Solid-phase synthesis of multiantennary oligonucleotide glycoconjugates utilizing on-support oximation

Area of Science:

• Carbohydrate Chemistry
• Oligonucleotide Synthesis
• Bioconjugation

Background:

• Multivalent oligonucleotide glycoconjugates are valuable tools in chemical biology and diagnostics.
• Previous methods for synthesizing these complex molecules on solid supports have limitations.

Purpose of the Study:

• To develop a novel and efficient solid-phase method for preparing multivalent oligonucleotide glycoconjugates.
• To demonstrate the versatility of the method by synthesizing conjugates with varying numbers of glycosyl residues.

Main Methods:

• Utilized a novel pentaerythritol-based phosphoramidite building block with masked aminooxy groups.
• Employed conventional solid-phase oligonucleotide synthesis followed by deblocking and oximation with a mannoside derivative.
• Assessed the stability of the resulting glycoconjugates during deprotection and cleavage from the solid support.

Main Results:

• Successfully prepared four different oligonucleotide glycoconjugates with two, four, or six alpha-D-mannopyranosyl units.
• The synthesized glycoconjugates demonstrated stability under standard deprotection and cleavage conditions.
• The presence of glycosyl residues exhibited only a moderate effect on the hybridization properties of the oligonucleotide.

Conclusions:

• The described method provides an efficient route for the solid-phase synthesis of multivalent oligonucleotide glycoconjugates.
• The procedure is robust and yields stable conjugates suitable for further applications.
• These findings open avenues for the development of novel diagnostic and therapeutic agents based on oligonucleotide-carbohydrate interactions.