O4-Thymidinyl functionalization to a solid support enables a versatile 3′-end oligonucleotide conjugation strategy† † In memory of Professor Marcel Schlaf
- 1Department of Chemistry, University of Guelph 50 Stone Rd. E Guelph N1G 2W1 ON Canada [email protected].
Abstract
Conjugation of ligands to oligonucleotides represents an effective strategy for modulating and enhancing the physicochemical and biological properties of nucleic acids, including cellular uptake and delivery, bioavailability, and capabilities for detection and tracking. Here, we report a straightforward conjugation methodology from a readily accessible unit containing a 3'-azido functional group and an alkylene linker from the O ⁴-position of a thymidinyl unit to a solid support. We showcase that this unit is compatible with efficient post-elongation on-column strain-promoted azide-alkyne cycloaddition (SPAAC) chemistry. Alternatively, it may be efficiently reduced to the corresponding amino group on-solid support, allowing for a variety of amidation reactions with model ligand handles. We show compatibility with both DNA and RNA. Ultimately, our newly developed strategy consists of a unified unit capable of pre- and post-strand assembly conjugation, and will find applications in multiple (bio)conjugation contexts.
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BibTeX
@article{horton2026o4thymidinyl,
title = {{O4-Thymidinyl functionalization to a solid support enables a versatile 3′-end oligonucleotide conjugation strategy† † In memory of Professor Marcel Schlaf}},
author = {Nicholas G Horton and Evan Zakaria and Dara V Grebennikova and Derek K O'Flaherty},
journal = {RSC advances},
year = {2026},
month = nov,
doi = {10.1039/d6ra06451e},
url = {https://europepmc.org/article/PMC/PMC13726092},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - O4-Thymidinyl functionalization to a solid support enables a versatile 3′-end oligonucleotide conjugation strategy† † In memory of Professor Marcel Schlaf
AU - Nicholas G Horton
AU - Evan Zakaria
AU - Dara V Grebennikova
AU - Derek K O'Flaherty
PY - 2026
DA - 2026/11/02
JO - RSC advances
DO - 10.1039/d6ra06451e
UR - https://europepmc.org/article/PMC/PMC13726092
AB - Conjugation of ligands to oligonucleotides represents an effective strategy for modulating and enhancing the physicochemical and biological properties of nucleic acids, including cellular uptake and delivery, bioavailability, and capabilities for detection and tracking. Here, we report a straightforward conjugation methodology from a readily accessible unit containing a 3'-azido functional group and an alkylene linker from the O ⁴-position of a thymidinyl unit to a solid support. We showcase that this unit is compatible with efficient post-elongation on-column strain-promoted azide-alkyne cycloaddition (SPAAC) chemistry. Alternatively, it may be efficiently reduced to the corresponding amino group on-solid support, allowing for a variety of amidation reactions with model ligand handles. We show compatibility with both DNA and RNA. Ultimately, our newly developed strategy consists of a unified unit capable of pre- and post-strand assembly conjugation, and will find applications in multiple (bio)conjugation contexts.
SN - 2046-2069
ER -