Post-Synthetic Modification of Oligonucleotides via Orthogonal Amidation and Copper Catalyzed Cycloaddition Reactions.
Bioconjug Chem
; 29(6): 1859-1865, 2018 06 20.
Article
em En
| MEDLINE
| ID: mdl-29893553
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
/
Acetilgalactosamina
/
Azidas
/
Cobre
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RNA Interferente Pequeno
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Reação de Cicloadição
/
Amidas
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article