Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies
AbstractAntisense oligonucleotides (ASOs) conjugated to triantennary N-acetyl galactosamine (GalNAc) ligands represent an emerging approach to antisense therapy. Our current generation of GalNAc-ASO conjugates link the GalNAc to the 5′-terminus of the ASO. The conjugation reaction can be accomplished using solution-phase or solid-phase techniques. Here we show a direct comparison of a solution-phase and a solid-phase conjugation strategy. The solution-phase approach, using amine-pentafluorophenyl (PFP) ester coupling, is higher yielding and gives material of slightly higher purity, but requires several additional unit operations and longer production time. The solid-phase approach, using a protected GalNAc ligand phosphoramidite, is more expedient, but results in lower yield and purity. Both strategies efficiently deliver conjugated material in excellent purity. View Full-Text
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Cedillo, I.; Chreng, D.; Engle, E.; Chen, L.; McPherson, A.K.; Rodriguez, A.A. Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies. Molecules 2017, 22, 1356.
Cedillo I, Chreng D, Engle E, Chen L, McPherson AK, Rodriguez AA. Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies. Molecules. 2017; 22(8):1356.Chicago/Turabian Style
Cedillo, Isaiah; Chreng, Dana; Engle, Elyse; Chen, Lijian; McPherson, Andrew K.; Rodriguez, Andrew A. 2017. "Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies." Molecules 22, no. 8: 1356.
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