A convenient synthesis of 5′-triantennary N-acetyl-galactosamine clusters based on nitromethanetrispropionic acid. Issue 9 (1st May 2016)

• Record Type: Journal Article
• Authors: Migawa, Michael T.; Prakash, Thazha P.; Vasquez, Guillermo; Wan, W. Brad; Yu, Jinghua; Kinberger, Garth A.; Østergaard, Michael E.; Swayze, Eric E.; Seth, Punit P.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 9(2016)
• Page Start: 2194
• Page End: 2197
• Publication Date: 2016-05-01
• Subjects: Nucleic acid -- Conjugate -- Synthesis -- GalNAc; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.070
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A convenient method for the synthesis of several triantennary GalNAc clusters based on a nitromethanetrispropionic acid core was developed. The synthetic approach involves pentafluorophenolic ester intermediates which can be used in a one-pot, seven reaction procedure to quickly prepare a variety of triantennary GalNAc conjugated ASOs. The GalNAc clusters were conjugated to the 5′-end of an antisense oligonucleotide and evaluated for activity in primary mouse hepatocytes where they showed ∼10-fold improvement in activity.