A1 Refereed original research article in a scientific journal
Synthesis of Oligonucleotide Glycoconjugates Using Sequential Click and Oximation Ligations
Authors: Karskela M, Helkearo M, Virta P, Lonnberg H
Publisher: AMER CHEMICAL SOC
Publication year: 2010
Journal: Bioconjugate Chemistry
Journal name in source: BIOCONJUGATE CHEMISTRY
Journal acronym: BIOCONJUGATE CHEM
Number in series: 4
Volume: 21
Issue: 4
First page : 748
Last page: 755
Number of pages: 8
ISSN: 1043-1802
DOI: https://doi.org/10.1021/bc900529g
Abstract
Oligodeoxyribonucleotide glycoconjugates bearing two trivalent glycoclusters have been synthesized by two alternative methods based on solid-supported oximation of aminooxy functionalized oligonueleotides with glycoclusters constructed by click chemistry. In more detail, the trivalent glycoclusters (5 and 6) bearing three sugar pendants were first assembled by treating a 4-[tri-O-propargylpentaerythrityloxy]benzaklehyde scaffold with methyl 6-azido-6-deoxyglycopyranoside under the click reaction conditions. Two phosphoramidite reagents containing a phthaloyl protected aminooxy function, viz., 2-cyanoethyl N,N-diisopropylphosphoramidites derived from 3[3,5-bis(phthalimidoxymethyl)phenoxy]propanol (12) and 5-(4,4'-dimethoxytrity1)-1,2-dideoxy-1-C-(2-phthalimidoxyethyl)-beta-D-erythro-pentofuranose (16), were synthesized and incorporated as branching units in appropriate places of the oligonucleotide chains. On using 12, the phthaloyl protections of the branching unit were removed and two identical glycoclusters were attached via oxime linkage to the 5'-terminus of the support-bound oligonucleotide chain. With branching unit 16, the phosphoramidite coupling and the oximation were carried out alternately, allowing introduction of two dissimilar trivalent glycoclusters close to the 3'-end of the oligonucleotide chain. The products (20, 26) were released and deprotected by ammonolysis and purified by HPLC chromatography.
Oligodeoxyribonucleotide glycoconjugates bearing two trivalent glycoclusters have been synthesized by two alternative methods based on solid-supported oximation of aminooxy functionalized oligonueleotides with glycoclusters constructed by click chemistry. In more detail, the trivalent glycoclusters (5 and 6) bearing three sugar pendants were first assembled by treating a 4-[tri-O-propargylpentaerythrityloxy]benzaklehyde scaffold with methyl 6-azido-6-deoxyglycopyranoside under the click reaction conditions. Two phosphoramidite reagents containing a phthaloyl protected aminooxy function, viz., 2-cyanoethyl N,N-diisopropylphosphoramidites derived from 3[3,5-bis(phthalimidoxymethyl)phenoxy]propanol (12) and 5-(4,4'-dimethoxytrity1)-1,2-dideoxy-1-C-(2-phthalimidoxyethyl)-beta-D-erythro-pentofuranose (16), were synthesized and incorporated as branching units in appropriate places of the oligonucleotide chains. On using 12, the phthaloyl protections of the branching unit were removed and two identical glycoclusters were attached via oxime linkage to the 5'-terminus of the support-bound oligonucleotide chain. With branching unit 16, the phosphoramidite coupling and the oximation were carried out alternately, allowing introduction of two dissimilar trivalent glycoclusters close to the 3'-end of the oligonucleotide chain. The products (20, 26) were released and deprotected by ammonolysis and purified by HPLC chromatography.
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