Enabling Multiple Conjugation to Oligonucleotides Using "Click Cycles".
Bioconjug Chem
; 27(11): 2620-2628, 2016 Nov 16.
Article
em En
| MEDLINE
| ID: mdl-27756130
ABSTRACT
An efficient method for the synthesis of multiply functionalized oligonucleotides (ONs) utilizing a novel H-phosphonate alkyne-based linker for multiple functionalization (LMF) is developed. The strategy allows for the conjugation of various active entities to oligonucleotide through the postsynthetic attachment of LMF at the 5'-terminus of ONs using H-phosphonate chemistry followed by conjugation of various entities via [3 + 2] copper(I) catalyzed cycloaddition in a stepwise manner. Each cycle is composed of attachment of the LMF followed by a click reaction with azido-containing units. Sequential solid-phase synthesis of oligonucleotide conjugates containing three attached entities was performed using an acetylated form of MIF peptide conjugated to azido linker, achieving high conversions at each unit addition. In addition, to show the versatility of the method, oligonucleotide conjugates with several different classes of compounds were synthesized. Each conjugate containing three different entities, whose structure and function varied (e.g., sugars, peptides, fluorescent labels, and m3G-Caps).
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Base de dados:
MEDLINE
Assunto principal:
Oligonucleotídeos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article