Synthesis of Galactosyl-Queuosine and Distribution of Hypermodified Q-Nucleosides in Mouse Tissues


Peter Thumbs, Timm T. Ensfelder, Markus Hillmeier, Mirko Wagner, Matthias Heiss, Constanze Scheel, Alexander Schön, Markus Müller, Stylianos Michalakis, Stefanie Kellner, and Thomas Carell

Angew. Chem. Int. Ed., 2020, 59, 1 – 6

Queuosine (Q) is a hypermodified RNA nucleoside that is found in tRNAHis, tRNAAsn, tRNATyr, and tRNAAsp. It is located at the wobble position of the tRNA anticodon loop, where it can interact with U as well as C bases located at the respective position of the corresponding mRNA codons. In tRNATyr and tRNAAsp of higher eukaryotes, including humans, the Q base is for yet unknown reasons further modified by the addition of a galactose and a mannose sugar, respectively. The reason for this additional modification, and how the sugar modification is orchestrated with Q formation and insertion, is unknown. Here, we report a total synthesis of the hypermodified nucleoside galactosyl‐queuosine (galQ). The availability of the compound enabled us to study the absolute levels of the Q‐family nucleosides in six different organs of newborn and adult mice, and also in human cytosolic tRNA. Our synthesis now paves the way to a more detailed analysis of the biological function of the Q‐nucleoside family.