chemistry and Center for Molecular Biosciences, CMBI, University of Innsbruck, Innrain 80-82, 6020 Innsbruck, Austria. Electronic address: ronald.micura@uibk.ac.at.
authors.forename: Ronald
authors.initials: R
authors.lastname: Micura
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006868:Hydrolysis; D018716:Molecular Mimicry; D012346:RNA, Transfer, Amino Acyl / Q000737:chemistry*; D012270:Ribosomes / Q000378:metabolism; D060327:Solid-Phase Synthesis Techniques
chemical_list: D012346:RNA, Transfer, Amino Acyl; C019037:tRNA, peptidyl-; C021013:N(6),N(6)-dimethyladenosine; D000241:Adenosine
keywords: Azide; Bioconjugates; Nucleosides; Oligonucleotide synthesis; Ribosomes; Trimethyllysine