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Synthesis of Monovalent N-Acetylgalactosamine Phosphoramidite for Liver-Targeting Oligonucleotides.
- Source :
-
Current protocols in nucleic acid chemistry [Curr Protoc Nucleic Acid Chem] 2019 Sep; Vol. 78 (1), pp. e99. - Publication Year :
- 2019
-
Abstract
- Ligand-targeted drug delivery (LTDD) has emerged as an attractive option in the field of oligonucleotide drugs following the great success of N-acetylgalactosamine (GalNAc)-conjugated siRNA and antisense oligonucleotides. GalNAc is a well-known ligand of the asialoglycoprotein receptor (ASGPR), and is classified as a C-type lectin associated with the metabolism of desialylated glycoproteins. This article describes the synthesis of a non-nucleosidic monovalent GalNAc phosphoramidite-a useful reagent for facilitating the conjugation of GalNAc epitopes into oligonucleotides using DNA synthesizers-together with some important caveats. The monomeric GalNAc consists of three parts: (1) a GalNAc moiety, (2) a linker moiety, and (3) a trans-4-hydroxyprolinol (tHP) branch point. The GalNAc moiety and the tHP moiety are coupled via a condensation reaction to prepare the monovalent GalNAc phosphoramidite. © 2019 by John Wiley & Sons, Inc. Basic Protocol 1: Synthesis of N-acetylgalactosamine ligand Basic Protocol 2: Preparation of trans-4-hydroxyprolinol building block Basic Protocol 3: Preparation of GalNAc phosphoramidite.<br /> (© 2019 John Wiley & Sons, Inc.)
Details
- Language :
- English
- ISSN :
- 1934-9289
- Volume :
- 78
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Current protocols in nucleic acid chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 31529782
- Full Text :
- https://doi.org/10.1002/cpnc.99