Next Article in Journal
Lactose Binding Induces Opposing Dynamics Changes in Human Galectins Revealed by NMR-Based Hydrogen–Deuterium Exchange
Next Article in Special Issue
High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents
Previous Article in Journal
Synthesis and Physicochemical Characterization of the Process-Related Impurities of Eplerenone, an Antihypertensive Drug
Previous Article in Special Issue
Oligonucleotides and ND-FISH Displaying Different Arrangements of Tandem Repeats and Identification of Dasypyrum villosum Chromosomes in Wheat Backgrounds
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessCommunication
Molecules 2017, 22(8), 1356;

Synthesis of 5′-GalNAc-Conjugated Oligonucleotides: A Comparison of Solid and Solution-Phase Conjugation Strategies

Ionis Pharmaceuticals, Inc., Carlsbad, CA 92010, USA
Author to whom correspondence should be addressed.
Received: 11 July 2017 / Revised: 7 August 2017 / Accepted: 10 August 2017 / Published: 15 August 2017
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
Full-Text   |   PDF [1842 KB, uploaded 15 August 2017]   |  


Antisense 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
Keywords: oligonucleotide; GalNAc; conjugate oligonucleotide; GalNAc; conjugate

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top