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Prakash, Thazha P.; Brad Wan, W.; Low, Audrey; Yu, Jinghua; Chappell, Alfred E.; Gaus, Hans; Kinberger, Garth A.; Østergaard, Michael E.; Migawa, Michael T.; Swayze, Eric E.; Seth, Punit P.
Bioorganic & medicinal chemistry letters, 10/2015, Letnik: 25, Številka: 19Journal Article
Display omitted A convenient solid-phase synthetic method was developed for assembling a triantennary N-acetylgalactosamine (GalNAc) cluster on the 5′-end of antisense oligonucleotide using phosphoramidite chemistry. Conjugation of the 5′-triantennary GalNAc cluster improved potency of the 14 mer ASO 7-fold in mice and more than 50 fold in hepatocytes. The synthetic approach described in this Letter simplifies the synthesis of 5′-triantennary GalNAc cluster conjugated ASOs and helps understand the structure–activity relationship for targeting hepatocytes with oligonucleotide therapeutics.
