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Synthesis and Incorporation of k 2 U into RNA
Author(s) -
Nainyte Milda,
Carell Thomas
Publication year - 2020
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.202000016
Subject(s) - chemistry , phosphoramidite , tautomer , rna , cytidine , stereochemistry , base pair , nucleoside , pyrimidine , amino acid , context (archaeology) , oligonucleotide , biochemistry , dna , gene , biology , paleontology , enzyme
Lysidine (k 2 C) is one of the most modified pyrimidine RNA bases. It is a cytidine nucleoside, in which the 2‐oxo functionality of the heterocycle is replaced by the ϵ ‐amino group of the amino acid lysine. As such, lysidine is an amino acid‐containing RNA nucleoside that combines directly genotype (C‐base) with phenotype (lysine amino acid). This makes the compound particularly important in the context of theories about the origin of life and here especially for theories that target the origin of translation. Here, we report the total synthesis of the U‐derivative of lysidine (k 2 U), which should have the same base pairing characteristics as k 2 C if it exists in the isoC‐like tautomeric form. To investigate this question, we developed a phosphoramidite building block for k 2 U, which allows its incorporation into RNA strands. Within RNA, k 2 U can base pair with the counter base U and isoG, confirming that k 2 U prefers an isoC‐like tautomeric structure that is also known to dominate for k 2 C. The successful synthesis of a k 2 U phosphoramidite and its use for RNA synthesis now paves the way for the preparation of a k 2 C phosphoramidite and RNA strands containing k 2 C.