Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions
| Autor: | Edward C. Sherer, Zhen Li, Daniel Zewge, Gabor Butora, Ian W. Davies, Joseph D. Armstrong, Greg Copeland, David M. Tellers, Joseph R. Gouker, Daniel R. Sidler, Vasant Jadhav |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Azides Acetylgalactosamine Biomedical Engineering Triazole Oligonucleotides Pharmaceutical Science Bioengineering 010402 general chemistry 01 natural sciences Catalysis 03 medical and health sciences chemistry.chemical_compound Amide Humans RNA Small Interfering Pharmacology Cycloaddition Reaction Esterification Oligonucleotide Organic Chemistry Triazoles Combinatorial chemistry Amides Cycloaddition 0104 chemical sciences 030104 developmental biology chemistry Propargyl Click Chemistry Nucleoside Copper Biotechnology Conjugate HeLa Cells |
| Zdroj: | Bioconjugate chemistry. 29(6) |
| ISSN: | 1520-4812 |
| Popis: | An efficient multicomponent orthogonal protocol was developed for post-synthetic oligonucleotide modification using commercially available 2'- O-methyl ester and 2'- O-propargyl nucleoside scaffolds. Amidation of methyl esters with primary amines was achieved in the presence of 2'-propargyl groups which were utilized for subsequent copper catalyzed cycloaddition with GalNAc-azide. The methodology was applied to generate siRNA composed of multiple amide and triazole conjugates. Computational methods were used to illustrate the impact of substitution at the 2'-position. This a powerful post-oligomerization technique for rapidly introducing diversity to oligonucleotide design. |
| Databáze: | OpenAIRE |
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