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Novel Dioxane and Morpholino Nucleotide Analogues: Syntheses and RNA‐Hybridization Properties
Author(s) -
Hofmeister Armin,
JahnHofmann Kerstin,
Krack Arne,
Müller Armin,
Kurz Michael,
Scheidler Sabine
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202000693
Subject(s) - morpholine , nucleotide , chemistry , diastereomer , oligonucleotide , stereochemistry , combinatorial chemistry , derivatization , ring (chemistry) , rna , chirality (physics) , dna , organic chemistry , biochemistry , nambu–jona lasinio model , high performance liquid chromatography , chiral symmetry breaking , physics , quantum mechanics , gene , quark
A novel class of nucleotide analogues with a dioxane ring as central scaffold has been developed. Synthetic routes in two diastereomeric series were realized, and the final thymidine analogues were synthesized with common functionalities for the automated oligonucleotide synthesis. The chemical space of the initially derived nucleotides was expanded by changing the central dioxane to analogous morpholine derivatives. This opens up the possibility for further derivatization by attaching different substituents at the morpholine nitrogen. The novel nucleotide building blocks were incorporated into double‐stranded RNA sequences, and their hybridization properties investigated by melting‐temperature analysis. Both scaffolds, dioxanes and morpholines, had an equal impact on double‐strand stability, but T m values differed depending on the chirality in the six‐membered ring.