Solid-phase synthesis of multiantennary oligonucleotide glycoconjugates utilizing on-support oximation.
A novel method for preparation of multivalent oligonucleotide glycoconjugates on a solid support has been described. A pentaerythritol-based phosphoramidite (1) bearing two masked aminooxy groups has been used as the key building block. After conventional chain assembly, the aminooxy functions have been deblocked by a hydrazinium acetate treatment and subsequently oximated with fully acetylated 4-oxobutyl alpha-D-mannopyranoside. The conjugates obtained have been shown to withstand standard ammonolytic deprotection and cleavage from the support. Four different oligonucleotide glycoconjugates containing two, four, or six alpha-D-mannopyranosyl units (12-15) have been prepared to demonstrate the applicability of the procedure. The glycosyl residues only moderately retards hybridization of the oligonucleotide moiety.
Katajisto
Johanna
J
Department of Chemistry, University of Turku, FIN-20014, Finland. jokrka@utu.fi
Virta
Pasi
P
Lönnberg
Harri
H
D002851:Chromatography, High Pressure Liquid; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D008358:Mannose / Q000737:chemistry; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013696:Temperature
D006001:Glycoconjugates; D008024:Ligands; D009841:Oligonucleotides; D009943:Organophosphorus Compounds; C434331:phosphoramidite; D008358:Mannose