A1 Refereed original research article in a scientific journal
Solid-Supported 2 '-O-Glycoconjugation of Oligonucleotides by Azidation and Click Reactions
Authors: Anu Kiviniemi, Pasi Virta, Mikhail S Drenichev, Sergey N Mikhailov, Harri Lönnberg
Publisher: AMER CHEMICAL SOC
Publication year: 2011
Journal: Bioconjugate Chemistry
Journal name in source: BIOCONJUGATE CHEMISTRY
Journal acronym: BIOCONJUGATE CHEM
Volume: 22
Issue: 6
First page : 1249
Last page: 1255
Number of pages: 7
ISSN: 1043-1802
DOI: https://doi.org/10.1021/bc200097g(external)
Abstract
2'-O-[(2-Bromoethoxy)methyl]cytidine and 2'-O-[(2-azidoethoxy)methyl]cytidine have been prepared and introduced as appropriately protected 3'-phosphoramidite (1) and 3'-(H-phosphonate) (2) building blocks, respectively, into 2'-O-methyl oligoribonucleotides. The support-bound oligonucleotides were subjected to two consecutive conjugations with alkynyl-functionalized monosaccharides. The first saccharide was introduced by a Cu(I) promoted click reaction with 2 and the second by azidation of the 2-bromoethoxy group of 1 followed by the click reaction. The influence of the 2'-glycoconjugations on hybridization with DNA and 2'-O-methyl RNA targets was studied. Two saccharide units within a 15-mer oligonucleotide had a barely noticeable effect on the duplex stability, while introduction of a third one moderately decreased the melting temperature.
2'-O-[(2-Bromoethoxy)methyl]cytidine and 2'-O-[(2-azidoethoxy)methyl]cytidine have been prepared and introduced as appropriately protected 3'-phosphoramidite (1) and 3'-(H-phosphonate) (2) building blocks, respectively, into 2'-O-methyl oligoribonucleotides. The support-bound oligonucleotides were subjected to two consecutive conjugations with alkynyl-functionalized monosaccharides. The first saccharide was introduced by a Cu(I) promoted click reaction with 2 and the second by azidation of the 2-bromoethoxy group of 1 followed by the click reaction. The influence of the 2'-glycoconjugations on hybridization with DNA and 2'-O-methyl RNA targets was studied. Two saccharide units within a 15-mer oligonucleotide had a barely noticeable effect on the duplex stability, while introduction of a third one moderately decreased the melting temperature.
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