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Chemical Synthesis of Oligoribonucleotide (ASL of tRNA Lys T. brucei ) Containing a Recently Discovered Cyclic Form of 2‐Methylthio‐ N 6 ‐threonylcarbamoyladenosine (ms 2 ct 6 A)
Author(s) -
Debiec Katarzyna,
Matuszewski Michal,
Podskoczyj Karolina,
Leszczynska Grazyna,
Sochacka Elzbieta
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201902411
Subject(s) - transfer rna , guanosine , oligonucleotide , stereochemistry , chemistry , nucleoside , monomer , phosphoramidite , rna , biochemistry , dna , organic chemistry , gene , polymer
The synthesis of the protected form of 2‐methylthio‐ N 6 ‐threonylcarbamoyl adenosine ( ms 2 t 6 A) was developed starting from adenosine or guanosine by using the optimized carbamate method and, for the first time, an isocyanate route. The hypermodified nucleoside was subsequently transformed into the protected ms 2 t 6 A ‐phosphoramidite monomer and used in a large‐scale synthesis of the precursor 17nt ms 2 t 6 A ‐oligonucleotide (the anticodon stem and loop fragment of tRNA Lys from T. brucei ). Finally, stereochemically secure ms 2 t 6 A → ms 2 ct 6 A cyclization at the oligonucleotide level efficiently afforded a tRNA fragment bearing the ms 2 ct 6 A unit. The applied post‐synthetic approach provides two sequentially homologous ms 2 t 6 A ‐ and ms 2 ct 6 A ‐oligonucleotides that are suitable for further comparative structure–activity relationship studies.