RESUMO
Universal solid supports are widely used in solid-phase oligonucleotide (ON) synthesis based on phosphoramidite chemistry. Herein, we describe the synthesis of hydrophobic universal linkers, namely phenanthrene ring-fused 7-oxabicyclo[2.2.1]heptane-2,3-diol derivatives (PT linkers), their coupling to solid supports [e.g., controlled pore glass (CPG) and polystyrene (PS)], and the use of the resulting PT-linker-modified solid supports in ON synthesis. PT linkers were synthesized in four steps from commercial materials and subsequently attached to CPG and PS resins through succinyl and diethylene glycol-containing spacers, respectively. Cleavage of the desired ON from the resins was accomplished under standard basic conditions, indicating that the reactivity of the PT linkers was comparable to that of conventional universal linkers. Furthermore, owing to their high hydrophobicity, the desired ON could be readily separated from impurities originating from the PT linker by reversed phase HPLC. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Synthesis of phenanthrene ring-fused 7-oxabicyclo[2.2.1]heptane-2,3-diol (PT linker) derivatives Basic Protocol 2: Preparation of PT-linker-modified CPG and PS resins Basic Protocol 3: Solid-phase ON synthesis using PT-linker-modified solid supports and cleavage of ONs from resins.