Synthesis of oligonucleotide glycoconjugates using sequential click and oximation ligations

Area of Science:

• Organic Chemistry
• Bioconjugation Chemistry
• Oligonucleotide Synthesis

Background:

• Oligonucleotide glycoconjugates combine nucleic acid properties with carbohydrate functions.
• Developing efficient methods for attaching multiple carbohydrate moieties to oligonucleotides is crucial for creating novel biomaterials.

Purpose of the Study:

• To synthesize oligonucleotide glycoconjugates featuring two trivalent glycoclusters.
• To explore two alternative synthetic routes for constructing these complex molecules.

Main Methods:

• Solid-supported oximation of aminooxy-functionalized oligonucleotides.
• Click chemistry for assembling trivalent glycoclusters.
• Synthesis of novel phosphoramidite reagents with protected aminooxy groups.

Main Results:

• Successful synthesis of oligonucleotide glycoconjugates bearing two trivalent glycoclusters via two distinct pathways.
• Demonstrated control over the attachment of identical or dissimilar glycoclusters to specific oligonucleotide positions (5'-terminus or near 3'-end).
• Purification of the final products using HPLC chromatography.

Conclusions:

• The developed methods provide versatile strategies for creating complex oligonucleotide glycoconjugates.
• The synthetic approaches allow for precise control over the number and type of glycoclusters attached.
• These glycoconjugates hold potential for applications in diagnostics, therapeutics, and nanotechnology.