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DOI: 10.1055/s-0042-1751405
Benzo-Fused 7-Oxabicyclo[2.2.1]heptane-2,3-diol Derivatives as Universal Linkers for Solid-Phase Oligonucleotide Synthesis
K.Y. acknowledges a Nagai Memorial Research Scholarship from the Pharmaceutical Society of Japan.
Abstract
In solid-phase oligonucleotide (ON) synthesis, especially for 3′-modified ONs, a universal linker attached to a solid support is widely used. In this study, benzo-fused 7-oxabicyclo[2.2.1]heptane-2,3-diol derivatives are designed, synthesized, and evaluated as universal linkers. The designed linkers show reactivity comparable to that of a conventional universal linker for releasing the desired ONs. Additionally, these materials exhibit a more robust structure under basic conditions, as generally used in ON synthesis, and hydrophobic properties relative to the conventional universal linker. Notably, when diphenyl-substituted (terphenyl) and phenanthrene-type (PT) linkers are used, cyclic phosphodiesters derived from linker units as byproducts, which are produced by release of ONs from the linker units, are detected in the HPLC chromatograms. The PT linker is applicable to various ON syntheses using controlled pore glass (CPG) and polystyrene (PS) resins. These results demonstrate that the PT linker can serve as an alternative to conventional universal linkers.
Key words
solid-phase synthesis - universal linker - oligonucleotides - benzo-fused 7-oxabicyclo[2.2.1]heptane-2,3-diol - phenanthreneSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0042-1751405.
- Supporting Information
Publication History
Received: 18 October 2022
Accepted after revision: 12 December 2022
Article published online:
12 January 2023
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